A DISSERTATION TITLED

THE PREVALENCE OF ATOPIC DERMATITIS IN A

DERMATOLOGY CLINIC IN KADUNA, KADUNA STATE, NIGERIA,

SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENT

FOR THE AWARD OF THE FELLOWSHIP IN FAMILY MEDICINE OF

THE NATIONAL POSTGRADUATE MEDICAL COLLEGE OF

NIGERIA (FMCFM) NOVEMBER 2006

BY

DR MIJINYAWA DUGURI IBRAHIM MBBS UNIJOS 1994

AT

44 NIGERIAN ARMY REFERENCE HOSPITAL, KADUNA

2

DECLARATION

I solemnly declare that this dissertation was carried out by me and has not been submitted to

another examining board or for publication in any journals.

Dr. Mijinyawa D. Ibrahim

3

CERTIFICATION

We certify that this dissertation by Dr Mijinyawa D. Ibrahim was conducted by him at Barau

Dikko Specialist Hospital, Kaduna under our direct supervision.

Col LA Moses FMCGP, FWACP.

Chief Consultant Family Physician

44 Nigerian Army Reference Hospital, Kaduna.

Dr Husain Yahya Msc, FMCP.

Consultant Physician and Dermatologist

Barau Dikko Specialist Hospital, Kaduna.

4

DEDICATION

This book is dedicated to all patients with Atopic Dermatitis wherever they are, especially

children who suffer in silence and their parents who continue to try all forms of alternative

medications in order to free them from the burden of this mysterious disease.

5

ACKNOWLEDGMENT

I would like to express my profound gratitude to Col (Dr) Akin Moses for his thoroughness as

a trainer. I found his wealth of experience and dedication as a wonderful source of inspiration

forever. I also would like to express my gratitude to Dr Husain Yahya for introducing me to the

world of Dermatology. The materials he gave to me would remain an asset forever.

My warm thanks go to Brig Gen Matthew for accepting the resident doctors aspirations and

making it possible for them to commence the residency programme in 44 Nigerian Army

Reference Hospital, Kaduna. Special thanks to Maj Gen BE Abang and Brig Gen HMA Agada

who continue to provide an environment conducive for residency training in 44 NARHK. I will

also like to remember late Major General Ahmadu Rimi for being a father who stood for us

when the building was about to collapsed, may his soul rest in peace.

I will also like to say thank you to the management of Barau Dikko Specialist Hospital, Kaduna

for granting me the permission to conduct this study in their hospital.

I would like to acknowledge the valuable information at the beginning by my cousin Dr Idris

Baba, and my uncle Alhaji Bala Duguri for supporting me with a laptop computer.

I must not conclude without a special mention of my parents and brothers. The same goes to

my wife and daughter Fatima for their understanding and love during these periods that I was

up and about.

6

TABLE OF CONTENTS

Page

Title page i

Declaration ii

Certification iii

Dedication iv

Acknowledgement v

Table of contents vi

List of tables vii

List of figures viii

List of pictures ix

Introduction of training centre x

Abstract xi

Chapter 1: Introduction 1 - 5

Chapter 2: Literature Review 6 - 47

Chapter 3: Patients and Methods 48 - 51

Chapter 4: Results 52 - 74

Chapter 5: Discussion 75 - 80

Limitations/constraints 81

Recommendations 82

References 83 - 89

Questionnaire Annex 1

Ethical clearance Annex 2

Approval certificate Annex 3

Consent form Annex 4

7

LIST OF TABLES

Table 1: Age distribution of atopic dermatitis patients.

Table 2: Sex distribution of patients.

Table 3: Educational level of patients.

Table 4: Age of onset of Atopic Dermatitis

Table 5: Shows duration of disease condition

Table 6: Frequency of family history of atopy

Table 7: General physical condition on presentation

Table 8: Distribution pattern of the rash of AD

Table 9: Relationship of age to the distribution pattern of the rash of atopic dermatitis

Table 10: The frequency distribution of morphology of the rash of atopic dermatitis.

Table 11: The frequency distribution of the likely provoking factors.

Table 12: The frequency distribution of likely exacerbating factors.

Table 13: Exacerbation of AD in relation to season

Table 14: Presence of Home pets or poultry among the patients with AD

Table 15: Health seeking pattern of patients on first appearance of the rash of AD

Table 16: Nature of medication used on first appearance of AD

Table 17: Outcome of treatment in patients that had medications

Table 18: Relationship of monthly earning of patients to health seeking pattern

Table 19: Patients’ responses to the likely cause of AD

8

LIST OF FIGURES

Figure 1: The types of family the patients belonged to.

Figure 2: Frequency of occupation of patients or their parents in the case of children.

Figure 3: Frequency of monthly income of patients or their parents in the case of children.

9

LIST OF PICTURES

Picture 1: Typical facial involvement in a 3 months old infant with characteristic erythema

and scaling of AD.

Picture 2: Miss N B, a 26 year old applicant, showing typical flexural involvement of the elbow

in AD.

Picture 3: A R, a 6 year old female patient, showing extensive flexural involvement of the

knees in AD

Picture 4: D G an 11 month old male patient, showing extensor involvement of AD.

Picture 5: HG, a 4 year old male patient, showing chronic AD.

Picture 6: B M, an 8 year old male, with palmo-plantar fissuring in AD.

10

INTRODUCTION TO 44 NIGERIAN ARMY REFERENCE HOSPITAL KADUNA

The 44 Nigerian Army Reference Hospital, Kaduna (44 NARHK) is the premier military

hospital in Nigeria established in 1944 for the purpose of rehabilitating wounded military

personnel during the Second World War. Today, the hospital however has its gates opened to

both military and civilian patients. It is a 200-bed hospital located on Sokoto road in Kaduna

town the capital city of Kaduna state North Central Nigeria. In the year 2005, the hospital

attended to a total of 25,000 patients out of which 15,000 were attended to in the General Out

Patient Department. The number is expected to rise with the transfer of Ahmadu Bello

University Teaching Hospital, Kaduna to its permanent site at Shika, Zaria.

The hospital offers internship training and the fellowship programme of the National

Postgraduate Medical College and West African College of Physicians in Family Medicine.

The hospital has in its service 15 Consultants of various specializations, 5 resident Doctors in

Family Medicine and 15 interns in addition to other cadre of medical, paramedical and nursing

staff. There are facilities for both outpatient and inpatient care. These include laboratory and

radiological services, physiotherapy, and a National Tuberculosis and Leprosy control

programme dispensing unit in the hospital. There is also HIV/AIDS care partnership

programme centre involving the Nigeria Ministry of Defence and United States Department of

Defence (MOD-DOD). The hospital runs effective preventive health care services such as

immunisation, nutrition, family planning and antenatal clinics.

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ABSTRACT

Background Atopic dermatitis (AD) is a chronic inflammatory pruritic skin disease which

occurs most frequently in children but can occur in adults and follows a relapsing course. It is

often associated with elevated serum IgE levels and a personal or family history of type I

allergies, allergic rhinitis, and asthma.

Objective This study was conducted to determine the prevalence and pattern of presentation of

atopic dermatitis amongst dermatology clinic patients in Kaduna in order to make

recommendations on ways to reduce its morbidity.

Method A descriptive cross sectional study was conducted from July 2005 to December 2005

in the dermatology clinic of Barau Dikko Specialist Hospital, Kaduna, Kaduna state, Nigeria.

Results A total of 200 patients, age range from 3 weeks to 55 years were recruited for this

study. The prevalence of AD in this study was 16.7%, while the prevalence in a study in south-

eastern Nigeria showed 8.5%. AD had its onset before 1 year of age in 167 (82.5%) patients, a

family history of atopy was found in 172 (86.0%) patients. The face was involved in 76 (38.0%)

patients while the flexures were involved in 64 (32.0%). Most of the patients 160 (80.0%) did

not know what causes AD. 72 (36.0%) patients consulted the herbalist when AD appeared for

the first time. The health seeking pattern of the patients when AD appeared for the first time

was not significantly dependent on the monthly earning of our patients (x2 0.795).

Conclusion The prevalence of AD among dermatology clinic patients in Kaduna is relatively

high particularly amongst infants. The pattern of presentation is similar to what is reported in

the western literature. There is ignorance about AD in Kaduna and the people engage in

unorthodox methods of treatment. Health education would go along way in reducing its burden.

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CHAPTER ONE

INTRODUCTION

Atopic dermatitis (AD) is defined as a chronic inflammatory pruritic skin disease which occurs

most frequently in children but can occur in adults and follows a relapsing course1. It is often

associated with elevated serum IgE levels and a personal or family history of type I allergies,

allergic rhinitis, and asthma1.

The disease occurs in all age groups but is commoner in children2. It is slightly commoner in

females than males though the difference has not been consistent3. It also occurs in all races.

The disease is commoner in people living in urban areas and also in dry and cold areas4. Parental

history of atopy or eczema is one of the strongest risk factors of the disease. Atopic dermatitis

and atopy in general seem to be diseases of the advantaged classes5 with the prevalence being

inversely related to the number of siblings6. The true prevalence of AD in the general population

is imprecise as it varies between 10%-30%7. Infrequent remission, unpredictable course, newer

treatment options, lack of uniform diagnostic criteria and nomenclature have been identified as

strong limitations to determining its true prevalence. However studies from different parts of

the world indicate that the prevalence of AD is rising. In Europe, there is a two-three fold

increase in the disease over the past fifty years8 while about 10% of children are affected by

this disease in the United States of America9. A similar picture was reported in Asia where in

Japan there was a two-fold increase in childhood AD cases and a five-fold increase in

adolescents10. The situation is not different in Australia with a current prevalence of 9.7%4. A

rising prevalence was also reported in Africa for example in Nigeria, figures of 3, 3.5, 6.1 and

13

17% were reported4, 11-13. In 2004, Nnoruka in south-eastern Nigeria concluded that AD is

currently on the increase particularly amongst infants and has created a cost burden for families

with a prevalence of 8.5%14. The reason for the rising prevalence is unknown but environmental

factors are thought to be responsible.

The aetiology of AD is unknown but it has a polygenic mode of inheritance and is

multifactorially determined particularly by environmental factors15.

The pathogenesis of atopic dermatitis is elusive, as it is poorly understood despite decades of

research. However, immune dysregulation appears to play an important role15.

Although there are different diagnostic criteria for AD which are discussed in the text, the

Revised Hanifin and Rajka diagnostic criteria adopted by the American Academy of

Dermatologist16 has been used for this study. This is because it provides a simplified system for

defining AD as a syndrome.

Acute, subacute, and chronic eczematous lesions characterize the disease. In the acute phase,

the affected areas present as erythematous papules and vesicles that become excoriated,

exudative, and secondarily infected. In the subacute phase, there are excoriations and

erythematous scaling papules and plaques present. Chronic dermatitis is characterized by

changes secondary to repeated rubbing and scratching resulting in lichenification. Common to

all the stages is intense itching and a course marked by exacerbations and remissions2.

Treatment of Atopic dermatitis is neither complicated nor difficult. At least 80% of patients

have only mild disease as reported by some population based studies10, 17, 18, and their care can

14

remain within the responsibility of their primary care physician. The cornerstones of treatment

are proper bathing techniques, corticosteroid use and health education.

JUSTIFICATION FOR THE STUDY

1. Despite the rising prevalence and the high cost of care, AD has continued to be

misunderstood, misdiagnosed due to poor recognition, and is also ineffectively treated by

medical personnel19. There is the need therefore for proper understanding of AD especially

by family physicians who are frontline doctors.

2. Atopic dermatitis is a distressing condition for both the patients and their families. It has a

considerable impact on health care utilization including direct medical costs; direct family

care cost and indirect costs associated with loss of productivity of parents20-23. It is estimated

that about $364 million is spent yearly on childhood AD in the United States of America

alone2, while in the UK it is about £465 million yearly24.

3. The author is not aware of studies on AD in the northern part of the country where the

weather is dry. The few published studies in Nigeria are from the southern part of the

country where the weather is humid. Most of the studies on the epidemiology and clinical

presentation of AD have been mainly among the Western population. This study therefore

aims to provide useful information from the northern part of Nigeria on AD particularly

because environmental factors such as dry and cold weather are known to be associated

with the disease4.

4. It has been observed from our practice that there is some misconception in this locality

because patients, parents and relatives generally believe that AD cannot be cured by

orthodox medicine but only traditional medicine. The disease also does not have a local

15

name in Hausa, the predominantly spoken language in Kaduna, therefore making

recognition and description difficult for patients or their parents in case of children.

RELEVANCE OF THE STUDY TO FAMILY MEDICINE

a) Atopic dermatitis like other atopic conditions such as vernal conjunctivitis, asthma,

rhinitis, hay fever, commonly presents in General Practice25. This study seeks to provide

adequate knowledge on diagnosis and management of atopic dermatitis, which would

be useful in reducing frequent clinic visits by families, absenteeism from work and the

rate of referrals.

b) Health education is a major component in the management of the disease condition

since it is recurring in nature and has no permanent cure. The family physician as a

provider of continuous care and a health educator is best suited for this role.

c) In examining the health-seeking pattern of families to atopic dermatitis, the study will

further strengthen the management skills of the family physician.

d) Because of the problem of few dermatologists in Nigeria, this study will expose the

author to the management of other commonly encountered skin diseases thereby helping

to reduce the rate of referrals.

e) This study will serve as a reference for further hospital survey on atopic dermatitis in

this environment as the author is not aware of any previous study.

f) The study has also opened an opportunity for further research on atopic dermatitis in

family medicine.

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AIM AND OBJECTIVES

AIM

The aim of this study is to determine the prevalence and pattern of presentation of atopic

dermatitis in Kaduna in order to make recommendations on ways to reduce its morbidity.

OBJECTIVES

1. To determine the prevalence of Atopic Dermatitis in Kaduna.

2. To study the pattern of presentation of the disease.

3. To identify the likely provoking factors of the disease.

4. To study the health seeking pattern of patients or parents (in case of children) on

first appearance of AD.

5. To recommend ways to reduce its morbidity and cost burden.

17

CHAPTER TWO

LITERATURE REVIEW

BACKGROUND, DEFINITION AND TERMINOLOGY

Atopic dermatitis (AD) is a difficult condition to define because it shows variable clinical

features and lacks a diagnostic test. The following definition seems to be in accord with most

consensus groups. Atopic dermatitis (AD) is a chronic inflammatory pruritic skin disease which

occurs most frequently in children but can occur in adults and follows a relapsing course1. It is

often associated with elevated serum IgE levels and a personal or family history of type I

allergies, allergic rhinitis, and asthma1. The rash of the disease is characterised by itchy papules

(occasionally vesicles in infants) which become excoriated and lichenified, and typically have

a flexural distribution. The term atopic dermatitis was first introduced in 1933 by Wise and

Sulzberger in recognition of its close association with respiratory allergy26. The lack of known

cause for atopic dermatitis has led to a wide variety of names for the condition. Although atopic

dermatitis and atopic eczema are the most widely used terminologies for the disease, Besnier’s

prurigo is often used in continental Europe. Previously used terms include Disseminated

Neurodermatitis, Spatexudative Ekzem, and Prurigo diathesique27.

One of the difficulties in defining atopic dermatitis arises from the impreciseness of its

association with atopy and the nature of atopy itself. The term ‘atopy’ (derived from the Greek

word atopia meaning ‘strangeness’ or ‘out of place’) was introduced by Coca and Cook in 1923

as a convenient collective term to describe the unusual association observed in patients with

eczema, allergic conjunctivitis (hay fever) and asthma28 and later in the same year,

18

Immunoglobulin E (IgE) antibodies were detected for the first time in this group of patients.

