volume 2 - number 1/2011 - edizioni scripta manent planet · a cura dell’italian acne board,...

Volume 2 - Number 1/2011

This new issue of the European Journal of Acne is characterized by an importantnews: after just two issues, we got the ISSN certification: this represents a true record!

The primary objectives of next issues is to get, in 2012, the indexing of the journal on Embase: the achievement of this objective will represent the evidence that our journal isactually international. For instance, at least threeimportant clinical studies will be published in the next issues: all these studies have been carriedout or supervised by the Italian Acne Board and arebased on products or drugs that have been recently marketed in Italy, France and Spain.

In the next issue of the journal the abstracts of the Acne Day (Ferrara, September 16-17),organized by Professor Annarosa Virgili and Dr Enzo Bettoli, will be published.

Questo nuovo numero dello European Journalof Acne è caratterizzato da

un’importante novità: dopo appena duenumeri, siamo riusciti a ottenere la

certificazione ISSN: questo rappresentaun vero record!

Il principale obiettivo per i prossimi numeri è di ottenere, nel 2012, l’indicizzazione del giornale

su Embase: il raggiungimento di questo obiettivocostituirà la prova che la nostra rivista è veramente

internazionale. Per esempio, nei prossimi numerisaranno pubblicati almeno tre importanti studi clinici,

a cura dell’Italian Acne Board, relativi a prodotti e farmaci topici anti-acne

che sono stati recentemente introdotti sul mercato italiano, francese e spagnolo.

Nel prossimo numero saranno pubblicati gli abstract dell’Acne Day di Ferrara (16-17 settembre 2011), organizzato dalla Professoressa Annarosa Virgili

e dal Dr Enzo Bettoli.

Stefano VeraldiEditor

Volume 2, Number 1/2011

Registr. Tribunale di Milano n. 296 del 01/06/2011Scripta Manent s.n.c. Via Bassini, 41 - 20133 Milano

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Volume 2, Number 1/2011

ContentThe importance of monitoring quality of life in acneic patients pag 5Nevena Skroza, Ersilia Tolino, Giorgio La Viola, Sara Zuber, Ilaria Proietti, Concetta Potenza

Update your diagnostic skills pag 8Gerd Plewig

Acneiform eruption induced by testosterone pag 13Elena Guanziroli, Susanna Benardon, Mauro Barbareschi

Lupus miliaris disseminatus pag 17Daniele Gambini, Sergio Pericotti, Paolo Sena, Lorenzo Marchesi

Acne aestivalis or recurring actinic folliculitis? pag 21Mario Maniscalco, Francesco Bruno, Leonardo Zichichi, Laura Maniscalco

Acne fulminans: a case report pag 25Alessandra Mambrin, Raffaella Anfuso, Lidia Francesconi, Maria Rita Nasca, Giuseppe Micali

Editorial StaffDirettore Responsabile: Pietro Cazzola Consulenza grafica: Piero Merlini

Direttore Generale: Armando Mazzù Impaginazione: Stefania Cacciaglia

Italian Acne ClubMario Bellosta (Pavia), Carlo Bertana (Roma), Alessandro Borghi (Ferrara), Francesco Bruno (Palermo), Maria Pia De Padova (Bologna),

Paolo Fabbri (Firenze), Carlo Pelfini (Pavia), Mauro Picardo (Roma), Maria Concetta Potenza (Roma), Alfredo Rossi (Roma),Patrizio Sedona (Venezia), Aurora Tedeschi (Catania), Antonella Tosti (Bologna/Miami), Matteo Tretti Clementoni (Milano)

Editorial Board

EditorStefano Veraldi Milano

Co-EditorMauro Barbareschi Milano

Scientific BoardVincenzo Bettoli FerraraStefano Calvieri Roma

Gabriella Fabbrocini NapoliGiuseppe Micali Catania

Giuseppe Monfrecola NapoliNevena Skroza Roma

Annarosa Virgili Ferrara

Managing EditorAntonio Di Maio Milano

5

Introduction

Acne is a chronic inflammatory skin dis-ease involving the pilo-sebaceous unit 1. Its preva-lence is about 79-95% during puberty, progressive-ly decreasing to 3% observed in adults aged 35 to 44years 2. The various clinical aspects that we observein acne are related to its different pathogenetic fac-tors and to the time of evaluation; therefore acneiclesions can be defined as either non-inflammatory -open and closed comedones - or inflammatory -papules, pustules, nodules and cysts 3. Scars areconsequence of severe forms of acne. Since face is involved in 99% of cases, acne candeeply affect the different moments of a patientlife, i.e. conditioning its work and its social rela-tions. Psychological distress is exacerbated inteenagers, who tend to over-extimate and refusetheir condition 4-6.Jowett, et al. reported that 70% of patients withacne experiences feelings of embarrassment, 63%of anxiety and 27% of depression 7.If compared to people affected by other der-

matoses, acneic patients refer functional and emo-tional discomfort similar to those reported bypatients with psoriasis, that is traditionally consid-ered as a really disabling condition 8. Hence it isimportant to evaluate the implications that even themildest forms of acne can have on patients’ psy-chological balance.The aim of this study was to determine the relation-ship between quality of life and clinical severity inacneic patients before, during and at the end ofspecifical treatment.

Patients and Methods

We enrolled 330 patients with mild-to-severe acne, divided into two groups: the firstgroup consisted of 203 patients (52 M, 151 F, meanage 20.72) affected by mild acne treated with topi-cal therapy; the 127 patients (61 M, 66 F, mean age19,50) from the second group showed moderate or

European Journal of Acne and Related Diseases

Volume 2, n. 1, 2011

The importance of monitoring quality of lifein acneic patients

Nevena Skroza, Ersilia Tolino, Giorgio La Viola, Sara Zuber, Ilaria Proietti, Concetta Potenza Department of Dermatology “Daniele Innocenzi”- I Faculty of Medicine and Surgery - Polo Pontino, Sapienza University of Rome, Italy

SUMMARYAcne, as other dermatoses affect-ing exposed areas, can deeplyaffect patients’ social life. The aimof this study was to determine the

correlation between the severity of acne and the impactof the disease on patients’ life before, during and aftertreatment.We considered a total of 330 patients divided in twogroups; the !rst group included 203 patients with mildacne, treated with topical therapy, while the secondone included 127 patients affected by moderate orsevere acne, treated with systemic antibiotics orretinoids. The duration of the study was 90 days.

The severity of acne was calculated using the GlobalAcne Grading System (GAGS), while quality of lifewas determined by the Acne Quality of Life question-naire (Acne-QoL).We observed, as expected, a progressive improving inquality of life values as a consequence of clinicalimprovement of acneic lesions; but we also observedthat quality of life was similarly impaired in patientsfrom both groups, since even mild forms of acne heavi-ly in"uence psychosocial wellbeing. That is why, whenapproaching acneic patients, it is important to evaluatetheir condition in toto, in order to choose the correcttreatment.

Key words: Acne, Acne-QoL, GAGS, dermatology quality of life.