Atopic dermatitis and disorders that result from anaphylaxis, such as those resulting from insect

stings and food allergies, were found to be associated with IgE antibodies and therefore grouped

with the atopic diseases. Such grouping is not completely acceptable, as 20-40% of individuals

with atopic dermatitis can have a normal total or specific IgE levels. Presence of IgE antibodies

in the blood often appear to be incidental to the condition and are rarely attributable to a specific

allergic reaction27. A gene predisposing to atopy (as defined by hyper-IgE responsiveness) has

been found on chromosome 11q13, and it is possible that it codes for the β-subunit of the high-

affinity IgE type 1 Fc receptor. There is no link between this gene and familial cases of atopic

dermatitis but a weak link may be found with maternal inheritance. Although atopy plays a part

in the majority of cases of atopic dermatitis other factors must also be involved. However the

adjective ‘atopic’ serves to identify and differentiate the condition from wide variety of itchy

skin conditions27.

DIAGNOSTIC CRITERIA

There is no internationally unified and acceptable diagnostic criterion for atopic dermatitis. The

UK Working Party criteria of 1994 and the Consensus guideline on the diagnosis and

management of atopic dermatitis adopted by the American Academy of Dermatology in 2001

are the most widely used. However, both the UK Working Party and American Academy of

Dermatology criteria are modifications of the Hanifin and Rajka29 major and minor diagnostic

criteria.

The Hanifin and Rajka criteria of 1980 allow a uniformity of diagnosis for hospital-based and

experimental studies but are not helpful for population based studies. The major criteria are

found consistently in cases of atopic dermatitis, but the minor criteria are commonly found in

19

control groups. In addition, the criteria have not been validated against a physician’s diagnosis

or tested for repeatability27.

In order to address these issues, Williams and colleagues coordinated a UK working party in

1994 to attempt to refine the criteria of Hanifin and Rajka into a repeatable and validated set of

diagnostic criteria for atopic dermatitis30. The criteria are outlined below.

In order to qualify as a case of atopic dermatitis with the UK diagnostic criteria, the child

must have

An itchy skin condition (or parent report of scratching or rubbing in a child)

Plus three or more of the following

1. Onset below two years (not used if child is under four years)

2. History of skin crease involvement (including cheeks in children under ten years)

3. History of a generally dry skin

4. Personal history of other atopic disease (or history of any atopic disease in a first

degree relative in children under four years)

5. Visible flexural dermatitis (or dermatitis of cheeks/forehead and outer limbs in children

under four years)

These diagnostic guidelines appear to be valid for adults, children, and non-white ethnic groups

suffering from atopic dermatitis and have been validated in a population setting. However they

were primarily developed for epidemiological studies and, of necessity, exclude some

individuals but are not common enough for use when assessing large populations30.

On the other hand, in 2001 a consensus was reached on the diagnosis and management of AD

by the American Academy of Dermatology in which the disease is best viewed as a syndrome.

The syndrome defined the core dermatologic issues related to atopic dermatitis in children and

adolescents which can influence their dermatologic health over a lifetime; and prioritize future

research efforts on epidemiology, pathogenesis, prevention and management of atopic

20

dermatitis. A simplified system for defining atopic dermatitis as a syndrome was therefore

developed16. The criterion used is essentially a revision of the Hanifin–Rajka criteria, the

clinical findings that define the syndrome are outlined below:

A. Essential features (must be present)

1. Pruritus

2. Eczema (acute, subacute, chronic)

a. Typical morphology and age-specific patterns*

b. Chronic or relapsing history

*Patterns include (1) facial, neck, and extensor involvement in infants and children, (2) current or prior

flexural lesions in any age group, (3) sparing of groin and axillary regions.

B. Important features (seen in most cases, adding support to diagnosis)

3. Early age at onset

4. Atopy

a. Personal and/or family history

b. IgE reactivity

5. Xerosis

C. Associated features (these clinical associations help to suggest the diagnosis of AD

but are too non-specific to be used for defining or detecting AD for research or

epidemiologic studies).

1. Atypical vascular responses (e.g., facial pallor, delayed blanch response )

2. Keratosis pilaris/hyperlinear palms/ichthyoses

3. Ocular/periorbital changes

4. Other regional findings (e.g., perioral changes/periauricular lesions

5. Perifollicular accentuation/lichenification/prurigo lesions

Exclusion Criteria: It should be noted that a diagnosis of AD depends on excluding

conditions such as scabies, seborrheic dermatitis, allergic contact dermatitis, ichthyoses,

cutaneous lymphoma, psoriasis, and immune deficiency diseases.

Looking critically at these much applied diagnostic criteria in the African context, African

dermatologists have voiced concern that the much used Hanifin criteria for diagnosis of atopic

dermatitis may need to be modified for use in Africa31. One possible reason for the need of this

21

modification is that the features may be significantly dependent on ethnic and genetic

background.

EPIDEMIOLOGY

Prevalence Estimates

The true prevalence of AD in the general population is imprecise as it varies between 10%-

30%7. Factors contributing to the problem of determining the prevalence of AD are infrequent

remission and unpredictable courses especially in mild cases. Newer treatment options have

changed the natural history of the disease thereby altering the true prevalence10. There is also

the problem of lack of standardization and validation of diagnostic criteria while lack of uniform

universal nomenclature is a strong limiting factor as AD is called Atopic eczema in Britain19.

However studies from different parts of the world indicate that the prevalence of AD is rising.

For example estimates from Europe over the past 50years suggest a two-three fold increase in

the disease8. The prevalence in UK has increased from 12.2% in 1970 to 15% in 199732 while

about 10% of children are affected by this disease in the United States of America9. A similar

picture was seen in Japan with a two-fold increase in childhood AD cases and a five-fold

increase in adolescents as reported by investigators who compared current findings with data

collected 20 years ago10. The situation is not different in Australia with a current prevalence of

9.7%4. A rising prevalence was also reported in Africa and in Nigeria studies carried out by

several workers showed figures of 3, 3.5, 6.1, and 17%4, 11-13. Most recently in October 2004,

Nnoruka in south-eastern Nigeria showed that AD is currently on the increase particularly

amongst infants and has created a cost burden for families with a prevalence of 8.5%14.

22

In view of the lack of understanding of the factors that cause AD, the reason for the rise in AD

prevalence can only be speculated upon. Suggestions have included changes in diet, including

food additives, increased exposure to house dust mite or air pollution, and the greater use of

irritants such as household soaps and detergents8.

Age Distribution

The disease occurs in all age groups but several studies have shown that it is commoner in

infants and children2, 3, 14. Although the symptoms resolve by adolescence in 50 percent of

affected children, the condition can persist into adulthood2.

Sex Differences

Both sexes are affected; in adults more females have the disease; and in children more males,

although a consistent difference between the sexes have not been found3, 8.

Family History

Atopic dermatitis clearly has a hereditary basis. There is an 86% concordance in monozygotic

twins, and 70% to 90% of patients with the condition report a family history of atopy33.

Amongst those who have a first-degree relative with atopy, the rate of atopic dermatitis is much

higher than those with no family history. The most significant risk factor is a parental history

of AD34. Maternal atopy is considered a greater risk factor for atopic disorders in offsprings35,

although recently in 2004 Wadonda-Kabondo and his colleagues36 concluded that associations

between parents’ atopic disease and the risk of atopic dermatitis in offspring vary according to

the type of atopic disease in the parents, but not according to parental sex. They also found that

there is no "parent-of-origin" effect in atopic dermatitis. Parental AD may be a better marker

than parental asthma/hay fever in predisposing to childhood AD.

23

Racial Factors

Studies of ethnic communities have shown that AD is more prevalent amongst Chinese infants

born in San Francisco and Honolulu when compared with the local Caucasian population. Such

a difference has also been shown for black Caribbean children born in London but not for

Indians born in Leicester. Larsen and colleagues observed that children from the Pacific island

of Tokelau documented a higher prevalence of AD amongst a group who had migrated to New

Zealand compared with a similar group of children who had remained in Tokelau8. These

observations suggest a key role for the environment in mediating disease expression.

Socio-Economic Factors

Atopic dermatitis and atopy in general seem to be diseases of the advantaged classes5 with the

prevalence being inversely related to the number of siblings6. Atopic dermatitis has been shown

to be almost twice as common in the higher social classes in the United Kingdom when

compared with the lower social classes. This social gradient in AD was also reflected in the

types of housing conditions; a higher rate of AD was found amongst children in privately owned

properties when compared with those living in council rented properties. One possible

explanation was that families from a higher socioeconomic class tend to have well furnished

apartments and their tendencies to remain indoors with central heating facilities thus exposing

them to the house dust mite.

Environmental Factors

Although environmental factors are important in the aetiology of AD, specific causes remain

to be found. A causative role for foods and aeroallergens is suggested by the findings of some

intervention studies, but there are few studies that have attempted to link exposure to specific

risk factors with AD prevalence in a community setting. Evidence that the onset of AD may be

24

influenced by dietary factors is found in dietary intervention studies. The avoidance of food

allergens in the first twelve months of life by the restriction of cow’s milk, eggs, fish and nuts

in the diet of infants and their breast-feeding mothers, reduces the incidence of AD at one year

of age8. Further observation is needed to confirm the long-term benefits of early intervention

measures. A study by Fergusson and Harwood37 has suggested that a diverse solid food diet

during the first four months of life is a risk factor for the later development of AD. The house

dust mite may be of aetiological importance as clinical improvement of AD can be

demonstrated following intensive eradication of mite allergens in the home, or the removal of

patients to allergen-free environments38. McNally and Williams found a significant relation

between AD prevalence and water hardness amongst primary and secondary school children in

Nottinghamshire. They concluded that hard water in the home may increase the risk of

developing AD39.

Geographical Distribution

Regional variation in prevalence of atopic dermatitis exists within countries. There is evidence

to suggest that AD rates are increased within areas of ‘urbanization’. Leung and Ho observed

that the prevalence of AD was found to be significantly higher in Hong Kong compared with a

nearby rural village in China40. Similarly, AD has been noted to be more common in large cities

in Finland41 and Sweden42 when compared with rural areas. Climate may account for some

regional variation. Agata et al in Japan found the lifetime prevalence amongst children aged

three months to twelve years to be 3.1% in a subtropical region of the country, compared with

19.3% in a temperate zone43. Presumably humidity has a role in

preventing the excessive dryness of the skin seen in AD, although differences in climate may

also lead to differences in housing conditions, such as carpeting and central heating.

25

AETIOPATHOGENESIS

The aetiology of AD is unknown but genetic and environmental factors are very important in

its aetiology and environmental factors are thought to be particularly important15.

The pathogenesis of atopic dermatitis is still poorly understood. Despite decades of intensive

studies and heated debates, the precise relationship between specific allergens (e.g. bacteria,

house dust mites, Pityrosporum) and atopic dermatitis remains elusive but immune

dysregulation appears to play an important role15. In fact, the population of these allergenic

organisms is much higher in tropical countries and during summer months in temperate

climates, yet in these settings, the skin condition actually improves. Mechanistically, atopic

dermatitis may be regarded as an immunologic irritability in which a whole array of non-

specific antigenic and physical stimuli can provoke a flare of the rash. In this regard, the

individual trigger factors do not necessarily impute a direct immune mechanism.

Hereditary background: A family history is obtained in about 70%-90% of all cases33. Those

cases without a family history do not differ materially from the remainder, although they have

a somewhat better prognosis. Clinically normal parents may have affected children, which

exclude a simple dominant inheritance. In other families both parents are affected but the

children are normal, excluding a simple recessive trait. An analysis of familial aggregation of

atopic dermatitis has shown stronger links between siblings than between the mother and the

siblings44. Despite these findings, inconsistent results have been obtained from studies of the

Human Leucocytes Antigen (HLA) complex haplotypes. The authors concluded that

environmental factors, especially during childhood, explain recent increases in the frequency

of atopic dermatitis44.

26

Immunological abnormalities: Increasing knowledge of cell biology and of cytokine

mediators has increased the complexity of the abnormalities observed without revealing the

nature of the basic defects giving rise to the disorder. The main immunological abnormalities

of clinical relevance are aberrations of the genotypes which include an increased allergen-

specific IgE antibody response to common antigens, hyperreleasable basophils and mast cells,

eosinophilia, antigen-driven TH1/TH2 biphasic reversal, high-affinity IgE receptors of

Langerhans cells, mast cells, eosinophils, and TH2 cells15, 27. However, these abnormalities

detected tend to be inconsistent and not apparent in all patients. Differences in laboratory

techniques, especially in the optimum concentrations of test reagents, also lead to conflict of

opinion. The presence or absence of particular defects and their magnitude is not consistently

related to the severity of the disorder27.

The immunological abnormalities were extensively reviewed by Leung15 as enumerated below.

Increased allergen-specific IgE antibody response to common antigens

Atopic individuals are best recognized by their propensity to produce large amounts of specific

IgE antibodies to common substances (i.e. dust mites, pollens, molds, and foods) and drugs.

Skin and/or RAST (radio-allergosorbent) testing can detect these antibodies. Approximately

85% of patients with AD have some positive skin and/or RAST results for inhalant and food

allergens. However, a direct relationship between the positive skin test reactivity to implicated

allergens and the course of AD has been difficult to establish consistently. In fact, most (but not

all), positive skin tests, especially for foods, must be regarded as false positives. Positive skin

and/or RAST tests, however, remain reliable indicators of atopy; if atopy cannot be confirmed

from the history, it would be helpful to perform skin tests or to obtain an IgE level. Thus neither

skin and/or RAST testing nor IgE levels need to be part of a routine AD work-up. The complex

genetics of elevated serum IgE levels gives the determination value only when it is significantly

elevated. It has been reported to be elevated in 43% to 82% of patients with AD. The highest

27

levels are noted when AD coexists with respiratory atopic disease and when the level does not

fluctuate in close association with clinical flares and remissions.

Hyperreleasible basophils and mast cells

Dermal mast cells (of the tryptase-chymase type) are found to be closely associated with blood

vessels and nerves. Mast cells in different anatomic sites, and even in a single site, can differ

substantially in mediator content, in sensitivity to agents that induce activation and mediator

release, and in responses to pharmacologic agents. The hyperreleasability of basophils and mast

cells can be elicited by both immunologic (ie, IgE, substance P) secretagogues, and

nonimmunologic (ie, opiates, aspirin, NSAIDs) secretagogues. The release of vasoactive

mediators, chemotactic factors, and cytokines initiate the “allergic cascade.” The case for a

mast-cell role in the pathogenesis of AD was essentially rooted on its association with allergic

rhinitis and asthma and on the assumption that histamine (a predominant pro-inflammatory

mediator released with mast-cell activation) was the sole pruritogenic agent. It was noted that

mast cells do not appear to be required in some animal models of allergic disease. In contrast,

helper TH2 lymphocytes (with their cytokinal profile of IL-4, IL-13, and IL-5) are essential to

elicit the late-phase response. Although earlier studies detected elevated skin histamine in AD

skin, recent, more sensitive and specific radioenzyme assay found elevated histamine content

in only 3 of 22 patients with AD. Elevated plasma histamine levels have also been noted in

some patients with AD, but its significance is obscure, because elevated histamine levels have

been noted in a variety of inflammatory skin diseases. The role of histamine in AD was

convincingly refuted (on the basis of the negligible relief of itch) and the beneficial effect on

the eczema of AD from antihistamines. The elevated IgE responses and eosinophilia observed

in some patients with AD reflects the increased expression of TH2 cytokines (ie, increased IL-

4, IL-5, and IL-13 with a concomitant decrease in IFN-γ).

Eosinophilia

28

Eosinophilia occurs in a variety of disorders, but the most common cause in industrialized

nations is atopic disease. Diseases involving eosinophilia are the result of stem-cell activation

by IL-5, which in allergic diseases is predominantly a product of TH2 cells. Tissue eosinophilia

is a hallmark of atopic diseases, and they are believed to be a major effector cell in the late-

phase response of patients with repeated exposure to an allergen (e.g. house dust mite). It was

found that eosinophil-derived extracellular major basic protein is extensively deposited in the

skin of patients with AD. Although the role of eosinophils in the pathogenesis of AD is not

completely understood and because major basic protein (an eosinophil product) correlates with

disease activity, they are thought to contribute to tissue injury in AD. Therapeutically, the

beneficial effects of glucocorticoids are associated with reducing eosinophilia and the

production and action of their products. The 5-lipo-oxygenase inhibitors (eg, zileuton) have

been shown to inhibit the generation of the eosinophil chemo-attractant leukotriene B4. Several

studies have evaluated the effect of montelukast, (an antileukotriene medication) on peripheral

blood eosinophils; when it was compared with placebo, the drug significantly decreased

eosinophils by approximately 15%.

TH1/TH2 (biphasic) response.

The clinical significance of T cells can be noted by their capacity to modulate immune

responses by help or suppression or to effect cytotoxic immune responses. This response is

dependent on the profile of cytokines they produce. T cells that produce predominantly IL-2,

IFN-γ, and TNF-β are referred to as TH1 cells; T cells that produce predominantly IL-4, IL-5,

and IL-13 are referred to as TH2 cells. The consequence of these reciprocal cytokine patterns is

the generation of cell-mediated immune responses (e.g., delayed-type hypersensitivity) by TH1

cells and of humoral allergic immune responses by TH2 cells. The immunologic hallmark of AD

is a TH1/TH2 dysbalance. The eczematous lesions of AD have more similarities to delayed

hypersensitivity (e.g., allergic contact dermatitis) than to the urticarial lesions of immediate

29

hypersensitivity. In the early stages of both involved and uninvolved skin of patients with AD,

allergen-induced activation of TH2 cells predominate over (IL-12 driven) TH1 cells. The TH2-

cytokine profile of IL-4 and IL-5 favours IgE production and eosinophilia, respectively, which

are essential to the atopic diathesis. The decreased TH1 population noted in the early stages of

AD results in an increased susceptibility to viral (e.g., warts, molluscum, and herpes) and

dermatophytic (e.g., tinea pedis, tinea cruris) infections, plus the relative anergy for the

elicitation of allergic contact dermatitis. However, in the late and chronic phases of AD, the

situation reverses and IFN-γ production by TH1 cells predominate. This observed biphasic

response explains many of the previously considered controversial issues (i.e., their ability to

become sensitized to topical allergens) regarding AD.

High-affinity IgE receptors (FcRI)

The best studied pathway of mast cell and basophil activation is transduced through FcRI that

is expressed on the surface of those cells. When adjacent FcRIs are bridged, the cells are rapidly

activated for the release of stored and newly generated mediators. The cells can be sensitized

simultaneously with IgE antibodies of much different specificity and therefore can react to

stimulation by many different antigens. IgE- and antigen-dependent activation is the basis for

the immunologically specific expression of mast and basophil function in IgE-dependent

immune responses and allergic disorders (e.g. allergic rhinitis, extrinsic asthma). Epidermal

Langerhans’ cells have also been recognized to express variable amounts of FcRI (and other

immunoglobulin receptors), and the strongest expression is characteristic of the involved skin

of AD. The receptor is believed to take part in the pathophysiologic features of this disease by

acting as a link between aeroallergens and Ag-specific T cells in an IgE-mediated, delayed-type

hypersensitivity reaction. The expressions of the FcRI receptor on eosinophils and T cells

infiltrating lesions of AD have recently been reported. Chronic inflammation may be sustained

through local antigen processing and presentation to allergen-specific eosinophils and T cells.

30

The clinical significance of the FcRI receptors of Langerhans’ cells in AD is supported by the

reduction of the number of dermal Langerhans’ cells and mast cells with significant clinical

improvement after treatment with high-dose ultraviolet-1 light therapy.

Pharmacological and vascular abnormalities15: The small blood vessels in atopic dermatitis

show a tendency to vasoconstriction. This is manifest as pallor of the skin; low temperature;

pronounced vasoconstriction on exposure to cold; white dermographism; abnormal reactions to

histamine in affected skin; white reaction to nicotinic acid esters; delayed blanch with

acetylcholine. None of these findings is pathognomonic. The delayed blanch phenomenon with

acetylcholine and related drugs is characteristic for atopic dermatitis, and occurs less regularly

with other atopic disorders. Whether these pharmacologic changes in atopic dermatitis are

secondary to cutaneous inflammation or the deranged pharmacology and the immune

abnormalities are both secondary to a common defect is not known.

Itching: Intense pruritus and cutaneous reactivity are the cardinal features of AD. In 1891, the

French dermatologist Jacquet first suggested that it was not the rash that itches but that the itch

was the initial event15. Areas of atopic dermatitis itch more readily and more persistently with

stimuli which normally elicit itching, for example histamine or proteolytic enzymes, and may

respond with the sensation of itch to stimuli which are normally only felt as touch. This accounts

for much of the intolerance of atopic dermatitis patients to wool. Scratching and lichenification

can ensure, to produce a vicious cycle. In atopic dermatitis it is often impossible to determine

which lesions are primary and which follow itching and scratching. Lichenification is not

peculiar to the atopic individual, and not all patients with atopic dermatitis are capable of

producing this epidermal thickening. It appears unlikely that histamine is a key factor in this

inherent itchiness, and its basis is unknown45.

Sweating: Many patients are aware that sweating aggravates their condition. Disturbances of

sweating due to poral occlusion may occur, and ingested allergens or allergens derived from

31

sweat may be excreted in the sweat. There is greater response of the sweat glands in atopic

dermatitis to acetylcholine27.

Psychological and central nervous system factors27: These play a variable role. The evidence

for an atopic personality (outwardly calm, seething with suppress anxieties and frustration,

insecurity, aggression, egoism, above-average intelligence) is conflicting. Persistence of

disease throughout infancy cause personality changes which further aggravate the disease. The

habit of scratching may become an automatic reflex, so that an infant will start to scratch as

soon as his hands come in contact not only with his skin but even other people’s skin.

Epidermal changes27: Minor degrees of ichthyoses and keratosis pilaris are common in atopic

dermatitis as judged clinically, although there must often be considerable doubt whether dry

skin and its associated barrier defect, is due to a genetically determined tendency to icthyosis

or is secondary to atopic dermatitis. Keratosis pilaris and increased palmar markings

accompany icthyosis, but are not specifically associated with atopic dermatitis. There is

reduction of total ceramides in non-lesional atopic dermatitis skin, and abnormalities of

ceramide synthesis have been reported. The dryness is associated with lowered resistance to

irritant substances. Transdermal water loss is increased. In a small proportion of cases the

epidermal changes are more severe, irreversible, and dominate the clinical picture.

Bacteriology: The skin of patients with atopic dermatitis tends to carry more staphylococci,

even without clinical evidence of infection. S aureus is found in more than 90% of AD skin

lesions. In contrast, only 5% of normal subjects harbour this organism, and its localization is

mainly in the nose and intertriginous areas15. The organisms may act as immune cell activators,

particularly for IgE synthesis, but it remains uncertain to what extent they contribute to the

disease or are secondary to it. There may also be allergic reactions to Pityrosporum ovale or to

other allergens in human dander. Clinical infection is very common in atopic dermatitis, and in

some such cases impaired neutrophil chemotaxis has been demonstrated27.

32

The role of food allergy: Food allergies deserve special mention in regard to atopic dermatitis.

The medical literature on the role of food allergies is extensive and controversial.

For the majority of atopic dermatitis patients, positive radio-allergosorbent or prick tests to a

variety of foodstuffs can be documented. However, very few of these reactions appear to be

relevant. It is worthy to mention that Sampson and his colleagues46 concluded that laboratory

and clinical investigations over the past two decades have demonstrated that food allergy plays

a pathogenic role in a subset of patients, primarily infants and children, with atopic dermatitis.

Approximately 40% of infants and young children with moderate to severe AD have food

allergy, but identifying this subset of patients and isolating the relevant food allergens requires

a high index of suspicion, the use of appropriate laboratory tests, and, in some cases, physician-

supervised oral food challenges. Removal of the causal food protein(s) leads to clinical

improvement but requires a great deal of education because most of the common causal foods

(egg, milk, wheat, soy, peanut, and so forth) are ubiquitous in the food supply, and food

elimination diets risk causing nutritional deficits. Fortunately, most food allergies resolve in

early childhood, and food allergy is not a common cause for AD in older children and adults.

The hygiene theory47: The hygiene hypothesis states that insufficient exposure to certain

infectious agents during childhood increases the risk of developing asthma and atopic diseases.

Improvements in hygiene levels may be partly responsible for this decline in exposure. Sheriff

and colleagues have established an independent association between infant hygiene score and

both wheeze and atopic eczema reported during the period 30–42 months, which supports the

hygiene hypothesis. Their findings were not significantly attenuated or mediated by increased

use of chemical household products, nor were they affected by other social, maternal, or

environmental factors known to be important in the aetiology of atopic disorders. However, this

is not to say that some as yet unmeasured factor for which hygiene may be a proxy is responsible

for the observed associations. The importance of hygiene in public health should not be

33

dismissed; however, the creation of a sterile environment through excessive cleanliness may

potentially be harmful to the immune system.

Williams and his colleagues48 through the first systematic review of the epidemiological

literature focusing exclusively on AD and the 'hygiene hypothesis' found evidence to support

an inverse relationship between AD and endotoxins, early day care and animal exposure. Two

well-designed cohort studies have found a positive association between infections in early life

and AD, and measles vaccination and AD. Antibiotic use was consistently associated with an

increase in AD risk even into the antenatal period, although a few studies did not reach

conventional statistical significance. A few small randomized controlled trials have suggested

that probiotics can reduce AD severity and that probiotics may also be able to prevent AD to

some degree.

Triggers49: There are many triggering or provocative factors in this disorder that patients

may need to avoid. Physical stimuli include hot or cold ambient temperature, changes in

temperature, low humidity, friction, rubbing or mechanical stimulation, scratching, sweating,

and exercise. Intolerance of wool and other scratchy fabrics is characteristic of atopic

dermatitis, and these materials should be avoided. Below is a list of triggers.

Xerosis (dryness of the skin)

All irritants

Lipid solvents (soaps or detergents)

Disinfectants (e.g. chlorine in swimming pools)

Occupational irritants

Contact and airborne allergens

Dust mites

Pollens

Molds

34

Human dander

Microbial agents

Viral infections (especially upper respiratory infections)

Staphylococcus aureus

Pityrosporum yeast

Candida

Dermatophytes

Others

Foods (contact irritants>vasodilators>allergens)

Psychogenic factors

Climate

Hormones

PATHOLOGY

The histological changes are not specific, and are those of a subacute or chronic eczema. In

infancy, early lesions show acanthosis and sometimes spongiosis, oedema of the dermis, and

infiltration with lymphocytes, histiocytes, plasma cells and eosinophils, sometimes in large

numbers. In later age groups the histology is that of lichenification, sometimes with more

eosinophils in the dermis than are found in lichen simplex, and with an increase in the number

of Langerhans’ cells. Eosinophilia in tissues as well as in peripheral blood is found in many

cases of atopic dermatitis, but is of no help in determining the role of allergy in producing the

symptoms27.

35

CLINICAL FEATURES

Atopic dermatitis is an itchy, chronic and fluctuating disease. The age of onset is between two

and six months in the majority of cases, but may start at any age, even before the age of two

months in some cases27. The clinical features include:

1. Itching;

2. Macular erythema, papules or papulovesicles;

3. Eczematous areas with crusting;

4. Lichenification and excoriation;

5. Dryness of the skin;

6. Secondary infection.

The evolution stages of atopic dermatitis include acute, subacute, and chronic eczematous

lesions. In the acute phase, the affected areas present as erythematous papules and vesicles that

becomes excoriated, exudative, and secondarily infected. In the subacute phase, there are

excoriations and erythematous scaling papules and plaques present. Chronic dermatitis is

characterized by changes secondary to repeated rubbing and scratching resulting in

lichenification. Common to all the stages is intense itching and a course marked by

exacerbations and remissions2.

The distribution of the eruption varies with age which can present with any of the evolution

stages. The distribution by age is described below.

Infantile phase: The lesions most frequently start on the face, but may occur anywhere on the

skin surface. Often the napkin area is relatively spared. When the child begins to crawl, the

exposed surfaces, especially the extensor aspect of the knees, are most involved. The lesions

consist of erythema and discrete or confluent oedematous papules. The papules are intensely

36

itchy, and may become exudative and crusted as a result of rubbing. Secondary infection and

lymphadenopathy are common. The disease runs a chronic, fluctuating course, varying with

factors as teething, respiratory infections; emotional upset and climatic changes27.

Childhood phase: From 18-24 months onwards the site most characteristically involved are

the elbow and knee flexures, side of the neck, wrists and ankles. The sides of the neck may

show a striking reticulate pigmentation. The anatomical basis for this distribution is unknown.

Sometimes only one side is involved. The erythematous and oedematous papules tend to be

replaced by lichenification. Some patients with atopic dermatitis are apparently unable to

lichenify, even after prolonged rubbing, and they may be difficult to treat. Patients with an

extensor distribution of eczema in later childhood are uncommon and may take longer to remit.

This distribution is said to be commoner in Asian or black children but frequently they show

the typical distribution50. As much as the typical mixture of papules and lichenification, the

eczematous lesions with vesiculation may occur, often with exudative lesions, and sometimes

with nail changes are common. Acute generalised or localised vesiculation should always

suggest the possibility of secondary bacterial or viral infection27.

Adult phase: The picture is similar to that in later childhood, with lichenification, especially of

the flexures and hands. Localized patches of atopic dermatitis can occur on the nipples,

especially in adolescent and young women. Nipple dermatitis has been reported to occur in 3%

to 20% of patients with atopic dermatitis. When it occurs unilaterally, the pruritus and

intermittent course in an atopic patient should lessen the suspicion of Paget’s disease43.

Involvement of the vermilion of the lips (cheilitis) and the adjacent skin is commonly an atopic

manifestation. Follicular lichenified papules are a frequent feature in black people and the

Japanese. A distribution on the face, upper arms and back may correlate with areas of maximal

thermal sweating or pityrosporum orbiculare sensitivity27.

37

Other clinical presentations of atopic dermatitis as extensively reviewed by Beltrani49 are

enumerated below.

Palmar/plantar dermatitis

Palmar/plantar dermatitis occurs in as many as 70% of children with atopic dermatitis. The

incidence of atopy in patients with chronic hand eczema, including dyshidrosis (or pompholyx)

is about 47% to 64%. More importantly, atopic hand dermatitis is the major cause of work-

related disability caused by skin disease; in fact, a history of childhood AD is most indicative

of a risk factor for work-related skin lesions. The “twitchy” skin of atopic patients is most

susceptible to all irritants (i.e. cleansers, solvents, juices from foods), especially “wet work”

exposure. The easy accessibility for rubbing of the palms results in thickened, dry, leathery

palmar skin. The lack of exaggerated dermatoglyphics differentiates these findings from

lichenification. The thickened skin may appear slightly erythematous and scaly, and the

fingertips can appear fissured and have the feel of a ping pong ball. When the erythema is the

result of papulovesiculation, it can be labelled dyshidrosis. The dorsum of the hand may or may

not be similarly involved, but if eczema is present, allergic or irritant contact dermatitis must

be considered. “Sweaty sock dermatitis” or juvenile plantar dermatosis, which frequently is

misdiagnosed and treated as athlete’s foot, occurs in up to 57% of atopic patients. Sparing of

the interdigital spaces between the toes should negate consideration of a possible dermatophytic

infection.