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severe acne treated with systemic antibiotics andretinoids, following the well-known therapeuticalgorithm (Table 1) 9. The duration of treatmentwas 90 days. The severity of acne was clinically evaluatedthrough the Global Acne Grading System (GAGS),while quality of life was examined using the Acne-QoL questionnaire (Acne-QoL) 10, 11. The GAGSform was filled in by the dermatologist during thefirst visit, and then on each subsequent control (on

4th, 8th and 12th week), while the Acne-QoL ques-tionnaire was filled in by the patient during the firstand on every subsequent visit.The evaluation of the differences in the two para-meters considered (GAGS and Acne-QoL) beforeand after treatment, and the statistical significanceof the study were calculated by the Wilcoxon test(non Parametric test for matched data), for theabsence of a normal distribution of the parameters.For the mean values ± standard deviation of thetwo-sample independent-groups, the T-test wasused. Mean differences were considered to be sig-nificant when p < 0.05.All statistical analyses were conducted using STATAstatistical software (STATA corporation, STATA Sta-tistical Software. Release 8.0, College Station, TX).

Results

At the end of the study, all the 330patients enrolled completed the treatment. Theaverage GAGS score of patients from the first


Volume 2, n. 1, 2011

Table 1.Distribution of sample related to treatment

Variables Topical Therapyn (S.D)

Systemic Therapyn (S.D)

Total Obs 203 127

Sex

Male 52 (0.44) 61 (0.50)

Female 151 (0.44) 66 (0.50)

Age (years)

Mean 20.72 (6.59) 19.50 (5.60)

Range 12-46 (6.59) 12-41 (5.60)

Figure 1. GAGS trend in topical and systemictherapy groups.

Figure 2. Acne-QoL index values in topicaland systemic therapy groups.

Figure 3. Mean Acne-QoL index values in malesand females of topical therapy group.

Figure 4. Mean Acne-QoL index values in malesand females of systemic therapy group.

7

group was about 16 at baseline, decreasing to avalue of 4 at the end of the topical treatment; a sim-ilar trend was observed in the second group, with areduction of the initial value of 27 to 15 at the endof the systemic therapy (Figure 1).Average Acne-QoL values at baseline of 73,36 inthe first and 68,61 in the second group improved to95,21 and 86,68 respectively, after three months oftreatment (Figure 2).Results were statistically significant (p < 0.00001),corresponding to a real improvement in both GAGSand Acne-QoL values. We din’t find significant dif-ferences between female and male patients in eachscale (Figures 3-4).

Discussion

Skin is an interface between us and theouter world; therefore it is clear that diseases suchas psoriasis, atopic eczema and acne can seriouslyimpair patients’ self-esteem, self-confidence andsocial relationships. It is not easy to measure theimpact of acne on a patient’s quality of life, sinceeven mild forms of acne can be seen as really dis-figuring and embarassing by affected individuals,

with deep psychological impact on their lives.What we observed in this study was, first of all, thata correct evaluation of the severity of acne and con-sequent application of the therapeutic algorithmimproves both clinical manifestations and quality oflife, as confirmed by the reduction of GAGS and bythe increase of Acne-QoL values respectively.But, more interestingly, we observed that despite thedifferent severity of acne in the two groups, baselinepatients’ quality of life was impaired almost at thesame level; it is clear that acne itself can be experi-enced as a distressing condition, independently fromits severity. So it’s important to be aware of the emo-tional status of patients with acne in order to choosethe correct treatment and evaluate the response totherapy.Furthermore, patient satisfaction and quality of lifehave to be considered when testing efficacy of prod-ucts used to treat acne, as these factors may influ-ence treatment adherence and outcomes 12. Usingthe simple Acne-QoL assessment can help cliniciansto optimize therapy and detect those patients withmild acne who are psychologically distressed.In conclusion, acne treatment should always be per-sonalized and aimed to obtain a “state of completephysical, mental and social well-being” 13.


Volume 2, n. 1, 2011

References

1. Gollnick HP, Finlay AY, et al. Can we define acne as a chron-ic disease? If so, how and when? Am J Clin Dermatol 2008;9(5):279-84.

2. White GM, et al. Recent findings in the epidemiologic evi-dence, classification, and subtypes of acne vulgaris. J Am AcadDermatol 1998; 39(2):34-7

3. Pawin H, Beylot C, et al. Physiopathology of acne vulgaris:recent data, new understanding of the treatments. Eur JDermatol 2004;14:4-12.

4. Tan JK. Psychosocial impact of acne vulgaris: evaluating theevidence. Skin Therapy Lett 2004; 9(7):1-3, 9.

5. Loney T, Standage M, et al. Not just “skin deep”: psychosocialeffects of dermatological-related social anxiety in a sample ofacne patients J Health Psychol 2008; 13(1):47-54.

6. Aktan S, Ozmen E, et al. Anxiety, depression, and nature ofacne vulgaris in adolescents Int J Dermatol. 2000; 39(5):354-7.

7. Jowett S, Ryan T. Skin disease and handicap. An analysis ofthe impact of skin conditions. Soc Sci Med 1985; 20:425-429.

8. Barankin B, DeKoven J. Psychosocial effect of common skindiseases. Can Fam Physician. 2002 Apr; 48:712-6.

9. Thiboutot D, Gollnick H, et al. New insights into the manage-ment of acne: An update from the Global Alliance to ImproveOutcomes in Acne Group J Am Acad Dermatol 2009; 60(5Suppl) S1-S50.

10. Martin AR, Lookingbill DP, et al. Health-related quality of lifeamong patients with facial acne - assessment of a new acne-spe-cific questionnaire. Clin Exp Dermatol 2001 Jul; 26(5):380-5.

11. Doshi A, Zaheer A, et al. A comparison of current acne grad-ing systems and proposal of a novel system. InternationalJournal of Dermatology 1997; 36(6):416-418.

12. Dréno B. Assessing quality of life in patients with acne vul-garis: implications for treatment. Am J Clin Dermatol 2006;7(2):99-106.

13. Preamble to the Constitution of the World Health Orga-nization as adopted by the International Health Conference,New York, 19-22 June, 1946.


Volume 2, n. 1, 2011

All the members of Mediterranean Acne Board at the end of the meeting

Anew scienti!c Society called Mediterranean Acne Board was created on November 27th in Naples.

Colleagues, researchers and experts in the !eld of Acne from Mediterranean countries, such as Egypt, Greece, Morocco, met with the Italian Acne Board during a workshop and they had the opportunity to share their knowledge and expertise.On this occasion we have had the honour of listening to a presentation byProf. Gerd Plewig from Munich, which discussed many interesting case studies.Prof. Plewig is a mentor and dear friend of my self and of all of us.None of us would have been interested in acne if it hadn’t been for the contribution and research on sebaceous glands of Albert Kligman and GerdPlewig.It’s a great privilege to publish his interesting manuscript in our journal

Francesco Bruno

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Introduction

The first session of the Italian Acne Boardtook place on November 26-27, 2010, in Napleswith participants of several other countries. Themembers outlined a business plan and presentedchallenging case presentations. The efforts of ourItalian colleagues are to be congratulated. Theresults of this meeting and future ones will help usto better understand acne and its related disorders,thus transforming this knowledge into our dailypractises.

The overlap situation

It is not so rare that a patient presentssimultaneously two or more skin diseases of theacne family or its simulators. Or he has one variantof acne first, to be followed by other acne-like

looking dermatosis. Overlap dermatoses may makethe clinical diagnosis difficult as well as therapeu-tic strategies. Very little is published on these over-lap situations.Table 1 is but one list of these manifestations. Notonly two, but three or even more skin diseases canaffect teenagers and adults.


Volume 2, n. 1, 2011

Update your diagnostic skills

Gerd PlewigDepartment of Dermatology Ludwig-Maximilian-University Munich, Germany

SUMMARYIt is not so rare that a patient pre-sents simultaneously two or moreskin diseases of the acne family orits simulators. Overlap dermatoses

may make the clinical diagnosis dif!cult as well astherapeutic strategies. Atrophodermia vermiculata is

often not recognized and considered as scarring fromacne. Little is known about the etiology and pathogen-esis of this primarily non-in"ammatory genetic disor-der. Histopathological !ndings differ de!nitely fromthe ones seen in acne. Careful clinical inspection anda good history are essential.

Key words: Atrophodermia vermiculata.

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Table 1

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Atrophodermia vermiculata

This scarring disease is often not recog-nized and considered as scarring from acne, whichis not the case. Table 2 provides the synonyms.Figure 1 is a typical example of the worm-eatenshallow scarring of Atrophodermia vermiculata onthe cheeks of a young patient. The first compre-hensive description was given by the great derma-tologist in Hamburg, Paul Gersson Unna.

Details of his life and his immense contributions toour specialty can be read in the chapter on Unna inthe upcoming book Pantheon of Dermatology(Springer Verlag, Heidelberg, 2011) with manyclinical and histological illustrations. Table 3 is asummary of his observations published in the mag-nificent International Atlas of Rare Skin Diseases.Incidentally, Unna was the first to demonstrate theorganism associated with acne, today specified asPropionibacterium acnes. Thus he was also a greatresearcher in acne. Figures 2 and 3 are the originalclinical findings and histological drawings.


Volume 2, n. 1, 2011

Table 3

Table 2

Figure 1

Figure 2

Figure 3

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Little is known about the etiology and pathogene-sis of this primarily non-inflammatory genetic dis-order. Table 4 lists that both sexes are affected withfamilial occurrence. It remains to be seen if the pat-tern is autosomal dominant, and whether there is amosaic-like pattern.Several papers have presented histopathologicalfindings. These differ definitely from the ones seen inacne, if early stages are studied. The sebaceous andprobably terminal follicles (beard areas in males)undergo dystrophy. The follicles are of asymmetricalshape, their infundibular canal widened, filled with

keratinous debris, and are surrounded by perifollicu-lar sclerosis (Table 5, Figure 4).As the disease ranges from subtle to bizarre expres-sions, the histopathology varies considerably.

Diagnosis

Careful clinical inspection and a good his-tory are essential. Rarely one needs histopathology.

Therapy

Table 6 provides clues. Inform the patientwhat he has or what he does not have. Antibioticsor isotretinoin are indicated once there is substan-tial inflammation. Otherwise surgical proceduresmay help to improve the scarring.

Our Key Patient

The patient, in his late twenties, presentedto our acne clinic with “acne” on his face andtrunk. His history tells that he started with scars onhis face around puberty, mainly on the cheeks with-out any preceeding inflammation. Much later hedeveloped inflammatory lesions on the back andchest with comedones, papules, pustules, abscess-es, giant comedones and scars.

Diagnosis

The patient has an overlap of Atropho-


Volume 2, n. 1, 2011

Table 4

Table 5

Table 6

Figure 4Figure 4

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Literature

Plewig G. Akne. Internationale Neuigkeiten. In: Fortschritteder praktischen Dermatologie und Venerologie 2008, Bd 21(Ruzicka T, Wolff H, Thomas P, Prinz J, Hrsg), Springer,Berlin, 2008, S439-443.

Löser C, Plewig G, Burgdorf W. Pantheon of Dermatology. First


Volume 2, n. 1, 2011

dermia vermiculata (his initial disease) and acne conglobata (his over-lap disease).Although he had consulted many dermatologists and received variousacne treatments, the diagnosis of Atrophodermia vermiculata was neverprovided. Figures 5 and 6 depict the classical shallow scars on his face and behindthe ears. Figure 7 is the close-up view of his back with typical lesionsof acne conglobata.

Treatment

The patient opted for oral isotretinoin for his acne conglobata,from which he greatly benefited, and accepted the second diagnosis ofAtrophodermia vermiculata, but did not opt for surgical procedures toimprove the shallow scarring.

Figure 5

Figure 6 Figure 7

English edition. Springer, Heidelberg, 2011.

Unna PG. Ulerythema acneiforme. In: International Atlas ofRare Skin Diseases (Morris, Unna, Duhring, Leloir eds). Voss,Hamburg. Part II, plate 2. Delivered March 29, 1890.

13

Introduction

Hormonal medications that are androgenicin nature may cause acneiform eruptions by influ-encing sebaceous gland growth and sebum produc-tion 1.Examples include anabolic steroids, topical andsystemic testosterone, follitropin alfa and humanchorionic gonadotrophin 2-4.Testosterone is the most important male sex hor-mone and is crucial for male health and develop-ment. Approximately 6–10% of men, dependingon age, have low testosterone concentrations andsigns or symptoms of testosterone deficiency,including delayed puberty, erectile dysfunction,sleep disturbance, depression, lethargy and dimin-ished physical performance 5.These men benefit from testosterone replacement,which improves mood, energy and sense of well-being, increases bone and muscle mass and main-tains sexual function.Clinical studies have shown that testosteronereplacement is also a valid strategy in hypogo-nadotropic hypogonadism (HH) 6.

HH is defined by the absence of sex steroid synthe-sis associated with the lack of appropriategonadotrophin secretion. This leads to a variabledegree of impuberism, often diagnosed duringchildhood or adolescence 3.The safety profile of testosterone replacement ther-apy is characterized by a class effect that compriseskin reactions, including acneiform rash, hypertri-chosis, flushing and striae distensae 7, 8.We report here a male patient with HH, who devel-oped an acneiform eruption during treatment withsystemic testosterone.

Case report

A 17-year-old man was referred to ourDermatology department because of a recent onsetof an asymptomatic dermatitis. His medical historyincluded orchidopexy for bilateral cryptorchidismand delayed puberty.Based on hormonal function tests and testicular


Volume 2, n. 1, 2011

Acneiform eruption induced by testosterone

Elena Guanziroli, Susanna Benardon, Mauro BarbareschiDepartment of Anesthesiology, Intensive Care and Dermatology Sciences, University of Milan, I.R.C.C.S. Foundation Ca' Granda,Ospedale Maggiore Policlinico, Milan, Italy

SUMMARYSystemic testosterone has some dermatological side effects asacneiform rash, !ushing, striaedistensae, hypertrichosis and other

signs of virilization.Acneiform eruptions start from the follicles and theprimary lesion is always follicular in!ammation.Comedones are generally fewer in number and

secondary in respect acne vulgaris.We report a male patient with hypogonadotropichypogonadism that developed diffuse acneiformeruption after treatment with injectable testosterone.The treatment of these cases is long lasting because ofadministration of testosterone cannot be suspended.For this reason, low doses of systemic isotretinoin maybe a therapeutic option.

Key words: Acneiform eruption, testosterone.