Xerosis

There is no exact definition of xerosis, but it is recognized as finely scaling, clinically non-

inflamed skin involving large areas of the body. It is considered to be the most common skin

finding of atopic individuals, and it persists throughout their life independent of the activity of

other atopic symptoms, but a history of seasonal variations is found in about 75% of patients

38

with AD. Awareness of the significance of xerosis in atopic patients emphasizes the importance

of lubrication and hydration in the management of the condition.

Keratosis Pilaris

Keratosis pilaris occurs in up to 55% of atopic patients either with or without AD and in 15%

of non atopic patients. It may occur as an isolated abnormality or may be seen in several

inflammatory dermatoses. It is most often noted on the extensor aspects of the upper arms,

thighs, and buttocks but can be generalized, including the face. Keratosis pilaris is regarded as

a defect of keratinisation of the (xerotic) hair follicles, in which the follicular openings are filled

with homy plugs, making the skin feel rough (like “chicken skin”) and dry. It appears in

childhood, reaches its peak incidence in adolescence, and becomes less apparent during

adulthood4. Keratosis pilaris is essentially asymptomatic but may be cosmetically unacceptable

(especially to teenagers). Perifollicular accentuation has been described, especially in

pigmented individuals.

Anterior neck fold

Anterior neck fold is described in the literature as a prominent visible, horizontal fold,

running across the middle of the anterior neck of some atopic patients. Like the Denny-Morgan

line, it has little clinical significance.

Eye findings

The associated eye findings are described as allergic shiners; symmetric, asymptomatic, blue-

gray darkening of the orbital skin occurs in about 60% of atopic patients (with or without AD)

and in 38% of non atopic patients. Although there is a tendency for orbital darkening to fade

with age, it is often seen in other atopic family members. It seems to be more apparent in atopic

patients who also have chronic nasal congestion. Except for its being cosmetically unacceptable

for some, it does not require treatment.

Dennie-Morgan lines

39

Dennie-Morgan lines are symmetric, prominent folds below the margin of the lower eyelids

(similar to that seen in patients with Down syndrome). Originally it was described as occurring

in 100% of atopic patients and subsequently noted in 60% to 80% of atopic patients, with a

possible ethnic variation. Morgan noted that it was present usually at birth, or shortly thereafter,

and that it persisted for life.

Periorbital milia

Periorbital milia are tiny, 1- to 2-mm dome-shaped white or yellowish papulonodules, occurring

individually or in clusters periorbitally. These intraepidermal inclusion cysts form when the

disrupted, dry epidermis of atopic patients obstructs the duct of the sebaceous glands. The white

milium body is composed of lamellated keratin. It can also occur as a result of chronic

corticosteroid-induced atrophy. Incision and drainage with a small needle effectively removes

this cosmetic nuisance.

Anterior capsular cataracts

Anterior capsular cataracts tend to develop during adolescence or early adult life, with the peak

incidence between 15 and 25 years of age. The incidence of these cataracts is from 3% to 10%

of patients with AD. The anterior location and shield-shaped cataracts are typical for patients

with AD. They almost always occur bilaterally.

Keratoconus

Keratoconus is a conical deformity of the cornea, occurs ten times more frequently in patients

with AD than in control subjects, and is thought to result from the increased, constant rubbing

of the eyes in patients with eczema and allergic rhinitis.

Atopic keratoconjunctivitis

Atopic keratoconjunctivitis is an inflammatory process that can involve any ocular surface and

is almost always associated with AD. It is always bilateral, can be very pruritic, with burning

and tearing and a heavy mucoid discharge. It is frequently associated with eyelid dermatitis.

40

The incidence of ocular involvement in AD, reported in the ophthalmologic literature, is from

25% to 42%. This statistic should alert the allergist and dermatologist to carefully evaluate the

eyes of all patients with AD49.

Vascular abnormalities

The vascular abnormalities seen in atopy include pallor of the skin, white dermatographism,

pronounced vasoconstriction on exposure to cold, low finger temperature, paradoxic skin

reactions to histamine, nicotinic acid esters, and acetylcholine.

Facial pallor

Atopic persons have been noted to have a peculiar pallor that gives their skin a grayish hue; it

is noted in patients of any race and is believed to be due to the atopic patient’s vascular tone.

White dermatographism

Lightly stroking the skin of atopic patients’ results in white dermatographism (a white line,

without whealing, which rapidly replaces the initial erythematous reaction). Its incidence does

not exceed 80% of atopic patients; however, it has been noted to be age dependent and to

increase from 11% in patients one to two months of age to 85% in patients older than seven

months. There was no correlation between the demonstrability of white dermatographism in

early infancy and the prognosis of AD.

Thermal sweating abnormalities

Heat stroke and exercise-induced cholinergic urticaria is thought to occur almost exclusively in

atopic patients. Many patients are aware that sweating aggravates their AD.

Complications of atopic dermatitis

Impact on quality of life: The psychosocial aspect. Atopic dermatitis has a profound effect

on many aspects of patients’ lives and the lives of their families. In children, one of the most

disturbing impacts of the disease is on the sleep pattern. This can lead to behavioural difficulties

41

in the most severely affected children. The patient’s dermatitis can also interfere with the

functioning of the family51.

Retarded growth27: Retarded growth can be associated with atopic dermatitis. It used to be

seen in severe cases before the advent of corticosteroid therapy, and can therefore be attributed

to the disease. However, suspicion must also clearly rest on both oral and topical steroid

therapy, which can cause growth stunting in any child on long-term therapy. No data are

available with regard to what amount of steroid and what duration of therapy constitutes a

significant risk.

Sudden death: sudden death was once reported to occur, in an infant with severe atopic

dermatitis soon after admission to hospital. However, it is now extremely uncommon27.

NATURAL HISTORY AND PROGNOSIS

There is a correlation between the age of onset of AD and its severity. The earlier the age of

onset, the more severe the course52. Approximately 60% of patients experience the development

of signs of AD before their first birthday, and another 30% experience the development by age

five years49. Though the natural course of AD is highly variable, many cases resolve before age

two years, and in the remaining patients improvement at puberty is common. Ominous signs of

a more persistent course are (1) early flexural involvement, (2) early extensive involvement, (3)

“egg sensitive” patients, and (4) accompaniment by respiratory symptoms. It is rare to see AD

after mid-life (Fifty years of age)49. However, despite the resolution of the eczematous

component in atopic patients, many of the non-essential (or minor) findings (i.e. xerosis,

keratosis pilaris) persist for the rest of the patients’ life. Wuthrich53 reported his epidemiologic

survey of more than 200 patients with AD. In the study, only 11.3% of the patients were

considered cured, and a persistence rate of 63.1% was noted. Twenty-six percent of patients

42

experienced healing during puberty, but in 20% of patients the eczema reappeared. He noted

that up to 60% of the patients with AD also manifested respiratory allergies by age 23 years.

He also noted that there was an inverse relationship between the AD and those patients with

asthma (i.e. when asthma worsened, the AD tended to improve, and vice versa). Hay fever, by

contrast, appeared to be independent of the skin condition. However in a separate observation

by Jonathan and Paller54, they concluded that the cutaneous manifestations of atopy often

represent the beginning of the atopic march. On the basis of several longitudinal studies,

approximately half of AD patients will develop asthma, particularly with severe AD, and two

thirds will develop allergic rhinitis. Epicutaneous sensitization has been thought to be

responsible, with subsequent migration of sensitized T cells into the nose and airways, causing

upper and lower airway disease. Animal models and human observation concur with this theory.

Preliminary prevention studies with oral antihistamines provide evidence that early intervention

might slow the atopic march.

Predicting the course of AD is generally quite difficult. Seasonal variations are reported by

many atopic patients, usually improving in the summer (ultraviolet light exposure and more

relative humidity), worsening in the winter. Exacerbations of eczema may occur in any patient,

usually after an encounter with any one of the “triggers” of itch. Remissions are noted by many

patients, some of which may last for more than ten years.

DIAGNOSIS

The diagnosis of atopic dermatitis is usually based on clinical criteria. The diagnostic criteria

adopted by the American Academy of Dermatology after a consensus conference in January

2001, appear to be valid for adults, children and infants of whites and non-white groups.

43

DIFFERENTIAL DIAGNOSIS

Because the skin lesions in atopic dermatitis can take many forms (papules, vesicles, plaques,

nodules and excoriations), the differential diagnosis of atopic dermatitis is extensive.

Conditions that need to be considered in patients with pruritus include seborrheic dermatitis,

psoriasis and neurodermatitis. Systemic illnesses such as malignancy, thyroid disorders and

hepatic or renal failure can also cause pruritus and excoriations. In adults with new-onset

pruritus, a thorough history and a complete physical examination are necessary to exclude

systemic disease. Features that distinguish these and other conditions from atopic dermatitis are

outlined below55.

Seborrheic dermatitis of infancy

Red, shiny, relatively well-demarcated eruptions typically involving the diaper area are present

in infants four months of age or younger. The lower abdomen and armpits may also be involved,

and scalp scaling (cradle cap) may be present. The infant appears comfortable. The condition

clears within a few months.

Adult-type seborrheic dermatitis

Poorly defined erythema due to overgrowth of or sensitivity to malassezia yeasts is present in

seborrheic areas (i.e., sides of nose, eyebrows, external ear canal, scalp, front of chest, axillae,

and groin creases).

Discoid (nummular) eczema

Circular “cracked” areas of erythema 1 to 5 cm in diameter are present initially on the limbs,

often with secondary infection in children; discoid eczema is most commonly associated with

atopic dermatitis and is often confused with tinea (ringworm). In adults, it may be associated

with excessive skin dryness and secondary infection with Staphylococcus aureus.

Irritant contact dermatitis

44

Cumulative damage to the skin barrier from irritants such as soaps and detergents is present.

The clinical appearance can be identical to that of atopic dermatitis, but location at sites of

maximal exposure (e.g., fingers) may be helpful in making the diagnosis. Some degree of

irritant contact dermatitis is common in persons with atopic dermatitis (e.g., in babies, around

the mouth, owing to saliva and wet food, and in the diaper area, owing to urine).

Allergic contact dermatitis

A hypersensitivity reaction exists after sensitization to specific substances (e.g., the nickel in

jewellery, the rubber in gloves, or the glues in some shoes). Localization may suggest this

diagnosis, but patch tests are needed to definitively establish it. This diagnosis may coexist with

atopic dermatitis.

Frictional lichenoid dermatitis

Shiny papules occur at elbows, knees, and backs of hands, probably related to friction. The

diagnosis may be common, and may be more so in patients with atopic dermatitis.

Neuro-dermatitis

There is usually a single patch in an area accessible to scratching; absence of family history.

Systemic

Findings on complete history and physical examination vary by disease.

Psoriasis

Localized patches on extensor surfaces, scalp, buttocks; pitted nails usually, a single patch in

an area accessible to itching; absence of family history.

Scabies

Infestation may produce non-specific eczematous changes on the entire body. Burrows and

pustules on palms, soles, genitalia, and between fingers help to establish diagnosis.

Onchocerciasis

45

The chronic phase may be accompanied by widespread itching and lichenification of the skin

similar to those seen in cases of chronic atopic dermatitis.

Insect bites

Secondary eczematous changes may develop in the area of the bites, especially on the limbs,

and may be confused with atopic dermatitis.

Immuno-deficiency states (e.g. HIV)

There is usually a history of recurrent infections and other constitutional symptoms.

INVESTIGATIONS

The diagnosis of atopic dermatitis is rarely aided by investigations27. So far no data have shown

any benefit from routine estimation of the total serum IgE concentration or identification of

specific IgE antibodies to common allergens such as house dust mite, pollens, or food mix using

skin prick testing or the radioallergosorbant test (RAST). These tests are unable to predict the

outcome of avoiding appropriate antigens. In addition, 15% of apparently healthy people have

raised IgE titres while 20% of patients with clear clinical evidence of atopic dermatitis do not

have raised IgE titres or a positive radioallergosorbant test. In older patients in whom there is

46

diagnostic difficulty, measuring total serum IgE may sometimes be useful. Deterioration in

patients with previously stable or mild atopic dermatitis may be due to secondary bacterial or

viral infection or to development of contact dermatitis25.

Bacteriological swabs are not routinely indicated but may be necessary if patients do not

respond to treatment in order to identify antibiotic resistant strains of staphylococcus aureus

and detect additional streptococcal infection. If herpes simplex infection is suspected, swabs

should be sent for virological screening and a smear sent for electron microscopy if this service

is available.

Patch testing should be considered not only in patients whose conditions have deteriorated but

also in those who seem unresponsive to treatment as sensitisation to topical treatments,

including steroids, have been reported in atopic dermatitis25.

TREATMENT

Atopic dermatitis is a condition which is variable in severity and age of onset. Treatment should

be tailored to an individual’s needs, bearing in mind age, sex, social conditions, site of

involvement and severity27. Treatment of atopic dermatitis requires a comprehensive approach

that includes evaluation of potential triggers and education of the patient and family regarding

proper avoidance measures56.

It is however important to note that treatment of atopic dermatitis is neither complicated nor

difficult. The vast majority of patients have only mild to moderate disease, and thus their care

47

can remain within the responsibility of their primary care physician19. At least 80% of patients

have only mild disease as reported by some population based studies17, 18.

The treatment is broadly divided into first, second and third line measures.

First-line treatment

General advice: One of the most important aspects in the management of atopic dermatitis is

to allow adequate time for explanation and discussion. In order to develop a strategy, patient’s

specific requirements (the term patient refers to the individual or the carers in the case of an

infant or child) should be discussed, and achievable aims agreed. These may include

improvement in a range of factors such as decreasing itch, improving sleep, reducing

absenteeism from work/school, or improving family interactions.

Education about atopic dermatitis by doctors, nurse specialist and self-help groups, is very

helpful in achieving these aims. Patient should be taught current knowledge of the disease, the

types of trigger factors, the treatment options and their likely benefits and risks. Demonstration

of the use of topically applied medications, bandages, or wet wraps, will improve compliance

and disease control.

Reduction and or avoidance of trigger factors: Atopic dermatitis can be aggravated by a

variety of trigger factors. These will vary between patients, and differ at various times in an

individual patient. Soaps and detergents remove natural lipid from the surface of the skin. This

is undesirable in all patients with atopic eczema as they already have dry skin. A dispersible

cream should be used as a soap substitute to cleanse the skin. Extremes of temperature should

be avoided, nails should be kept short, and irritant clothing such as woollens should not be worn

next to the skin. Cotton clothing is more comfortable and recommended1.

48

Atopic dermatitis is not a contraindication to routine childhood immunizations27. Although egg

protein is present in some vaccines the amount is so small that it should not be a problem in

practice, unless the child has documented severe systemic reactions to egg protein. If in

doubt, the vaccination should be supervised in an environment with resuscitative equipment

available.

Parents should be advised about the risk of herpes simplex infection in a child with atopic

dermatitis because the underlying disorder suggests dysregulation of the cell mediated

immunity which is also the defence mechanism in viral infections. Parents are also told to avoid

contact of active cold sores with the child’s skin.

Not only can stress aggravate atopic dermatitis, but in a severely affected child is also a source

of stress to the whole family. The doctor’s role in giving simple reassurance and listening to

family problems should not be underestimated. Stress can respond to treatment, and the

dermatitis can be improved by using a variety of cognitive behaviour techniques and group

therapy.