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ultrasound, endocrinologists made diagnosis ofHH and started injectable testosterone enanthatereplacement therapy (125 mg every two weeks).After a short period of treatment, a lot of papulesand pustules were noted on the face, trunk, armsand back. The patient was otherwise healthy.Before testosterone therapy he did not sufferedfrom acne and his family history was negative foracne vulgaris. Physical examination revealed inflammatorymonomorphic lesions, while comedones and scarswere absent. Clinical features and anamnestic datawere consistent with a diagnosis of testosterone-induced acneiform eruption. Due to the extensive skin involvement and the needto continue the intake of the drug, low-dose oralisotretinoin (0,2 mg/kg/day) was started.After two months of treatment we noted animprovement in the clinical picture with a reduc-tion of the inflammatory lesions (Figures 1-4). Thepatient was satisfied and did not have side effects.

Discussion

Testosterone is the gold standard therapyfor hypogonadism, excessive tall stature, azoosper-mia and andropause. It is a steroid hormone withactions in a wide variety of organs and tissues. The major side effects involve cardiovascular sys-tem, liver, prostate and skin and are dose-relateddependent on the daily dosage, the duration of thetreatment and the total cumulative dosage 3.Acneiform eruption is the earliest and most charac-teristic skin side effect after topical and systemictestosterone. It usually appear suddenly (withindays or hours in some cases) and is monomor-phous, with follicular papules and pustules.Initially, comedones are lacking but they may bedeveloped secondary to follicular inflammation.Scars are absent. The most common sites ofinvolvement are face, chest, back and arms 9.The pathogenesis of testosterone-induced acneiformeruptions takes place at the level of the piloseba-ceous follicle. The most relevant factor is 5a-dihy-drotestosterone, the testosterone active metabolite,which causes hypertrophy of the sebaceous glands

with a consequent overproduction of sebum 10, 11.Sebum acts as a nutrition source for bacteria of thenormal skin commensal flora, which grow andmultiply in the retained sebum releasing pro-inflammatory citokines. These alert and attractwhite cells from the blood, and that’s what leads toinflammation 12.There is probably a wide spectrum of sensitivity ofthe pilosebaceous apparatus after exposure to vary-ing levels of androgens that may help to explainwhy only a minority of men treated with testos-terone develop acneiform eruptions. A list of drugsinducing acneiform eruptions is listed in table 1.

Stopping the trigger is the most important strategyof treatment. When it is impossible, treatment most-ly involves conventional topical medications usedfor acne vulgaris, such as antibiotics and retinoids 9.Oral tetracyclines may be useful for their anti-inflammatory and immunomodulatory properties 13.Isotretinoin causes suppression of size and activityof sebaceous glands and also has anti-inflammato-ry effects 14.In our case, the need to continue the treatment fora long time, the impossibility of stopping testos-terone medication and the extensive skin involve-ment led us to treat the patient with low doses ofisotretinoin. The treatment proved effective andwithout side effects.


Volume 2, n. 1, 2011

Table 1. Drugs involved in acneiform eruptions.

Steroids (topical-systemic)

Testosterone

Vitamins B1, B6, B12, D

Antidepressants (lithiun-amineptine)

Antiepileptics (Valproic acid)

Doxycycline, minocycline

Isoniazid

Puva

Thiroid preparation (Thiouracil)

Disulfiram

Chloroquine

Azathioprine

Halogens (bromides-Iodines, Kelp diet)

EGFR inibitors

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Volume 2, n. 1, 2011

Figures 1-4.Clinical aspect before and after treatment.

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Volume 2, n. 1, 2011

short review. Acta Dermatovenerol Alp Panonica Adriat 2007;16:117-22.8. Hernández-Núñez A, Daudén E, García-F-Villalta MJ, Ríos-Buceta L, García-Díez A. Hirsutism secondary to topical testos-terone: report of two cases and review of the literature. J EurAcad Dermatol Venereol 2004; 18:208-10.9. Burgdorf WHC, Plewig G, Wolff HH, Landthaler M. Braun-Falco´s Dermatology. Heidelberg: Springer Medizin Verlag; 2009.10. Kurokawa I, Danby FW, Ju Q, Wang X, Xiang LF, Xia L,Chen W, Nagy I, Picardo M, Suh DH, Ganceviciene R, SchagenS, Tsatsou F, Zouboulis CC. New developments in our under-standing of acne pathogenesis and treatment. Exp Dermatol2009; 18:821-32. 11. Zouboulis CC, Eady A, Philpott M, Goldsmith LA, OrfanosC, Cunliffe WC, Rosenfield R. What is the pathogenesis ofacne? Exp Dermatol 2005; 14:143-52.12. Jeremy AH, Holland DB, Roberts SG, Thomson KF,Cunliffe WJ. Inflammatory events are involved in acne lesioninitiation. J Invest Dermatol 2003; 121:20-7.13. Sapadin AN, Fleischmajer R. Tetracyclines: nonantibioticproperties and their clinical implications. J Am Acad Dermatol2006; 54:258-65. 14. Layton A. The use of isotretinoin in acne. Dermatoendocrinol2009; 1:162-9.

References

1.Thiboutot D. Acne: hormonal concepts and therapy. ClinDermatol 2004; 22:419-28.

2. Matsumoto AM, Snyder PJ, Bhasin S, Martin K, Weber T,Winters S, Spratt D, Brentzel J, O'Dea L. Stimulation of sper-matogenesis with recombinant human follicle-stimulating hor-mone (follitropin alfa; GONAL-f): long-term treatment inazoospermic men with hypogonadotropic hypogonadism. FertilSteril 2009; 92:979-90.

3. Rhoden EL, Morgentaler A. Risks of testosterone-replace-ment therapy and recommendations for monitoring. N Engl JMed 2004; 350:482-92.

4. Yu YM, Punyasavatsu N, Elder D, D'Ercole AJ. Sexual devel-opment in a two-year-old boy induced by topical exposure totestosterone. Pediatrics 1999; 104:e23.

5. Araujo AB, Esche GR, Kupelian V, O’Donnell AB, TravisonTG, Williams RE, Clark RV & McKinlay JB. Prevalence ofsymptomatic androgen deficiency in men. J Clin EndocrinolMetab 2007; 92:4241-47.

6. Snyder PJ, Peachey H, Berlin JA, Hannoush P, Haddad G,Dlewati A et al. Effects of testosterone replacement in hypogo-nadal men. J Clin Endocrinol Metab 2000; 85:2670-77.

7. Wollina U, Pabst F, Schönlebe J, Abdel-Naser MB, Konrad H,Gruner M, Haroske G, Klemm E, Schreiber G. Side-effects oftopical androgenic and anabolic substances and steroids. A

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Introduction

Lupus miliaris disseminatus faciei (LMDF)is a rare dermatological disease, frequently occur-ring in adolescent and young adults of both sexes.It is clinically characterized by the presence ofsmall, discrete, red-brown, dome-shaped papulesmainly affecting the central area of the face, whileextrafacial localization is uncommonly observed.The onset is generally fairly rapid, eruptive, withmultiple lesions in crops. The disease runs a chron-ic course persisting for months to years in spite ofthe therapies and usually involutes spontaneouslyleaving typical small pitted scars 1. Histopathologyshows caseating and non caseating epithelioid cellgranulomas in the superficial and deep dermis,mixed with numerous lymphocytes and rare multi-nucleate giant cells 2.

Case report

A 29-year-old man presented with asymp-tomatic eruptive red-brown, dome-shaped papulesand small nodules on the face (Figure 1). The lesionsappeared rapidly 4 months before, were diagnosedas folliculitis and unsuccessfully treated with doxi-cycline 100 mg/die for several weeks. At the time ofour observation the papules and small nodules weredistributed mainly in the central area of the face,especially involving the forehead (Figure 2), superi-or lip area (Figure 3) and lower eyelids. The patientwas in otherwise good health condition, had no othercutaneous lesions, denied application of topicalsteroid and had no family history of similar erup-tions. Rosaceiform aspects such as erythema, angec-tasias and flushing were absent. A biopsy specimenrevealed superficial and deep dermal epithelioid cell


Volume 2, n. 1, 2011

Lupus miliaris disseminatus

Daniele Gambini, Sergio Pericotti*, Paolo Sena, Lorenzo MarchesiUniversità degli Studi di Milano, A.O. Ospedali Riuniti di Bergamo, USC Dermatologia, USC Anatomia Patologica*, Bergamo, Italy

SUMMARYLupus miliaris disseminatus faciei(LMDF) is a rare dermatologicaldisease, clinically characterized bythe presence of small, discrete, red-

brown, dome-shaped papules mainly affecting the centralarea of the face, while extrafacial localization is uncom-monly observed. A 29-year-old man presented with papules and smallnodules of the face, especially involving the forehead,superior lip area and lower eyelids. A skin biopsyrevealed superficial and deep dermal epithelioid cellgranulomas with central caseating necrosis areas, sur-rounded by lymphocyte infiltrate and rare multinucleategiant cells. A chest X-ray, routine laboratory exams and

Mantoux test were negative. A diagnosis of LMDF wasmade. After 6 weeks of minocycline some lesionsimproved, but new ones appeared with a single papule onthe dorsal right hand. We confirmed our diagnosis of“lupus miliaris disseminatus”, removing the genitive“faciei” in order to be more precise. The disease healedabout 18 months after presentation. Actually LMDF is regarded as a separate and distinctiveentity, with some rosacea-like features, and not a granu-lomatous form of rosacea. In recent years there was aproposal to switch the name of the disease from LMDFto the acronym FIGURE (Facial Idiopathic GranUlomaswith Regressive Evolution) but, to date, this nomencla-ture change has not widely accepted.

Key words: Lupus miliaris disseminatus faciei, FIGURE, granulomatous rosacea, tuberculid.

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Volume 2, n. 1, 2011

Figure 1. Eruptive papulesand small nodule on thefaceFigure 2. A closer imageof the foreheadFigure 3. Grouped papulesof the superior lip areaFigure 4. Superficial anddeep dermal epithelioidcell granulomas withcentral caseating necrosisareas (hematoxylin-eosinstain 10 x)

Figure 5. A highermagnification of theepithelioid cell granulomas(hematoxylin-eosinstain 50 x)

Figure 6. A singlered-brown papuleon the dorsal right hand

Figure 1

Figure 5Figure 4

Figure 3

Figure 2

Figure 6

19

granulomas with central caseating necrosis areas(Figures 4-5), surrounded by conspicuous lympho-cyte infiltrate and rare multinucleate giant cells. Achest X-ray, routine laboratory exams and Mantouxtest were negative.A diagnosis of LMDF was made and oral minocy-cline (100 mg/die) was started. After 6 weeks somelesions markedly improved, but new papules andsmall nodules appeared on the face, together with asingle red-brown papule on the dorsal right hand(Figure 6). A skin biopsy of this lesion was per-formed and histopathology was similar to the firstbiopsy, but with minor surrounding lymphocytes.We confirmed our diagnosis of “lupus miliaris dis-seminatus”, removing the genitive “faciei” becauseof the presence of the papule on the hand and decid-ed to stop therapies. In the following months lesionsbecame less apparent, subsequently fading awayand completely healing about 18 months after pre-sentation. Only some of the papules healed withsome athrophic pitted scars.

Discussion

LMDF was described in 1903 as a faceeruption of discrete dull red-brown papules withspontaneous involution over several weeks, leav-ing pigmented scars 3. LMDF was originally con-sidered to be a variant of lupus vulgaris or a tuber-culid, but actually there are many data against thissuggested link: variable, often negative, cutaneoushypersensitivity to tuberculin; absence of bothconcomitant tubercolosis and bacilli in skinlesions; inefficacy of antitubercular therapy in thevast majority of patients; failure of molecular biol-ogy techniques to demonstrate Mycobacteriumtubercolosis DNA in cutaneous lesions 4.The pathogenesis of LMDF remains controversial.Some Authors consider LMDF a granulomatousform of rosacea 5, because the granulomas often ap-pear in association with the pilosebaceous units 6, 7

and epithelioid granulomas have been found in somepatients with rosacea. However, from a clinical pointof view, there are many differences between rosaceaand LMDF: predominance in young adults and ado-lescents; involvement of facial areas frequently

spared by rosacea, such as lower eyelid and superiorlip; no clinical worsening after alcohol and spicyfood intake or exposure to sunlight; absence of ery-thema, flushing and teleangectasias; inefficacy ofdrugs; self-limited course with scarring.Histologically, dermal epithelioid cell granulomasare observed in both diseases, but caseation necro-sis is only rarely observed in granuolmatousrosacea. Because of all these differences, LMDFshould probably better be considered a separateand distinctive rosacea-like entity and not a granu-lomatous form of rosacea 8. Granulomatousrosacea and sarcoidosis could represent each endof the same disease spectrum and LMDF could bepart of this spectrum 8. Although there have beenmany suggestions about the pathogenesis ofLMDF, it remains unknown.Clinically, LMDF occurs most commonly on themedial and lateral areas of the face and sometimesextends onto the neck and chin. Extrafacialinvolvement is only occasionally observed, butprobably is more common than reported 8, affect-ing mostly axillae, shoulders, arms, hands, groins,legs and genitalia 9. Reports of extrafacial LMDFwithout facial involvement are extremely rare, andwe found only two described patients in the litera-ture, in which eruption occurred exclusively in theaxilla 10 and the neck and the chest 11 respectively.In our case the clinical presentation was typicaland only during follow-up an extrafacial localisa-tion on the dorsum of right hand appeared. For thisreason we changed our diagnosis from LMDF to“lupus miliaris disseminatus”, removing the geni-tive “faciei” in order to be more precise. LMDF has been referred with numerous otherterms in the past: Lewandowsky’s ”milia-likerosaceiform tuberculids” 12, micropapular tuber-culid 13, lupoid rosacea 14, Barthèlemy’s “acnitis”15 and acne agminata 16. LMDF is the most com-monly used and accepted term in the literature,even if the word “lupus” is confusing and the word“faciei” is not always correct because of extrafa-cial localisation. Thus, in 2000, Skowron andFrench colleagues proposed a change to theacronym FIGURE (Facial Idiopathic GranUlomaswith Regressive Evolution) 17; to date, this newname does not seem to be widely accepted 18. It


Volume 2, n. 1, 2011

20

avoids the link to acne or tubercolosis, but should benot considered a “perfect” term because the “F” let-ter seems to limit the disease to facial areas, not con-sidering extrafacial lesions. The therapy of LMDF is generally unsatisfactory.Moreover the course of the disease, with sponta-neous involution after numerous months, couldbias the effects of therapies. Anyway tetracyclines,glucocorticoids, antitubercular medications, anti-malarial drugs, dapsone and isotretinoin have been

found to be effective in some patients, even if con-trolled studies are lacking 18. In particular, tetracy-clines are generally considered first-line treat-ment 18, whereas dapsone has been shown to pre-vent new lesions and shorten the duration of the dis-ease 19. Systemic low-dose steroid therapy for somemonths could be useful also in scarring preventionespecially if used soon after the onset of disease 20,while isotretinoin demonstrated effectiveness insporadic LMDF cases 21.