Proper bathing and application of emollients: Bathing is useful for most patients for both

cleansing and hydrating the skin. Patients should be allowed to decide on the most suitable bath

oil and bathing regimen. Emollients provide a surface lipid film which retards evaporative water

loss from the epidermis. They are most effective when applied after bathing as this is when the

water content of the skin is greatest. Emollients should be reapplied to exposed areas such as

the hands and face at regular intervals throughout the day as the lipid film also provides some

protection against external irritants. In general the more oily the preparation, the better the

emollient effect. However, adults, and adolescents in particular, often find the greasiest

preparations too messy for routine use, and some patients prefer to use different emollients for

49

the face and body. The doctor's role is to help patients find an emollient that is effective and

cosmetically acceptable to them in order to ensure regular use. Sufficient quantities of emollient

should be prescribed to allow it to be applied liberally at least twice a day. If emollients are

being applied to the whole body, children will require at least 250 g per week and adults 500 g

per week24.

Topical corticosteroids: Since their introduction approximately 50 years ago, topical

corticosteroids have been the mainstay of treatment for atopic dermatitis, showing efficacy in

both acute and chronic disease. By acting on multiple resident and infiltrating cells, primarily

through suppression of inflammatory genes, they are effective in reducing inflammation and

pruritus57. The use of steroids in the management of AD was extensively reviewed by McHenry

and colleagues25 and concludes that they can be used safely if certain precautions are taken.

Use and abuse of topical steroids has caused considerable confusion and controversy and has

resulted in the undertreatment of many patients with atopic eczema. Lack of adherence to

treatment may often be traced back to patients' or parents' fears of steroids. It is therefore

important to explain the different potencies and the benefits and risks of topical corticosteroids.

The basic principle is to use the least potent preparation required to keep the eczema under

control, and when possible the corticosteroids should be stopped for short periods. To minimise

potential side effects when prescribing topical corticosteroids it is important to consider the age

of the patient, the site to be treated, the extent of the disease, the type of preparation, and the

method of application.

Age- For most children with mild to moderate eczema 1% hydrocortisone ointment is adequate.

It does not cause systemic side effects related to percutaneous absorption unless used

extravagantly on very small babies. In older children moderately potent steroids may be needed

for short periods to gain control of the disease. Preparations in the very potent and potent

categories should be used with caution for limited periods only.

50

Site- Corticosteroid absorption is increased at certain sites such as the face and flexures,

particularly in the presence of eczema. On the face, the principal risk is the development of

permanent telangiectasia, and in general only 1% hydrocortisone should be used here in all age

groups. Long term use of topical steroids in the eyelid area has been associated with the

development of glaucoma. Topical corticosteroids, including 1% hydrocortisone, should be

used with caution at this site, particularly if there is a personal or family history of glaucoma.

Care should be taken, especially in adolescence, to avoid striae atrophicae when using more

potent preparations in other high risk sites such as the breasts, abdomen, upper arms, and thighs.

These can result in permanent disfigurement. On the palms and soles potent preparations may

be used for a longer period as only a small area is being treated and percutaneous absorption is

reduced.

Extent of dermatitis- The potential for systemic absorption increases with the extent and activity

of the eczema. The main risk is suppression of the pituitary adrenal axis with possible

interference of growth in children. It is important to monitor the number, strength, and size of

tubes used between visits. This can indicate both excessive use and underuse of topical

preparations.

Type of preparation- Generally ointment bases is preferable to cream bases. The occlusive

effect of ointments results in better penetration of the corticosteroid and the incidence of irritant

and hypersensitivity reactions are reduced. This is mainly because preservatives are required in

creams but not in ointments.

Methods of application-Treatment should not be applied more than twice daily, and some of

the newer preparations require only once daily application. The large variation in the amounts

of topical steroids used by different patients can be minimised by specifying the quantity in

terms of fingertip units, where one fingertip unit equals 0.5 gm. Used intermittently, wet wrap

bandaging may be useful, especially in younger children. When steroids are used on the palms

51

and soles, or limited to very thicken lichenified areas of dermatitis, the effectiveness of topical

steroids can be enhanced by the use of impermeable or semi-permeable films.

Ichthammol and tar: The principal tars used for treatment of atopic dermatitis are ichthammol

and coal tar. Ichthammol is a derivative of shale and is less irritating than coal tars and may be

applied as an ointment (such as 1% ichthammol in zinc ointment) or in the form of paste

bandages, which can be particularly useful for healing lichenified eczema. Coal tar solution is

generally preferred to crude coal tar and in a strength of 1-10% may be added to

a variety of cream, ointment, or paste bases or it can be added to the bath.

Antihistamines: Until recently, antihistamines were a mainstay of therapy for the

ever-present itchiness of atopic dermatitis. Although antihistamines are still

prescribed by many dermatologists, allergists, and paediatricians, evidence-based clinical

studies have failed to demonstrate their efficacy58. This finding is not surprising because the

underlying immune response suggests cell-mediated immunity, in which symptoms are not

mediated by histamine but by lymphocyte secretions19. Nevertheless the therapeutic value of

antihistamines seems to reside principally in their sedative properties, and they are useful as a

short term adjuvant to topical treatment during relapses associated with severe pruritus. Non-

sedating antihistamines have little or no value in atopic dermatitis. The value of antihistamines

may be progressively reduced as a result of tachyphylaxis, and long term use is not

recommended. Night time use of sedative antihistamines, taken an hour or so before bedtime,

should be considered in any patient with atopic dermatitis who has difficulty getting to sleep,

who wakes regularly during the night, or who scratches while asleep. Daytime use should be

avoided.

Antibiotics: Antibiotics are important for treating overt secondary bacterial infection in

patients with atopic dermatitis. Flucloxacillin is usually the most appropriate antibiotic for

treating staphylococcus aureus, which is the commonest pathogen. Erythromycin may be used

52

when there is resistance to Flucloxacillin or in patients with a penicillin allergy. Use of topical

antibiotics should be restricted to limited areas. They are generally not ideal for treating

bacterial infections in patients with atopic dermatitis as patients often have widespread

secondary infection. Treatment of staphylococcal carrier sites prophylactically (such as the

nose, axillae, and perineum) with topical antibiotics may be appropriate in patients with

recurrent infected dermatitis56.

Eczema herpeticum responds to oral acyclovir, and the drug should be given early in the course

of the disease. In ill feverish patients, the acyclovir should be given intravenously.

Second-line treatment

The majority of patients will respond well to first line treatment regimen. Patients who fail to

respond should be reviewed to check compliance, to exclude antibiotic resistance, and to

consider second-line treatment27.

Intensive topical treatment: the strength of topical steroid treatment can be increased for a

short period as an outpatient. If this is ineffective, inpatient treatment will often control severe

exacerbations of dermatitis, the skin frequently improves using the same treatment that was

unsuccessful as an outpatient.

Wet-wrap technique: This can be useful technique for the control of severe atopic dermatitis

in younger children. Two layers of absorbent tubular bandage are applied to the skin. The inner

layer is pre-soaked in warm water and the outer layer is dry. A generous quantity of an emollient

(or a low potency topical corticosteroid in severe cases) is applied to the skin before the

dressings. The dressing can be used overnight or changed every 12 hours. This regimen can be

used in hospital or for short-term outpatient treatment. Close supervision should be maintained

because suppression of the hypo-thalamopituitary axis can occur when topical steroids are

employed.

53

Allergy management: In some cases changes in the diet or the environment may be helpful.

Investigation is rarely of value in these cases, and trials of allergen avoidance are usually

based on information obtained from a detailed history.

Allergen avoidance: Although house dust mites may have an important role in atopic eczema,

evidence for the benefits of eradicating mites is not strong, and currently there are no effective

measures for complete eradication. However, research is advancing rapidly and may clarify the

role of house dust mites in atopic dermatitis48.

The role of foods in initiating or perpetuating atopic dermatitis has been extensively

investigated but without reaching a conclusion46. A trial of dietary manipulation may be

indicated when a patient's history is strongly suggestive of a specific food allergy or when

widespread active atopic dermatitis is not responding to first line treatment. In general, dietary

restriction is of little or no benefit in adults with atopic dermatitis, and in children it is probably

infants who benefit most. In infants a four to six week trial excluding egg and milk with the

introduction of a hydrolysate infant formula may be justified, followed by a supervised

rechallenge. Professional dietetic advice and supervision is recommended. Immediate

hypersensitivity or type I reactions to foods can sometimes occur in patients with atopic

dermatitis, ranging from contact urticaria to anaphylaxis. It is important that parents and doctors

recognise such reactions and that the precipitating substance is avoided.

Phototherapy and photochemotherapy: Psoralens plus ultraviolet A (PUVA) and to a lesser

extent ultraviolet B have been found helpful in selected patients with atopic dermatitis. Some

concern exists, however, about the long term adverse effects such as premature skin aging and

cutaneous malignancies, particularly with PUVA, and it remains to be seen whether the benefits

outweigh the risks25.

54

Third-line treatment

Drug therapy: A number of systemic therapies are available in recalcitrant cases. Their

usefulness is restricted by limited effectiveness or concern over toxicity25.

Systemic corticosteroids have a limited but definite role in tiding occasional patients with

severe atopic dermatitis over crises. The decision to use systemic steroids should never be taken

lightly, and they should not be considered for maintenance treatment until all other avenues

have been explored. It is particularly important to try to avoid oral corticosteroids during rapid

adolescent growth, roughly 11-16 years in girls and 13-18 years in boys, to reduce the risk of

permanent growth retardation.

No conclusion was drawn from the data on evening primrose oil1. Two large trials have not

shown any evidence of benefit4, but other studies have reported benefit, particularly for patients

with moderate or severe eczema. If evening primrose oil is tried adequate doses should be

given--160-320 mg daily in children aged 1-12 years and 320-480 mg in adults for three months.

If no benefit is noted after three months it is unlikely to be helpful.

Low dose cyclosporine therapy has been shown to be effective in the control of adult atopic

dermatitis. Occasionally, permanent remission appears to be induced. Renal toxicity is the

limiting factor.

The value of oral sodium cromoglycate is still unclear, but high doses may be helpful in some

patients. Topical sodium cromoglycate has been helpful in children.

Several other drugs have been reported to be effective in atopic dermatitis. They include

55

interferon-gamma, thymopentin, type 4 phosphodiesterase inhibitors and topical tacrolimus and

pimecrolimus. Hepatotoxicity has been reported after administration of Chinese herbs. Patients

wishing to try Chinese herbs should be advised to have regular liver function tests.

Desensitization: This plays a very limited part in the management of patients with atopic

dermatitis, even when an allergic factor has been firmly established clinically. Such therapy is

effective in allergic rhinitis, and rather less convincingly in allergic asthma. It is also of value

in insect-sting anaphylaxis. However, deaths from anaphylactic reactions to immunization have

severely restricted its use in recent years.

Recent advances in the treatment of atopic dermatitis

Immunomodulators: Topical calcineurin inhibitors

The development of non-steroid topical immunosuppressant has been an historic development

in therapy of atopic dermatitis. Topical calcineurin inhibitors are an important class of

medications that have been shown to have clinical efficacy in atopic dermatitis, as displayed in

a broad set of clinical trials and in extensive clinical use56. Topical calcineurin inhibitors were

developed after the utility of systemic cyclosporin A, a potent inhibitor of T cells, was noted in

the treatment of eczematous dermatitis and psoriasis59. Cyclosporin A had been used for

prevention of organ transplant rejection after solid organ transplants and as a systemic

immunosuppressive for a broad set of conditions. Cyclosporin A is not useful as a topical

medication, presumably because of its large molecular size, which impedes its ability to

56

penetrate skin. Its use orally is associated with a risk of serious systemic effects, particularly

renal toxicity. Tacrolimus (FK 506) is another potent immunosuppressant used to prevent graft

rejection. Tacrolimus, however, is active topically and has been shown to be effective for

treatment of atopic dermatitis60, 61, 62. Pimecrolimus is an ascomycin derivative with potent

calcineurin inhibition developed specifically to treat inflammatory skin conditions, the result of

a prospective screening of hundreds of compounds63. It is approved for use in children as young

as two years of age or older with mild to moderate atopic dermattis64. Both tacrolimus and

pimecrolimus work through inhibition of phosphorylase activity of the calcium-dependent

serine/threonine phosphatase calcineurin and the dephosphorylation of the nuclear factor of

activated T-cell protein (NF-ATp).

Calcineurin inhibitor–steroid Combination therapy: Historically, combination therapies

with different classes of drugs have been used to maximize efficacy while managing the risk of

adverse events. Combining a calcineurin inhibitor and steroids should be no different in this

regard. Using a topical calcineurin inhibitor as a first-line pharmacologic agent for the treatment

of early signs and symptoms of AD, as opposed to treating only more severe exacerbations,

necessitates an excellent safety and tolerability profile to ensure practicability and compliance.

In this respect, neither skin atrophy nor hypothalamic-pituitary-adrenal axis suppression has

been observed with topical calcineurin inhibitors, making them more suitable than topical

steroids for frequent or prolonged use, especially on larger body surfaces or on areas especially

prone to atrophy with steroid use. With respect to clinical safety, data from studies of up to one

year duration showed comparable profiles for both calcineurin inhibitors65,66 , 67.

These recent advances provide the basis for future studies using early intervention with

combination/sequential treatment with topical calcineurin inhibitors and topical steroids to see

57

whether we can in fact impact not only the natural history of AD but interrupt the atopic march

as well56.

DISEASE PREVENTION AND OCCUPATIONAL ADVICE

Probiotics

Perinatal administration of the probiotic Lactobacillus rhamnosus strain GG has been shown to

reduce the incidence of atopic dermatitis in at-risk children during the first two years of life68.

The notion of probiotics use in primary prevention of atopic disease was based on their ability

to reverse increased intestinal permeability characteristic of children with atopic dermatitis and

food allergy. Probiotics also enhance gut-specific IgA responses, which are often defective in

children with food allergy. They also help to promote gut barrier function and restore normal

gut micro-ecology, alterations which have been shown in allergic individuals.

Maternal dietary restriction during pregnancy and lactation

There is conflicting evidence about whether maternal avoidance of milk, eggs and other dietary

allergens during the last trimester of pregnancy and during lactation could reduce the incidence

of atopic disorders, and there is inadequate evidence that breastfeeding or diets to avoid

potential allergens during the first six months of the infancy life will significantly protect

against atopy or reduce its manifestation1, 27. There is currently interest in reducing exposure to

dietary allergens, aeroallergens and irritants in children at high risk of developing atopic

manifestations. Some early evidence suggests that this approach may reduce the incidence of

atopic manifestations.

58

Occupational advice: Atopic dermatitis will often improve or go into remission at about the

time of puberty. This is often the time when adolescents are deciding what occupation they

should undertake. Exposure of the skin to irritant chemicals and physical trauma should be

avoided as far as possible. The reason being that 45% of patients that had childhood AD go on

to develop irritant contact dermatitis of the hand69. Adolescents with atopic dermatitis would

be well advised therefore to avoid occupations such as car mechanic, engineering, hairdressing

or nursing27.

59

CHAPTER THREE

PATIENTS AND METHOD

Area of study

The study was conducted in the dermatology clinic of Barau Dikko Specialist Hospital, Kaduna,

Kaduna state, Nigeria.

Kaduna is the capital city of Kaduna state, which is located in the north central zone of Nigeria.

It is made up of two local governments with a total population of 850,420 people70. The city is

both industrial and commercial. The residents are a mixed population of farmers, traders,

artisans, various professionals, politicians, civil servants, retired and serving military personnel

and students etc.