Volume 2, n. 1, 2011

References

1. Tappeiner G, Wolff K. Tubercolosis and other mycobacterialinfections. In: IM Freedberg et al. (eds), Fitzpatrick’s dermatol-ogy in general medicine, 6th edition, New York, The Mac Graw-Hill Companies, Inc; 2003; 1944.

2. Mullanax MG, Kierland R. Granulomatous rosacea. ArchDermatol 1970; 101:206-11.

3. Radcliffe-Crocker H: Disease of the Skin, ed 3. London,Lewis, 1903.

4. Hodak E, Trattner A, Feuerman H, Feinmesser M, Tsvieli R,Mitrani-Rosembaum S, David M. Lupus miliaris disseminatusfaciei – The DNA of Mycobacterium tubercolosis is notdetectable in active lesions by polimerase chain reaction. Br JDermatol 1997; 137:614-9.

5. Helm KF, Menz J, Gibson LE, Dicken CH. A clinical andhistopathological study of granulomatous rosacea. J Am AcadDermatol 1991; 25:1038-43.

6. Shitara A. Clinicopathological and immunological studies oflupus miliaris disseminatus faciei. J Dermatol 1982; 9: 383-95.

7. El Darouti M, Zaher H. Lupus miliaris disseminatus faciei -pathological study of early, fully developed and late lesions. IntJ dermatol 1993; 32: 508-11.

8. van de Scheur MR, van der Waal RIF, Starink TM. Lupusmiliaris disseminatus faciei: a distinctive rosacea-like syndromeand not a granulomatous form of rosacea. Dermatology 2003;206(2): 120-3.

9. Moreira E, Lisboa C, Azevedo F. Lupus Miliaris DisseminatusFaciei - a case with preferential involvement of the penis. TrabSoc Dermatol Venereol 2008; 66 (3): 453-6.

10. Bedlow AJ, Otter M, Marsden RA. Axillary acne agminata

(lupus miliaris disseminatus faciei). Clin Exp Dermatol 1998;23-125-8.

11. Dae Suk K, Kiu Yeop L, Yung US, Mi Riung R, Min Geol L.Lupus miliaris disseminatus faciei without facial involvement.2008; 88(5):504-5.

12. Lewandowsky F. Uber Rosacea-ahnliche Tuberkulide desGesitches. Corr Bl Schweiz Artze 1917; 47:1280-2.

13. Laymon CW, Michelson HE. The micropapular tuberculid.Arch Dermatol Syphilol 1940; 42:625-40.

14. Michelson HE. Does the rosacea-like tuberculid ofLewandowsky exist? Arch Dermatol 1958; 78:681-8.

15. Saint-André P, Chastel F, Biot J. Barthélémy’s acnitis. BullSoc Fr Dermatol Syphiligr 1970; 77(2):221-2.

16. Scott KW, Calnan CD. Acne agminata. Trans St John’sHosp Dermatol Soc 1967; 50:60-9.

17. Skowron F, Causeret AS, Pabion C, et al.: FIGURE: facialidiopathic granulomas with regressive evolution. Is Lupus mil-iaris disseminatus faciei still an acceptable diagnosis in the thirdmillennium? Dermatology 2000; 201(4): 287-9.

18. Esteves T, Faria A, Alves R, Marote J, Viana I, Vale E.Lupus Miliaris Disseminatus Faciei: a case report. DermatologyOnline Journal 2010; 16(5):10.

19. Kumano K, Tani M, Murata Y. Dapsone in the treatment ofmiliary lupus of the face. Br J Dermatol 1983; 109:57-62.

20. Uesugi Y, Aiba S, Usaba M, Tagami H. Oral prednisone in thetreatment of acne agminata. Br J Dermatol 1996; 134:1098-1100.

21. Bahadir S, Apaydin R, Cimsit G.. Oral isotretinoin therapyin two patients with lupus miliaris disseminatus faciei. JDermatol Treatment 1999; 10:205-8.

21

Case report

In the period from May 2009 to August2010, we saw 14 patients (9 women-5 men), affect-ed with Acne aestivalis 1-3. The patients’ average agewas in the range of between 17 and 27. The lesionssprang up suddenly, after 12-72 hours of sun expo-sure. There was a typical monomorphismus: follic-ular papules with a size of 1-2 mm and an absenceof pustules and comedones. The mainly affectedareas were the back, neck and arms (Figures 1-7).

Only five patients complained of light itching andthere were no sleep disturbances. The otherpatients had no symptoms of itching or burning.Eight of our patients had been affected for the firsttime, the other six had been having relapses everysummer for a few years.The histology after punch biopsies performed ontwo different patients showed an infiltration oflymphocytes in the reticular dermis, exocytosis of


Volume 2, n. 1, 2011

Acne aestivalis or recurring actinic folliculitis?A new term to define acne aestivalis

Mario Maniscalco1, Francesco Bruno2, Leonardo Zichichi3, Laura Maniscalco1

1Dermatologist, Sciacca, Italy 2Dermatologist, Milan/Palermo, Italy3Dermatologist, Trapani, Italy

SUMMARYAcne aestivalis or Mallorca Acnewas described for the first time in1972 by Hjorth and Sjølin in agroup of Scandinavian tourists

who showed a cutaneous eruption after a few hours ofsun exposure during a summer vacation in BalearicIslands. Small follicular, non-itching papules arose onpeculiar areas (upper part of chest, arms, forearms and

neck, the face is rarely or never involved). The majorityof the patients were women aged between 20 and 30.There were no comedones in the lesions.The typical treatment for acne was unsuccessful.The eruption disappeared spontaneously in a fewmonths. We present our clinical and therapeuticalexperience based on a group of 14 patients with acneaestivalis.

Key words: Acne aestivalis, sunscreen, monomorphismus, actinic folliculitis.