The dermatology clinic is one of the specialist clinics of Barau Dikko Specialist Hospital. The

clinic operates once a week and patients are seen on appointment basis except emergency cases.

The clinic attends to an average of fifty patients per week which translates to about 2,600 per

annum. Patients are usually referred from the general outpatient clinic of the hospital and all

the other specialist clinics of the hospital which include; children’s clinic, medical outpatient

clinic, the gynaecology clinic and the surgical outpatient clinic. Other sources of patients

include those referred from various health institutions in Kaduna metropolis and the

neighbouring states in the zone including Abuja.

The clinic is supervised by a Consultant Dermatologist who is a Fellow of the Medical College

of Physicians of Nigeria (FMCP).

60

Type of study

This is a Descriptive Cross-Sectional study that was carried out from July 2005 to December

2005. The study began in the middle of the rainy season and ended in the middle of the cold-

hamattan season. This was the period in which approval was given for the study.

Averages of ten new AD patients are seen per week with a total of about forty patients in a

month. Recruitment of patients was stopped when the sample size of 200 was attained.

Study population

The study population included all knew patients with atopic dermatitis presenting to the

dermatology clinic. The patients were recruited from among all the dermatological cases seen

in the clinic during the period of this study. The diagnosis of AD was established in all new

patients using the Revised Hanifin and Rajka diagnostic criteria that was clearly outlined

previously.

An informed written consent was obtained from all the patients that were recruited for the study.

Data was collected from patients’, patient relatives and patients’ parents in the case of children

using structured face-to-face interviewer questionnaire that was administered by the author. To

ensure confidentiality the questionnaires were not labelled.

Patients with disease conditions such as scabies, seborrheic dermatitis, allergic contact

dermatitis, cutaneous lymphoma, psoriasis, papular urticaria and pruritic papular eruptions due

to immune deficiency diseases, were excluded from the study. The distinguishing characteristic

features of these diseases have been discussed earlier in the text.

Sample size determination

61

As the population of the area of study is greater than 10,000 the following formula71 was used

to calculate and arrived at a sample size of 200;

N = Z 2 p q

d 2

Key:

N = is the desired sample size

Z = standard normal deviation usually set at 1.96 which corresponds to the 95% confidence

level.

P = the proportion in the target population estimated to have the particular characteristics

8.5% (0.85).

q = 1.0 – p (1.0 – 0.85 = 0.15)

d = degree of accuracy desired usually set at 0.05 or occasionally 0.02

In this study: Z = 1.96, p = 8.5% (0.85), q = 1.0 - 0.85 = 0.15, d = 0.05

N = 1.96× 1.96×0.85×0.15

0.05× 0.05

= 195 was the minimum sample size.

A sample size of 200 was used for the study.

Data analysis

Analysis was by computer using the Statistical Package for Social Sciences (SPSS) Microsoft

Software Version 12. A statistician was consulted throughout the period of data analysis.

The data was analysed with frequency distribution tables, bar charts, pictures and cross

tabulations. Chi Square test of statistical significance was determined where appropriate.

Ethical clearance

62

Ethical consent and clearance certificates were also obtained from the ethical committees of

Barau Dikko Specialist Hospital and 44 Nigerian Army Reference Hospital, Kaduna.

CHAPTER FOUR

63

RESULTS

A total of 1200 patients with various dermatological conditions were seen in the skin clinic of

Barau Dikko specialist hospital, Kaduna, during the period of this study from July 2005 to

December 2005. Out of these, 200 patients who satisfied the diagnostic criteria for atopic

dermatitis and consented were recruited for the study, thus giving a prevalence of 16.7%.

Age distribution of patients with atopic dermatitis

The age range was from 3 weeks to 55 years, with a mean age of 6.8 years (SD ± 10.8). Table

1 shows the age distribution of the patients. Patients in age range 0 – 12 years constituted 82.0%

while age range 13 – 64 years formed 18.0%.

Table 1: Age distribution of atopic dermatitis patients.

Age groups Number of patients %

0 - 5 months

6 - 11 months

1 - 5 years

6 - 12 years

13 - 19 years

20 - 39 years

40 - 64 years

53

34

49

28

4

28

4

26.5

17.0

24.5

14.0

2.0

14.0

2.0

Total 200 100

Sex distribution

64

The sex distribution of the 200 patients with AD is shown in table 2. More females 110 (55.0%)

were affected than males 90 (45.0%).

Table 2: Sex distribution of patients.

Sex of patients Number of patients %

Males

Females

90

110

45.0

55.0

Total 200 100

Educational status of the patients

65

One hundred and two (51.0%) of the patients were under nursery care, 48 (24.0%) patients were

in primary school, while 12 (6.0%) did not have any educational background (Table 3).

Table 3: Educational level of patients.

Level of education Number of patients %

Nursery

Primary

Secondary

Tertiary

Arabic

None

102

48

4

26

8

12

51.0

24.0

2.0

13.0

4.0

6.0

Total 200 100

Type of family

66

The types of family of the 200 patients are shown in figure 1. One hundred and sixty three

(81.5%) belonged to the nuclear family, 21 (10.5%) belonged to the extended type of family, 8

(4.0%) were living in a household, 4 (2.0%) patients each from a polygamous family and single

family.

Figure 1: The types of family the patients belonged to.

200

150

100

50

No of patients

0

Single family Nuclear family Extended family Household polygamous family

Types of Family

Occupation of patients

67

Figure 2 shows the occupation of the patients or parents where applicable. Sixty eight (34.0%)

patients were civil servants, 47 (23.5%) were traders, 13 (6.5%) were carpenters, 4 (2.0%) were

farmers, while 61 (30.5%) belonged to other professions which included the military and

paramilitary. Among the patients studied, 6 (3.0%) were unemployed.

Figure 2: Frequency of occupation of patients or their parents in case of children.

70

60

50

40

30

No

of 20

patients

10

0 Trading Farming Technician Civil servant Carpentry Others

Occupation

Monthly income

68

Figure 3 shows the monthly income of the 200 patients or their parents in the case of children.

68 (34.0%) patients earned over N25,000, 26 (13.0%) patients earned N15,000 to N20,000 and

25 (12.5%) earned N20,000 to N25,000. 21 (10.5%) patients each earned N5,000 to N10,000

and N10,000 to N15,000 respectively. 39 (19.5%) patients earned N5,000.

Figure 3: Frequency of monthly income of patients or their parents in the case of children.

70

60

50

40

30

20

No

10

of

patients

0

<or = N5,000 N5-10,000 N10-15,000 N15-20,000 N20-25,000 > N25,000

Monthly income

Age of onset of Atopic Dermatitis

69

The age of onset of AD is shown in table 4. Majority of the patients 167 (83.5%) developed AD

at infancy, 16 (8.0%) had their onset during childhood, only 2 (1.0%) had their onset at the

adolescence period while a significant number 15 (7.5%) had adult onset AD. The earliest age

of onset was 3 weeks in 4 (2.0%) of patients. The latest age of onset was 49 years in 4 (2.0%)

patients.

Table 4: Age of onset of Atopic Dermatitis

Age groups Number of patients %

0 – 11 months

1 - 12 years

13-19 years

20-49 years

167

16

2

15

83.5

8.0

1.0

7.5

Total 200 100

Duration of disease condition

70

The duration of the disease condition is shown in table 5. Among the 200 patients studied, 87

(43.5%) patients had recurring symptoms, 41 (20.5%) had the disease for weeks, 17 patients

(8.5%) had the symptoms for years while 30 (15%) of the patients had for months. 25 (12.5%)

could not remember the duration.

Table 5: Shows duration of disease condition

Duration of disease

condition

Number of patients %

Weeks

Months

Years

Goes and comes

back

Cannot remember

41

30

17

87

25

20.5

15.0

8.5

43.5

12.5

Total 200 100

Frequency of family history of atopy

71

Table 6 shows the frequency of family history of atopy. 172 patients (86%) had a family history

of atopy among them; asthma 65 (32.5%), allergic rhinitis 72 (36%), atopic dermatitis 14

(7.0%). 21 (10.5%) patients had all the atopic disorders in their family. There was no family

history of atopy in 28 patients (14.0 %,).

Table 6: Frequency of family history of atopy

Atopic disorders Number of patients %

Asthma

Allergic rhinitis

Atopic dermatitis

All atopic disorders

No history of atopy

65

72

14

21

28

32.5

36.0

7.0

10.5

14.0

Total 200 100

General physical condition of the patients on presentation

72

Table 7 shows the general physical conditions of the patients at presentation. Majority of the

patients were normal 190 (95.0%), while only 10 (5.0%) patients had abnormal general physical

conditions such as cervical lymphadenopathy, fever, acute illness and anaemia.

Table 7: General physical condition on presentation

Physical state at

Presentation

Number of patients %

Normal

Abnormal

Total

190

10

200

95.0

5.0

100

Distribution pattern of the rash of atopic dermatitis

73

Table 8 shows the pattern of distribution of the rash of atopic dermatitis. 76 (38.0%) of the

patients had lesions on the face, 64 (32.0%) patients had flexural involvement while 22 (11.0%)

patients had extensor involvement. 4 (2.0%) had palmo-plantar involvement. The neck was

involved in 20 (10.0%) patients, the abdomen was involved in 7 (3.5%) and the back in 5

patients (2.5%). 2 (1.0%) patients had nipple eczema.

Table 8: Distribution pattern of the rash of AD

Body region involved Number of patients %

Face

Flexural involvement

Extensor involvement

Neck

Abdomen

Back

Palmo-plantar

Nipple eczema

76

64

22

20

7

5

4

2

38.0

32.0

11.0

10.0

3.5

2.5

2.0

1.0

Total 200 100

Relationship of Age to the distribution pattern of the rash of AD

74

Table 9 (cross tabulation) shows the relationship of age to the distribution pattern of the rash of

atopic dermatitis. Seventy six patients in the age group 0-2 years show facial involvement while

45 patients in the age group >2-12 years show more of flexural involvement. Nipple

involvement was seen in 2 patients.

Table 9: Relationship of age to the distribution pattern of the rash of atopic dermatitis.

Body region involved

0 – 2 years

Age Groups

>2 – 12 years

% in bracket

>13 years

Total (%)

Facial involvement

Flexural involvement

Extensor ‘’

Neck

Abdomen

Back

Palmo-plantar

Nipple

Total

76 (38.0)

5 (2.5)

5 (2.5)

10 (5.0)

6 (3.0)

4 (2.0)

1 (0.5)

Nil

107(53.5)

Nil

45 (22.5)

11 (5.5)

5 (2.5)

1 (0.5)

1 (0.5)

3 (1.5)

Nil

66 (33.0)

Nil

17 (8.5)

6 (3.0)

5 (2.5)

Nil

Nil

Nil

2 (1.0)

30 (15.0)

76 (38.0)

67 (33.5)

22 (11.0)

20 (10.0)

7 (3.5)

5 (2.5)

4 (2.0)

2 (1.0)

203(101.5)

NOTE: A total of 203 (101.5%) was obtained because three patients had more than one body

region involved.

75

Picture 1 shows typical facial involvement in a 3 months old infant with characteristic erythema

and scaling (adapted from N Engl J Med 2005; 352: 2314-24.).

Picture 2 Miss N B, a 26 year old applicant, showing typical flexural involvement of the elbow

in AD. Note areas of hyperpigmented papular lichenified skin.

76

Picture 3 A R, a 6 year old female patient, showing extensive flexural involvement of the knees

in AD.

Picture 4 D G an 11 month old male patient, showing extensor involvement. The patient had

AD onset at 9 months when he started crawling. Note crusted plaque with few erythematous

papules.

77

Picture 5 HG, a 4 year old male patient,

showing chronic AD. The patient had a personal history of allergic conjunctivitis and family

history of asthma. Note areas of lichenified eczematous rash on the abdomen.

Picture 6 B M, an 8 year old male, showing palmo-plantar fissuring in the patient.

78

Table 10: The frequency distribution of morphology of the rash of atopic dermatitis.

Morphology of rash Number of patients %

Erythema

Papules

Lichenification

Scaling

Excoriation marks

Follicular lesions

Plaques

Secondary infections

Fissuring

Crusting and oozing

56

50

47

24

5

4

2

4

4

4

28.0

25.0

23.5

12.0

2.5

2.0

1.0

2.0

2.0

2.0

Total 200 100

79

The frequency distribution of the morphology of the rash of atopic dermatitis in the 200 patients

is shown in table 10 above. Fifty six patients (28%) presented with erythema, 50 (25%)

presented with papules while 47 (23.5%) presented with lichenification. Plaques were seen in

2 (1.0%) patients.

Provoking and exacerbating factors

The frequency distribution of the likely provoking factors of the disease is shown in table 11.

One hundred and eighty five (92.5%) patients or their parents in the case of children did not

know what provoked the rash. 7 (3.5%) patients attributed the appearance of the rash to change

of their bathing soap while 3 (1.5%) patients each after using nylon clothes and washing with

detergent and 2 (1.5%) patients after touching animals.

Table 11: The frequency distribution of the likely provoking factors.

Provoking factors Number of patients %

Change of soap

Nylon clothes

Touching animals

Washing with detergents

7

3

2

3

3.5

1.5

1.0

1.5

80

No idea 185 92.5

Total 200 100

The frequency distribution of the likely exacerbating factors is shown in table 12. Majority of

the patients 133 (66.5%) or parents did not know the exacerbating factors, 20 (10.0%) attributed

their exacerbation to using medicated soaps while 40 (20.0%) were new patients (AD occurring

for the first time).

Table 12: The frequency distribution of likely exacerbating factors.

Exacerbating factors Number of patients %

Anger

Over work/play (sweating)

Adverse conditions

Eating groundnuts

Medicated soaps

New patients

No idea

Nil

5

Nil

2

20

40

133

-

2.5

-

1.0

10.0

20.0

66.5

Total 200 100

81

Exacerbation of atopic dermatitis in relation to season

Table 13 shows the severity/exacerbation of AD in relation to season. 35 (17.5%) patients had

exacerbation or worsening during hamattan season, 22 (11.0%) patients during rainy season, 3

(1.5%) patients during dry-hot season, 30 (15.0%) patients claimed to be during all seasons, 40

(20.0%) were new patients (AD occurring for the first time) and 70 (35.0%) patients could not

relate their problems to any season.

Table13: Exacerbation of AD in relation to season

Seasons Number of patients %

Hamattan

Rainy season

Hot-dry season

During all seasons

New patients

No idea

35

22

3

30

40

70

17.5

11.0

1.5

15.0

20.0

35.0

Total 200 100

82

Table 14 shows the distribution of patients that have pets or poultry at home. One hundred and

seventy eight patients (89.0%) did not have either a pet or poultry at home while 22 (11%) had

a pet or poultry but rarely come into contact with the animals.

Table 14: Presence of Home pets or poultry among the patients with AD

Presence of pet or poultry Number of patients %

No

Yes

178

22

89.0

11.0

Total 200 100

Health seeking pattern of patients on first appearance of the rash of AD

Table 15 shows the health seeking pattern of patients or their parents in the case of children

when they had atopic dermatitis for the first time. 72 (36.0%) patients consulted the herbalist

because they believe that only native medicine can cure the disease, 47 (23.5%) patients

consulted the doctor because they see the doctor for all medical problems, 34 (17.0%) visited

the patent medicine vendors either because it was cheaper or nearer to their houses, 21 (10.5%)

did nothing because they believed it was either due to heat or change of water, 12 (6.0%)

patients consulted the pharmacist, a sizeable number of patients 14 (7.0%) used either honey,

dettol or powder which they believed could cure it.