Mar

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Figure 1 Figure 2

22

neutrophils in the epidermis, with a dense perivas-cular lymphocyte infiltration 4 (Figures 8-11).The microbiological investigation excluded thepresence of bacteria in the lesions.In the blood examination, cbs, liver, and kidneyfunctions were normal.Patch and photopatch tests for sunscreen were nega-tive, although only four patients had used sunscreenand ten hadn’t used any from of sun protection5.Ten of our patients were receiving a topical treat-ment of retinaldheyde 0.1% and glycolic acid 6 %.The therapy was administered every evening for 3weeks, then every other day for 2 weeks. We rec-ommended the discontinuation of any UV screenor protection and avoiding exposure to sunlightfrom 11 a.m. to 3 p.m.The other four patients had to use a placebo creamwith the same form of application.After 5 weeks of treatment with retinaldehyde

0.1%, 4 patients showed a slight improvement inthe clinical feature (reduction of numbers ofpapules), 3 other patients showed excellent results(no more papules). Only three of them did notshow any improvement. No patients showed any


Volume 2, n. 1, 2011

Figure 3

Figure 5

Figure 4

Figure 6

Figure 7

23

side effects or adverse reactions, except for 2patients who complained of itching during the firsttwo days of treatment. However, the itching wasnot severe enough to warrant the discontinuationof the treatment. Among patients in the “placebogroup”, only one showed signs of improvement,but the other 4 did not show changes in the clinicalfeature.

Discussion

Even today, acne aestivalis doesn’treceive nearly as much attention as it should.Perhaps this is because it is not well-known orstudied enough. In fact, publications on this sub-ject are few and many of them are outdated.In 1998, Plewig and Jansen classified acne aesti-valis, iatrogenic acne, gram negative folliculitis,and necrotic acne into a group of acneiform der-matoses with the typical hallmarks such as follicu-lar eruptions similar to that of Acne vulgaris.

However, the eruptions differed a little due to theirsudden onset, the unusual affected areas, themonomorphismus (same stage of development),the near absence of comedones, and the ensuingacne age6.In 1998, Labandeira and colleagues, described theessential features of Actinic Superficial Folliculitisin a paper and concluded with the followinghypothesis: acne aestivalis and recurring folliculitisof infundibulum are actually different aspects ofonly one clinical feature. Actinic folliculitiesunderlines the pathogenetic role of exogen factorssuch as a warm-humid environment, seborrhea,hyperhidrosis, sunscreen use, and especially sunand/or UVA exposure7.The biggest contributing factor in the pathogenesisof acne aestivalis is most certainly sun exposure.All patients, who were young and mostly women,had had sun exposure for a few hours before theonset of the lesions. However, some of them experienced a relapse ofthe dermatosis after every occasion of sun expo-


Volume 2, n. 1, 2011

Figure 8 Figure 9

Figure 12. Patient after UVA shower.

Figures 8-9.First biopsy.Necrosis of super!cial dermis, neutrophils and histiocytes,perivascular neutrophil in!ltrate.

Figures 10-11.Second biopsy.Lymphocytic in!ltrate in reticular dermis, exocytosisof neutrophils in the epidermis with a dense perivascularlymphocyte in!ltrate.

Figure 10 Figure 11

24

in polymorphous light eruption. J Dermatolog Treat, 2001;12(1):3-8.6. Plewig G, Jansen T. Acneiform dermatoses. Dermatology,1998; 196(1):102-7.7. Verbof J. Actinic folliculitis. Br J Dermatol, 1985; 113(5):630-1.8. Cunliffe WJ, Gollnick HPM. ACNE diagnosi e terapia,Martin Dunitz editor, 2001.9. Bruno F, Di Pietro A, Micali G, Innocenzi D, Bettoli V, DragoF, Baldari M. Sterile Follicular-Pustular (Acneiform) RashDuring Therapy With Inhibitors Of Epidermal Grow FactorReceptor (EGFR) A New Clinical Feature. J Plastic Dermatol,2007; 3(1):51-54.

References

1. Hjorth N, Sjolin KE, Sylvest B, Thomsen K. Acne aestivalis--Mallorca acne. Acta Derm Venereol, 1972; 52(1):61-3.

2 Mills OH, Kligman AM. Acne aestivalis. Arch Dermatol,1975; 111(7):891-2.

3. Petruzzellis V, Scardigno A, Velon A. Acne aestivalis. G ItalDermatol Venereol 1986; 121(1):55-60.

4. Sjølin KE. Acne aestivalis. A histopathological study. ActaDerm Venereol Suppl (Stockh) 1979; 59(85):171-6.

5. Rippke F, Wendt G, Bohnsack K, Dörschner A, Stäb F,Hölzle E, Moll I. Results of photoprovocation and field stud-ies on the efficacy of a novel topically applied antioxidant


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sure. Furthermore, cases of cutaneous eruptionssimilar to acne aestivalis have been described afterUVA shower ex position. UVA would transformcutaneous squalene into squalene peroxide with anobstructive effect8.We had a patient in our group with a cutaneouseruption similar to acne aestivalis, (but more simi-lar to erythematosus), which arose after a UVAshower (Figure 12).The results of our study do not confirm any patho-genetic role of suncreen. The treatment with topi-cal retinaldehyde 0.1% and glycolic acid 6% waseffective and well tolerated in most patients.We believe that further photobiological, microbio-logical, and therapeutic studies are necessary for adeeper under standing of the yet unknown aspectsof such dermatosis. It’s also important to better

identify the relationship between acne aestivalis,other follicular eruptions (such as superficialactinic folliculitis, recurring infundibulum-folli-culitis), and acneiform dermatoses.As a consequence of the evidence mentioned so far,we advise changing the term Acne Aestivalis or“Mallorca Acne”. Both terms are limiting becausethey only carry a historical and suggestive mean-ing. The new term we suggest is: “RecurringActinic Papulosis.” The word “Acne” should “disappear” due to theabsence of comedones in the clinical feature.On the other hand, would we ever call the folliculareruptions during the therapy with the inhibitors ofEGFR (Epidermal Grow Factor Receptor) acne? 9

This way, it would be easier to distinguish this fea-ture from the other acneiform eruptions.

25

Introduction

“Acne fulminans” is a rare and severe con-dition associated with systemic symptoms andabnormal laboratory findings1. Plewig and Kligmancoined this term in 1975, remarking the characteris-tic sudden onset and severity of the disease2. It pre-dominantly affects Caucasian male adolescents witha history of mild to moderate acne.Its pathogenesis is still unclear, and its treatment isoften troublesome. We report a case of acne fulmi-nans in a 17-year-old boy that recently come underour observation.

Case report

A 17-year-old Caucasian boy presented inJune 2009 with an acute papulo-pustular eruptionon his back, chest and face. The patient had 2-yearhistory of untreated mild acne.At physical examination hundreds of red papulesand pustules covered by superficial, thick, yellowadherent crusts were present on the back.Nodules and plaques (Figure 1a-b) evolving intosuppurative ragged hemorrhagic ulcerations werealso evident3.Multiple, sometimes confluent papules and pus-


Volume 2, n. 1, 2011

Acne fulminans: a case report

Alessandra Mambrin, Raffaella Anfuso, Lidia Francesconi, Maria Rita Nasca,Giuseppe MicaliDermatology Clinic, University of Catania, Italy

SUMMARYAcne fulminans (AF) is a rare con-dition of unknown cause, charac-terized by a sudden onset, usually

associated with systemic features and laboratory abnor-malities. We report a case of AF that was successfullytreated with oral isotretinoin and oral prednisone.

Key words: Acne fulminans, isotretinoin, prednisone.

Ales

sand

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Figure 1a-b.Red papules and pustules covered by superficial, thick, yellow adherent crusts on the back.

Nodules and plaques are also evident.