Table 15: Health seeking pattern of patients on first appearance of the rash of AD

Health seeking on first

appearance of the rash of AD

Number of patients %

83

Visited patent medicine vendor

Consulted the herbalist

Consulted the pharmacist

Consulted the doctor

Did nothing

Others Applied honey

‘’ dettol

‘’ powder

34

72

12

47

21

14

17.0

36.0

6.0

23.5

10.5

7.0

Total 200 100

Table 16 shows distribution of the nature of medications used on first appearance of AD before

reporting to our skin clinic. One hundred and seventy nine (89.5%) patients used some form of

medication while 21 (10.5%) did not use any.

Table 16: Nature of medication used on first appearance of AD

Nature of medication Number of patients %

Herbs

Tablets and/or creams

Others Moju cream

Nycil powder

Honey

Dettol

No medication

72

73

34

21

36.0

36.5

17.0

10.5

Total 200 100

84

Table 17: Outcome of treatment in patients that had medications

Outcome of disease Number of patients %

Improved and relapsed

Improved

No improvement

Worsened

No medication

108

21

40

10

21

54.0

10.5

20.0

5.0

10.5

Total 200 100

Table 17 shows the distribution of outcome of treatment in patients that had some form of

treatment and in patients without treatment before reporting to our clinic. Majority of the

patients 108 (54.0%) had improvement with relapse, 21 (10.5%) patients improved and 10

(5.0%) had their disease worsened. There was no improvement in 40 (20.0%) patients.

Table 18: Relationship of monthly earning of patients to health seeking pattern

< Monthly Earning of patients or parents >

Health

seeking

< or =

N5,000

N5,000

to

N10,000

N10,000

to

N15,000

N15,000

to

N20,000

N20,000

to

N25,000

>N25,000

Total

Medicine

Vendor

5

2

4

6

5

12

34

Herbalist 14 8 8 8 10 24 72

Pharmacy 20 3 2 2 1 6 11

Doctor 13 3 4 3 4 18 45

85

Nothing 3 4 1 4 3 6 21

Others 2 1 2 3 2 2 12

Total 39 21 21 26 25 68 200

Table 18 shows the relationship of the monthly earning of patients or parents in case of children.

X2 = ∑(0-E)2 key

_______ O= Observed Value

E E= Expected Value

df = (c-1)(r-1) c= column

r = row

df = degree of freedom

X2 = 0.795 using computer to calculate, df = 25 at p value 0.05 = 37.6525 which is far more

than 0.795.

Chi square (x2) test with significance value 0.795 indicating that the health seeking pattern of

patients when AD appeared for the first time is independent of their monthly earning at p value

(level of significance) = 0.05

Patients’ response to the likely causes of the disease

Table 19 shows the patients’ responses as to the likely cause of the disease. 160 (80%) patients

did not know what caused the disease while 40 (20%) patients gave various reasons.

Table 19: Patients’ responses to the likely cause of AD

Likely cause of disease Number of patients %

Did not know

Others Scabies

Heat

From God

160

40

80.0

20.0

86

Eating sugary foods

during pregnancy

Change of water

Total 200 100

CHAPTER FIVE

DISCUSSION

The prevalence of AD in this study was 16.7%. Our report was based on hospital outpatient

data and interestingly, the prevalence obtained is much higher than that found in a similar study

in Singapore which was also hospital outpatient based, with prevalence of 2%72. This figure is

much higher than 3.5%, 6.1% and 8.5% being the prevalence rates of AD reported in south-

western Nigeria in 1986, 1989 and in the south-east in 2004 by Olumide11, George12 and

Nnoruka14 respectively. This can probably be explained by the rapid urbanization, changes in

lifestyle experienced by the average Nigerian family and an increasing accessibility to health

services. Nevertheless, this value falls within the values reported in the western literature, which

are usually between 10 and 30%7. It is thought that the actual prevalence is higher in the

community, as many cases of AD, especially the milder cases, present initially to general

practitioners. Onadeko13 provided data on Nigeria (Ibadan, western Nigeria) for the

87

International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee Report

on 463 801 children aged 13–14 years from 56 countries in 1996. In their study, the prevalence

of AD symptoms showed Nigeria among the top three on the list with 17%. However, it was a

questionnaire based study of school children aged between 13 and 14 years old and included

questions based on the presence of flexural itchy rash. The ISAAC study13 also shows that,

where different regions of the same country are studied, as in Kenya, widely differing

prevalence may be found. This may also be the case for Nigeria, as it is a wide country.

Atopic dermatitis is predominantly a disease of infancy and childhood2, 3, 14. A similar finding

was observed in this study with majority (82.0%,) of the patients in the age range of 0 to 12

years. There is no definite reason for this but it is thought that children are exposed to some

antigens for the first time in life.

In this study, more females were affected than males, in a ratio of 1.2:1. This agrees with earlier

studies carried out by Nnoruka14 in Nigeria as well as by Tay and colleagues72 whose study was

based on Caucasians. However, sex distribution has not been consistent3, 8. This is evidenced

by the work of Yemaneberhan and colleagues73 in Ethiopia where they found more males being

affected than their female counterparts in a ratio of 1.5:1 while Larsen in a survey on northern

Europe8 found a male to female ratio of 1:1.

Majority of the patients (81.5%,) in this study belonged to the nuclear family which is in

agreement with what was reported by Williams5 that AD is commoner in smaller families.

Despite decades of extensive research, no definite reason was found.

88

It was found that 33.5% of the patients earned over N 25, 000 monthly (the minimum earning

of a newly employed university graduate or salary grade level 8) and these were presumed to

be in the higher socio-economic groups. AD is commoner in those from higher socio-economic

groups5. Better housing and affluent living are more likely to expose individuals to house dust

mite which are speculated to be associated with higher occurrences of AD.

The earliest age of onset in this study was 3 weeks which is slightly earlier than what Nnoruka14

found in south-eastern Nigeria where she obtained 4 weeks as the earliest age of onset. However

AD can appear even at age 2 weeks27. The latest age of onset was 49 years which conforms to

what was reported by Beltrani49 that it is rare to see AD after mid life (fifty years of age).

Majority of the patients 83.5% experience the development of their disease before their first

birthday which is slightly higher than the 60% reported by Beltrani49. Adult onset (after the age

of 21 years) is said to be uncommon, constituting only about 2.4% of cases as reported by

Beltrani49. 7.5% of the patients in this study had their onset between 20 to 49 years. This figure

is less than but similar to another study in Singapore, where 13.6% of patients had onset of

atopic dermatitis after the age of 21 years72.

Atopic dermatitis typically has a recurring and relapsing nature1. 43.5% of the patients in this

study reported that their disease was recurring in nature. The exact mechanism of this

phenomenon is unknown.

A family history of atopy is found in 70% to 90% of patients with AD; those cases without a

family history do not differ materially from the remainder, although they have a somewhat

better prognosis 33. Inconsistent results have been obtained from studies of the Human

Leucocytes Antigen (HLA) complex haplotypes regarding the family history44.One hundred

89

and seventy two patients (86%) had a family history of atopy, while 14% had no history of

atopy. Allergic rhinitis was commoner in these families (36%). Nnoruka14 in south-eastern

Nigeria found a family history of atopy in 52.5% of patients with asthma being the commonest.

Our findings are slightly higher than those found by Tay and colleagues72 whose study revealed

that 47% of their patients had a family history of atopy while 53% had no family history of

atopy, but their finding agrees with ours on allergic rhinitis.

The finding of erythema, papules and scaling in 64% of the patients at presentation indicate

subacute dermatitis; lichenification in 23.5% is a feature of chronic dermatitis while the findings

of excoriation marks, crusting and oozing with secondary bacterial infection in 13% of the

patients signify acute dermatitis. These findings are similar to what Tay and colleagues72 found

in Singapore. The frequencies of the associated clinical conditions such as fissuring and

follicular lesions were quite uncommon in this study. Weather and racial factors may be

responsible.

Facial involvement was observed in 38% of the patients in this study. This is because the rash

of AD in infants is commonly found on the face69 and 43.5% of the patients were under one

year of age. 32% of the patients presented with involvement of the flexural folds of the body

which is in sharp contrast with the findings of Nnoruka14 where extensor regions of the body

was involved in 70%. Hot humid weather of south eastern Nigeria may be a possible reason.

The age group 0 to 2 years show more of facial involvements while those who are 2 years and

above show more of flexural involvement and no obvious reason have been found. This finding

is in agreement with what Nnoruka14 found in Nigeria and in what has been reported in the

western literature49.

90

Ninety two and half percent of the patients in this study did not know the likely provoking

factors of their disease. The lack of awareness of atopic dermatitis in our environment may

likely be responsible. 7.5% of the patients attributed provocation of their disease to change of

soap, using nylon clothes or washing with detergent which agrees with the findings of other

authors49. 66% of the patients did not know the exacerbating factors of their disease. 20%

attributed the exacerbation to the use of medicated soaps. This is likely due to the irritant nature

of the active ingredients of medicated soaps which can easily provoke itching. Those patients

that had AD for a short period did not have the disease long enough and therefore unlikely to

have observed the exacerbating factors. 17.5% of the patients attributed the exacerbation of

their symptoms to the hamattan season. This finding does not agree with the ISAAC study

findings that cold weather is associated with the rising prevalence of AD4. However, a hospital

based study like ours is not likely to give the true picture of what is obtainable in the community

as the ISAAC study was community based. Only 1.5% of the patients reported exacerbation

during the hot-dry season which is in contrast to the findings of Nnoruka14 in the south-eastern

part of Nigeria where 38% of their patients had exacerbation during hot humid periods.

Geographical variation, sample size and study design maybe responsible for the differences.

Eighty nine percent of the patients in this study did not own a pet or poultry and even the 11%

that own one rarely came into contact with the animals. This finding is in agreement with cross-

sectional studies from Sweden73 and Ethiopia74 where no significant association between

exposure to domestic animals and AD risk at age 7–11 years was found.

Atopic dermatitis can be very distressing to the patient or his family thereby seeking alternative

and complimentary therapy. 36% of the patients in this study consulted the herbalist for

alternative medications. Western literature reported that there is conflicting evidence regarding

efficacy and potential concerns regarding hepatic and other toxicities of (Chinese) herbal

91

therapy for AD1, 27, 49. The various health seeking measures adopted by our patients on first

appearance of AD and the outcome indicate the level of ignorance, desperation and confusion

about the disease in our environment. It was similarly observed that the health seeking

behaviour of the patients is independent of their monthly earning (x2 0.795).

Eighty percent of the patients in this study did not know what causes atopic dermatitis while

the remaining 20% gave various reasons ranging from heat to scabies and to eating sugary foods

during pregnancy. This finding is in agreement with what is reported in the western literature

that despite decades of research the exact cause of AD is still unknown19.

For the management of AD patients in our environment, low socioeconomic status and poor

health care-seeking behaviour created a challenge. A similar challenge was met by Nnoruka14.

However most of the patients were treated with mildly potent steroids such as 1%

hydrocortisone and advice on the use of emollients. The common emollients in our environment

are products of petroleum jelly. Those patients with extensive lichenification and fissuring,

antikeratolytic agents such as salicylic acid were added to their treatment. The few patients that

had secondary bacterial infections were treated with broad spectrum antibiotic such as oral

ampiclox and erythromycin. The entire patients had sufficient health education and advice on

the likely provoking and exacerbating factors and the seasonal variations.

92

LIMITATIONS AND CONSTRAINTS OF THE STUDY

a) There was no facility to determine IgE reactivity which though not essential but

sometimes an important diagnostic feature of AD (see diagnostic criteria). IgE reactivity

is found in only about 20% to 40% of patients with atopic dermatitis.

b) There is a dearth of local literature on AD from this environment. Some of the few

studies carried out in the southern part of Nigeria are old with the exception of the one

from Enugu. Foreign literature cited were accessed through HINARI (Health

Internetworking Access to Research Initiative), a WHO (World Health Organisation)

website developed for developing countries.

93

c) This is a hospital-based study. The prevalence of AD in the community maybe higher

and some of the associated clinical features that were not observed in our study may be

found in the community.

d) There was funding constraints as the author had to bear the whole cost of the study.

RECOMMENDATIONS

1. It was observed from this study that the prevalence of atopic dermatitis is high among

dermatology clinic attendees in Kaduna when compared with their counterparts in

Enugu, south-eastern Nigeria. The author therefore, recommends that health care

providers and stake holders in the health sector should collaborate and determine its

prevalence in the community which is more representative than a hospital survey.

2. From the information obtained from the health seeking pattern of the patients studied,

the author also recommends that further studies be conducted at the family level to

determine the cost implication of atopic dermatitis to families in Nigeria.

3. Based on the finding that majority of our patients or parents as the case maybe did not

know the cause of atopic dermatitis, extensive public enlightment programmes to

94

improve awareness on this disease would go a long way in reducing its burden especially

to mothers.

4. The author recommends that periodic continuing medical education (CME) on AD be

organised for frontline doctors because of the very few dermatologists in our

environment.

5. It is also recommended that stake holders in the health sector liaise with the local

community to adopt a local name for AD.

6. There is the need for more clinical and multi-centre research on this disorder by family

physicians and dermatologist especially in the area of its management.

7. The Nigerian government through the National Institute for Pharmaceutical Research

should collaborate with the Traditional Medicine Healers with a view to determining

the pharmacotherapeutic value and purity of the local herbs used in achieving some

form of remission in atopic dermatitis patients.

REFERENCES

1. Hanifin JM, Cooper KD, Vincent CH, Kang S, Krafchik BR, Margolis DJ et al.

Guidelines of care for atopic dermatitis. J Am Acad Dermatology 2004; 50: 391-404.

2. Williams HC. Epidemiology of atopic dermatitis. Clin Experimental Dermatol 2000;

25(7): 522.

3. Kay J, Gawkrodger DJ, Mortimer MJ and Jaron AG. The prevalence of childhood

atopic eczema in a general population. J Am Acad Dermatol. 1994; 30: 9-28.

4. International Study on Asthma and Allergies in Childhood (ISAAC) Steering

committee. World wide variation in prevalence of symptoms of asthma,

rhinoconjuctivitis and atopic eczema. International Study on Asthma and Allergies in

Childhood: Lancet 1998; 351: 1225-1232.

95

5. Williams HC. Atopic eczema-why we should look to the environment. BMJ 1995;

311(7015): 1241-2.

6. Strachan DP. Hay fever, hygiene, and household size. BMJ 1989; 299: 1259-60.

7. Larsen FS and Hanifin JM. Epidemiology of atopic dermatitis. Immunol Allergy Clinics

NA 2002; 22: 1-25.

8. Larsen SF, Diepgen T and Svensson A. The occurrence of atopic dermatitis in north

Europe: an international questionnaire study. J Am Acad Dermatol 1996; 34: 760-4.

9. Leung DY, Diaz LA, DeLeo V and Soter NA. Allergic and immunologic skin diseases.

JAMA 1997; 278(22).

10. Sugiura H, Umemoto N and Deuichi H. Prevalence of childhood and adolescent atopic

dermatitis in a Japanese population: Comparison with the disease frequency examined

20 years ago. Acta Derm Venereol (stockh) 1998; 78: 293-4.

11. Olumide YM. The incidence of atopic dermatitis in Nigeria. Int J Dermatol 1986;

26:376.

12. George AO. Atopic dermatitis in Nigeria. Int J Dermatol 1989; 28: 237-239.

13. Williams H, Robertson C, Stewart A, Aït-Khaled N, Anabwani G, Onadeko et al.

Worldwide variations in the prevalence of symptoms of atopic eczema in the

international study of asthma and allergies in childhood. J Allergy Clin Immunol 1999;

103:125-38.

14. Nnoruka EN. Current epidemiology of atopic dermatitis in south-eastern Nigeria. Int J

Dermatol 2004; 43(10): 739-744.