1a 1b

26

tules, were also observed on the chest and face(Figure 2a-b-c).The patient had been febrile (37.2 °C) in the lastweek, but he did not report arthralgias or musclepain. Laboratory investigations revealed raised ery-throcyte sedimentation rate (ESR) (1° hour: 57; 2°hour: 112; N: 0-10; Katz index: 56.50; N: ! 15),antistreptolysin-O titer (ASO) (368; N: 0-200), C-Reactive protein level (CRP) (2.00 mg/dl; N: ! 0.50mg/dl), increased serum levels of �1 and �2-globu-lins and high levels of fibrinogen (525 mg/dl; N:150-450 mg/dl), reduced serum iron (32 �g/dl; N:45-160 �g/dl), reduced hemoglobin (HGB: 12.1gr/dl) and mean corpuscular volume (MCV: 76.4Fl; N :82-92 fL) with mild-anis and poikilocytosishypochromia red series.Serum levels of testosterone, dehydroepiandros-terone sulphate and SHBG (Sex Hormone BindingGlobulin) showed no abnormalities.Following our suggestion to start treatment withisotretinoin, patient’s mother declined her consentand the patient was initially treated with broad-spectrum antibiotics and corticosteroids. After 8weeks of tratment with oral erythromycin (1200mg/day), oral prednisone (0.5 mg/kg daily) and

topical erythromycin (2 applications/day), thelesions showed some improvement but not clear-ing. The mother of the patient then agreed to useoral isotretinoin that was started (2 mg/kg daily),while oral prednisone was stepwise reduced andthen discontinued. After 8 weeks a good clinicalresponse with no significant side effects wasobtained (Figure 3).

Discussion

Acne fulminans (AF) is a rare severe formof acne associated with systemic symptoms thatprimarily affects male adolescents. Although itscause remains unknown, many pathogenetichypothesis have been suggested. In view of theseveral reports of AF in monozygotic twins, hered-itary factors and genetic predisposition have beenconsidered to play a role. In addition, AF has beenreported in two siblings with the same HLA pheno-types4. Hormonal factors may also play a role5. Acrucial pathogenetic step is the rupture of micro-comedon, that eventually results in an extensive,spreading, liquefying necrosis, engulfing neigh-


Volume 2, n. 1, 2011

Figure 2a-b-c.Multiple papules and pustules sometimesconfluent on the chest and face.

2a 2b

2c

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boring follicles and causing a deep inflammationthat involves the adjacent pilo-sebaceous units6.Clinically AF may resemble acne conglobata at itsonset. Patients often complain of various systemicsymptoms, such as fatigue, malaise, arthralgias,myalgias, fever, weight loss and hepatospleno-megaly7. Joint swellings, mainly located in theiliosacral, iliac, and knee joints may be present;erythema nodosum may sometimes coexist8. Also,AF may represent the cutaneous manifestation ofthe synovitis-acne-pustulosis-hyperostosis-osteitis(SAPHO) syndrome9.None of these symptoms, but mild fever, were pre-sent in our patient. Common laboratory findingsinclude anemia, leukocytosis, elevated erythrocytesedimentation rate (ESR), increased levels of C-reactive protein, elevated levels of liver enzymes,thrombocytosis, microscopic hematuria and a nor-mochromic, normocytic anemia10.Serum proteins are usually normal, but decreasedalbumin or increased � and � globulin may beobserved, as in our patient. Differential diagnosisincludes acne conglobata, rosacea fulminans, andproliferative granulation tissue from the use ofisotretinoin to treat acne conglobata1.

Patients with AF are responsive to oral isotretinoin,and best results are obtained when isotretinoin iscombined with systemic corticosteroids11. In gen-eral, treatment starts with a course of prednisolone0.5-1.0 mg/kg for 4-6 weeks. Steroids are thengradually tapered over the following 2 weeks, andisotretinoin, first introduced at a dosage of 0.5mg/kg body weight/day, may gradually beincreased to 1 mg/kg/day according to the clinicalresponse12.To avoid any relapses, duration of such treatmentshould not be withdrawn before 3-5 months.Prognosis, properly treated of AF, is generallygood, although acute inflammatory nodules oftenheal with residual scarring13.This phenomenon occurred in our patient, whoshowed almost complete clearing of skin lesionswith residual scarring particularly evident on hisback (Figure 4).

Conclusions

Treatment of AF should be aimed atachieving clearance of clinical manifestation, pre-


Volume 2, n. 1, 2011

Figure 3a-b.Treatment led to optimal clinical responsewith no significant side effects.

Figure 4.Residual scarring particularly evidenton the back.

3a 3b 4

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9. Iqbal M, Kolodney MS. Acne fulminans with synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome treated withinfliximab. J Am Acad Dermatol 2005; 52:S118-20.

10. Neely GM, Hein MS. Acne fulminans: a case report. S DMed 2006; 59:387-9.

11. Cordoliani F. Acne fulminans therapy. Ann DermatolVenereol 2002; 129:89-92

12. Layton AM. The use of isotretinoin in acne. Dermato-Endocrinology 2009; 1:3, 162-169.

13. Layton AM. Optimal management of acne to prevent scarringand psychological sequelae. Am J Clin Dermatol 2001; 2:135-41.

14. Thiboutot D, Gollnick H, Bettoli V, et al. New insights intothe management of acne: an update from the Global Alliance toImprove Outcomes in Acne group. J Am Acad Dermatol 2009;60:S1-50

15. Niemeier V, Kupfer J, Demmelbauer-Ebner M, et al. Copingwith acne vulgaris: evaluation of the chronic skin disorder ques-tionnaire in patients with acne. Dermatology 1998; 196:108-15.

References

1. Jansen T, Plewig G. Acne fulminans. Int J Dermatol 1998;37:254-7.

2. Plewig G, Kligman AM. Acne fulminans. In: Plewig G,Kligman AM: Acne. Springer-Verlag Ed, Berlin, 1975.

5. Faure M. Acne and hormones. Rev Prat. 2002; 52:850-3.

3. Mehrany K, Kist JM, Weenig RH, Witman PM. Acne fulmi-nans. Int J Dermatol 2005; 44:132-3.

4. Zaba R, Schwartz R, Jarmuda S, et al. Acne fulminans:explosive systemic form of acne. J Eur Acad Dermatol Venereol2010. [Epub ahead of print]

6. Cunliffe WJ, Gollnick H. Acne fulminans. In: Cunliffe WJ:Acne. Diagnosis and Management. Martin Dunitz Ltd Ed,London, England, 2001.

7. Thomson KF, Cunliffe WJ. Acne fulminans “sine fulminans”.Clin Exp Dermatol 2000; 25:299-301.

8. Tan BB, Lear JT, Smith AG. Acne fulminans and erythemanodosum during isotretinoin therapy responding to dapsone.Clin Exp Dermatol 1997; 22:26-7.


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vention of scarring and relief from any physicaland psychological stress resulting from this disor-der13. It has been suggested that an early andaggressive treatment of AF could limit the durationof active acne and reduce the likelihood of physicaland emotional scarring14.Our experience with this single case confirms thatthe combination of prednisone and isotretinoin

may lead to a faster control of local and systemicmanifestations of AF15.Interestingly we experienced considerable con-cerns by patients or their parents to use oralisotretinoin no matter how severe was the clinicalpresentation. For these reasons, we wish to raisethe attention of young dermatologists about possi-ble occurrence.

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