15. Donald T. M. Leung. Pathogenesis of atopic dermatitis. J Allergy Clin Immunol 1999;

104(3): S99-108.

16. Lawrence F, Hanifin JM, Thomas AL, Seth RS and Howard BP. Consensus conference

on paediatric atopic dermatitis. J Am Acad Dermatol 2003; 49(6): 1088-95.

96

17. Emerson RM, Charman CR, Williams HC. The Nottingham Eczema Severity Score:

Preliminary refinement of the Rajka and Langeland grading. Br J Dermatol 2000; 142:

288-97.

18. Popescu CM, Popescu R, Williams HC, et al. Community validation for the UK

diagnostic criteria for atopic dermatitis in Romanian schoolchildren. Br J Dermatol

1998; 138: 436-42.

19. Leicht S and Hanggi M. Atopic dermatitis: how to incorporate advances in management.

Postgrad Med 2001; 109(6): 119-27.

20. Lapidu CS, Schwarz DF, Honig PJ et al. Atopic dermatitis in children: Who cares? Who

pays? J Am Acad Dermatol 1993; 28: 699-703.

21. Su JC, Kemp AS, Varigos GA and Nolan TM. Atopic eczema: its impact on the family

and financial cost. Arch Dis Child 1997; 76(2): 159-162.

22. Fennessy M, Coupland S, Popay Jand Naysmith K. The epidemiology and experience

of atopic eczema during childhood: A discussion paper on the implication of current

knowledge for health care, public health policy and research. J Epidemiol Community

Health 2000; 54(8): 581-589.

23. Emerson RM, Williams HC and Allen BR. What is the cost of atopic dermatitis in

preschool children? Br J Dermatol 2001; 144: 449-651.

24. Herd RM, Tidman MJ, Prescott RJ and Hunter JJN. The cost of atopic eczema. Br J

Dermtol 1996; 135: 20-23.

25. McHenry PM, Williams HC and Bingham EA. Fortnightly Review: Management of

atopic eczema. BMJ April 1995; 310: 843-847.

26. Wise F, Sulzberger MB. Editorial remarks. In: Yearbook of dermatology, syphilology.

Chicago: Yearbook Medical Publishers; 1933. pp. 31–70.

97

27. Holden CA and Parish WE. Atopic dermatitis. In: Champion RH, Burton JL, Burns DA

and Breathnach, editors. A Rook, DS Wilkinson and FJG Ebling Textbook of

dermatology, 6th Ed. Blackwell Scientific Publication, Oxford 1998. p. 681–708.

28. Becker LE. Elements of the history of our present concepts of anaphylaxis, hay fever

and asthma. Clin Experimental Allergy 1999; 29: 875–895.

29. Hanifin JM and Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol

1980; 92: 44–47.

30. William HC, Burney PG, Pembroke AC and Hay RJ. Validation of the U.K. diagnostic

criteria for atopic dermatitis in a population setting. Br J Dermatol 1996; 135: 12-17.

31. Gibbs S. skin diseases and socioeconomic conditions in rural Africa: Tanzania. Int J

Dermatol 1996; 35: 633-639.

32. Emerson R, Williams HC, Allen BR. Severity distribution of atopic dermatitis in the

community and its relationship to secondary referral. Br. J. Dermatol. 1997: 137

(suppl.50): 23.

33. Rothe MJ and Grant-Kels JM. Atopic dermatitis: an update. J Am Acad Dermatol 1996;

35(1): 1-13.

34. Moffatt MF and Cookson WO. The genetics of asthma. Maternal effects in atopic

disease. Clin Exp Allergy 1998; 28 (suppl 1):56–61.

35. Wadonda-Kabondo N, Sterne JAC, Golding J, Kennedy CTC, Archer CB and Dunnill

MGS. Association of parental eczema, hay fever, and asthma with atopic dermatitis in

infancy: birth cohort study. Arch Dis Childhood 2004; 89: 917-921.

36. Berth-Jones J, George S and Graham-Brown RAC. Predictors of atopic dermatitis in

Leicester children. Br J Dermatol 1997; 136: 498-501.

37. Fergusson DM and Horward LJ. Early solid food diet and atopic dermatitis in childhood.

Paediatric Allergy Immunol 1994; 5(S1): 44-47.

98

38. Tan B, Weald D, Strickland I and Friedmann R. Double-blind controlled trial of effect

of house dust mite allergen avoidance on atopic dermatitis. Lancet 1996; 347: 15-18.

39. McNally NJ, Williams HC, Phillips DR et al. Atopic eczema and domestic water

hardness. Lancet 1998; 352: 527–31.

40. Leung R and Ho P. Asthma, allergy and atopy in three South-East Asian populations.

Thorax 1994; 49: 1205–10.

41. Pöysä L, Korppi M, Pietikäinen M, Remes K Juntunen-Backman K. Asthma, allergic

rhinitis and atopic eczema in Finnish children and adolescents. Allergy 1991; 46:161-5.

42. Kjellman B, Petterson R and Hyensjö B. Allergy among school children in a Swedish

county. Allergy 1982; 37: 5–6.

43. Agata H, Kondo N, Fukutomi O et al. Comparison of allergic diseases and specific IgE

antibodies in different parts of Japan. Ann Allergy 1994; 72: 447–51.

44. Diepgen TL and Blottner M. Analysis of familial aggregation of atopic dermatitis and

the other atopic diseases by odds ratio regression models. J Invest Dermatol 1996; 106:

977-81.

45. Hayer G, Ulmer F and Schmitz L. Histamine-induced itch and allokinesis (itchy skin)

in atopic dermatitis patients and controls. Acta Derm Venereol (Stoch) 1995;75:348-52.

46. Sicherer SH and Sampson HA. Food hypersensitivity and atopic dermatitis:

Pathophysiology, epidemiology, diagnosis and management. J Allergy Clin Immunol

1999; 104: S114-22.

47. Sherriff A, Golding J and The Alspac Study Team. Hygiene levels in a contemporary

population cohort are associated with wheezing and atopic eczema in preschool infants.

Arch Dis Childhood 2002; 87: 26-29.

48. Flohr C, Pascoe D and Williams HC. Atopic dermatitis and the 'hygiene hypothesis': too

clean to be true? Br J Dermatol 2005; 152(2): 202-216.

99

49. Beltrani VS. The clinical spectrum of atopic dermatitis. J Allergy Clin Immunol 1999;

104, 3(Suppl1): S87-S98.

50. Machara WM, Anabwani GM and Onili DM. Clinical presentation of atopic dermatitis

in Negroid children. Afri J Med Sci 1993; 22: 41-44.

51. Lawson V, Lewis-Jones MS, Reid P et al. Family impact of childhood eczema. Br J

Dermatol 1995; 133(suppl 45): 19.

52. Mosgrove K and Morgan JK. Infantile eczema. Br J Dermatol 1995(1976): 365-372.

53. Wuthrich B. Epidemiology and natural history of atopic dermatitis. Allergy clin

Immunol International 1996; 8: 77-82.

54. Jonathan MS and Paller AS. Atopic dermatitis and the atopic march. J Allergy Clin

Immunol 2003; 112: S118-27.

55. Williams HC. Atopic Dermatitis. N Engl J Med 2005; 352: 2314-24.

56. Boguniewicz M, Eichenfield LF and Thomas H. Current management of atopic

dermatitis and interruption of the atopic march. J Allergy Clin Immunol 2003; 112:

S140-50.

57. Peter JB. New directions in allergic diseases: Mechanism-based anti-inflammatory

Therapies. J Allergy Clin Immunol 2000; 106: 5-16.

58. Peter AK and Richard AFC. An evidence-based review of the efficacy of antihistamines

in relieving pruritus in atopic dermatitis. Arch Dermatol 1999; 135 (12):1522-1525.

59. Berth-Jones J, Graham-Brown RAC, Marks R, Camp RDR, English JSC, Freeman K

et. al. Long-term efficacy and safety of cyclosporin in severe adult atopic dermatitis. Br

J Dermatol 1997; 136: 76-81.

60. Bekersky I, William F, Atsushi T, Rochelle MM, Ellen H and I Lawrence. Non-clinical

and early clinical development of tacrolimus ointment for the treatment of atopic

dermatitis. J Am Acad Dermatol 2001; 44(1): S17-27.

100

61. Boguniewicz M, Virginia CF, Sharon R, Ira DL, Donald YML and Hanifin JM. A

randomized, vehicle-controlled trial of tacrolimus ointment for treatment of atopic

dermatitis in children. J Allergy Clin Immunol 1998; 102: 637-44.

62. Paller A, Eichenfield LF, Leung DYM, Daniel S and Appell M. A 12-week study of

tacrolimus ointment for the treatment of atopic dermatitis in paediatric patients. J Am

Acad Dermatol 2001; 44: S47-57.

63. Meingassner JG. A novel anti-inflammatory drug. Br J Dermatol 1997; 137: 568-76.

64. Eichenfield LF and Lisa B. Elidel (pimecrolimus) cream 1%: A non-steroidal topical

agent for the treatment of atopic dermatitis. J Allergy Clin Immunol 2003;111(5):1154-68.

65. Sakari R, Andreas W, Erwin S, Jean LP, Ronald M, Thomas R et. al. Safety and efficacy

of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. Arch

Dermatol 2000; 136(8): 999-1006.

66. Wahn U, Bos JD, Goodfield M, Caputo R, Papp K, Ahmed M et. al. Efficacy and safety

of pimecrolimus cream in the long-term management of atopic dermatitis in children

efficacy and safety of tacrolimus in children. Paediatrics 2002; 110: e2.

67. Meurer P. Pimecrolimus. Dermatology 2002; 205: 271-277.

68. Kalliomäki M, Seppo S, Heikki A, Pentti K, Pertti K, Erika I et al. Probiotics in primary

prevention of atopic disease: a randomised placebo-controlled trial. Lancet 2001; 357:

1076–79.

69. Thestrup-Pedersen K. Clinical aspects of atopic dermatitis. Clinical and Experimental

Dermatology 2000; 25(7): 535-543.

70. National Population Commission, 1991.

71. Araoye OM. Sample size determination. Research Methodology, 1st Ed. Ilorin,

Nathadex Publishers 2003; 117-118.

101

72. Tay Y-K, Khoo B-P, Goh C-L. The profile of atopic dermatitis in a tertiary dermatology

outpatient clinic in Singapore. Int J Dermatol 1999; 38: 689–692.

73. Yemaneberhan H, Flohr C, Lewis S, Bekele Z, Parry E, Williams HC et al. Prevalence

and associated factors of atopic dermatitis symptoms in rural and urban Ethiopia. Clin

Exp Allergy 2004; 34:779–785.

74. Bråbäck L, Kjellman NI, Sandin A, Björkstén B. Atopy among schoolchildren in

northern and southern Sweden in relation to pet ownership and early life events.

Pediatr Allergy Immunol 2001; 12: 4–10.

ANNEX 1 QUESTIONNAIRE

A questionnaire on Atopic dermatitis (a form of skin disease that itches and usually run in

families). You are please required to answer questions in the first part while the doctor will

examine you and answer the other questions. Please respond to the answers of your choice and

leave those you don’t know or are not applicable to you or your child. All information provided

would be treated with utmost confidentiality.

SECTION A:

1.0 FAMILY AND SOCIAL HISTORY

1.1 Age of the patient

a)…… weeks b)…… months c)…… years

1.2 Sex? male female

1.3 Marital status

a) single b) married c) divorced d) widow e) separated

1.4 What is your level of education or of your child?

a) primary b) secondary c) tertiary d) Arabic e) nursery f) others (specify)

1.5 What is your occupation or of your parent?

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a) trading b) farming c) technician d) civil servant e) carpentry f) others (specify)…

1.6 How much do you earn in a month please approximate

a) N5000 and below b) N5, 000 – N10, 000 c) N10, 000 – N15, 000

d) N15, 000 - N20, 000 e) N20, 000 – N25, 000 f) over N25, 000 1.7 What type of family do you belong to?

a) Single family (mother or father only & children).

b) Mother and Father with children

c) Extended family (grandparents, uncles, cousins all living together)

d) Household (groups of people eating from the same pot)

1.8 Do you have cats or dogs or poultry in your house? a) yes b) no

2.0 PRESENTATION

2.1 At what age did you first notice this rash?

a)…..weeks b)….months c)….years d)….cannot remember

2.2 How long have you had this rash or your child?

a)…weeks b) …months c) …years d) goes and comes back e) cannot remember

2.3 Does your grandparents, parents, sisters or brothers have any of the following?

a) asthma b) itching eyes c) frequent sneezing in the mornings d) itching of the

skin e) all these.

2.4 Which areas of the body do you have the rash

a) the face b) the elbows c) the wrist only d) the knees only e) the face, elbows,

wrist and knees f) the eyelids g) the scalp h) feet i) neck j) buttocks

k) around the private part area l) others(specify)

2.5 Do you have or your child (you can select more than one option)?

a) very itchy skin b) redness of the skin c) very thick skin d) very dry skin

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3.0 PROVOKING FACTORS

3.1 Does the rash appear or increase after using?

a) soaps b) creams c) touching chemicals d) inhaling something(specify) e)after

eating something (specify) f) particular clothing g) touching grass h) touching

animals i) others (specify)…

3.2 Does the rash appear after any of the following conditions?

a) anger b) family conflict c) over work

d) adverse social conditions (e.g. no electricity, no water) e) others(specify)

3.3 What time of the year is the rash worse?

a) hamattan b) rainy season c) hot season d) during all these seasons

4.0 HEALTH SEEKING PATTERN

4.1 What did you do when the rash appeared for the first time?

a) Visited the patent medicine vendor b) consulted the herbalist c) did nothing

d) consulted the pharmacist e) consulted the doctor f) consulted the dermatologist g)

went to prayer house h) others(specify)

4.2 Reason (s) for the choice in question 4.1

a) it will go by itself b) it is cheaper c) it is nearer to my house or work place

c) usually see the doctor for all medical problems e) I was referred

f) the problem was spiritual g) others(specify)

4.3 Did you use any medication? a) yes b) no (if yes proceed to Q4.4)

4.4 What medication did you use?

a) herbs or their oil b) red oil c) engine oil d) nothing e) tablets and/or creams

f) health education. g) others(specify)…

4.5 Did your rash improved?

a) yes b) no c) worsened d) improved and reappeared

4.6 What do you think caused these rashes?

a) I don’t know b) evil spirit c) inherited from my parents d) my soaps and creams

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e) my cloths (including napkins) F) others (specify

SECTION B: CLINICAL EXAMINATION

5.0 General Physical Examination

a) Pallor b) Temperature c) Peripheral lymph nodes d) normal f) other findings (state)

6.0 Skin Examination

6.1 Distribution of rash (can select more than one option)

A) face b) eyelids c) flexor elbow d) extensor elbow e) wrist f) neck g) buttocks

h) popliteal area i) chest J) abdomen k) back l) others (specify)

6.2 Morphology of rash

a) erythema b) papules c) vesicle d) crust e) ooze f) excoriation marks g) ulcers

h) follicular lesions i) scaling j) lichenification k) secondary infections l) dryness

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ANNEX II CONSENT FORM

PATIENT CONSENT FORM

My name is DR Mijinyawa I am a Senior Registrar with the Department of Family Medicine,

44 Nigerian Army Reference Hospital, Kaduna. I am conducting a study on a skin disease called

Atopic Dermatitis.

Your permission is needed in order to include you or your child in the study. All information

provided would be treated with utmost confidentiality, as your name or that of your child is not

expected to feature in the study.

-----------------------------

Signature or thumbprint

(Patient or parent)

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