Systemic Sclerosis

Case scenarioManjees,27 yrsD1/1Duration of illness-5 yearsc/o raynaud’s phenomenon+fingertip ulcerationNot a/w pain,h/o digital gangrenea/w skin binding down started from B/L forearms gradually

increasing over the course of 4-5 years to involve whole body

Restriction of hand and wrist movementsBreathlessness Difficulty in swallowing with vomiting

Introduction

• Chronic systemic connective tissue disorder.

• Characterised by thickening of the skin(scleroderma)

and distinctive involvement of multiple internal

organs most notably lungs,GIT, heart, kidneys.

Background

• Scleroderma is derived from the greek words

skleros(hard or indurated) and derma(skin).

• Hippocrates first described this condition as thickened

skin.

• First detailed description by Carlo Curzio in 1752.

• Systemic nature of the disease by Robert H.Goetz.

Definition • Multisystemic,autoimmune disease in which there is

increased fibroblast activity which results in

o Vascular damage

o Collagen accumulation

o Scarring of skin and fibrosis

Fibroblasts

• Type of cell that synthesises the collagen & extra cellular matrix.

• Common cells of connective tissue in animals.

Collagen

• Main structural protein in various connective tissues in animal

bodies.

• Found in tendons,ligaments,skin, cornea, cartilage, bone, blood

vessels, gut,inter vertebral disc & dentin.

Functions of collagen

Systemic Sclerosis• Increased fibroblast activity resulting in abnormal

growth of connective tissue.

• This causes vascular damage and fibrosis. Fibrosis occurs in skin, the gastrointestinal tract and other internal organs.

Epidemiology

• Aquired sporadic disease.• Affects all races.• Incidence is 9-19 cases/million/year.• Female predominance(4-5:1).• Peak age 35 -64 yrs.• African american > whites.• Juvenile onset systemic sclerosis is uncommon.

Etiology

• Unknown cause.

• Genetic predisposition

• Enviornmental factors

Viruses(cytomegalo virus)

Chemicals(vinyl chloride,pesticides,silca)

Drugs(cocaine,appetite suppressants,vitK)

Pathophysiology

Classification

According to the extent of skin involvement

• Limited cutaneous systemic sclerosis (lcSSc), or

limited scleroderma

• Diffuse cutaneous systemic sclerosis (dcSSc), or

diffuse scleroderma

• Other types

Limited cutaneous systemic sclerosis

• 70% of SSc cases.

• Milder disease, with less organ involvement

• Slow onset and slow progression

• Affects distal to the elbows and the knee.

• Perioral involvement

• No trunk involvement

CREST syndrome

• C- Calcinosis

• R- Raynaud’s Phenomenon

• E- Esophageal Dysmotility

• S- Sclerodactyly

• T- Telangiectasisa

Calcinosis in X Ray

Raynaud’s Phenomenon

Diffuse cutaneous systemic sclerosis

• 30% of systemic sclerosis cases.

• More rapid onset.

• Skin thickening and Raynaud's phenomenon occurring together or within a short interval.

• Proximal to elbows and knees

• Involves trunk.

• Internal organ involvement is more common.

Limited and Diffuse cutaneous systemic sclerosis

Other types• Rarer type.

• Includes systemic sclerosis sine scleroderma

• Internal organ involvement without the skin changes

Organs involved

• Skin

• Musculoskeletal

• Pulmonary

• Renal

• Gastrointestinal

• Cardiac

Clinical manifestations

General features

• Fatigue.

• Weight loss.

Skin features

Signs in hand

• Raynaud's phenomenon • Swelling (non-pitting oedema) of fingers and toes • Hard and thickened skin • Reduced hand movements- the 'prayer sign(patients

may be unable to place the palmar surfaces together)• Fingertips may have pitting, ulcers or loss of bulk

from finger pads.

• Calcinosis• Face and mouth:

– Tightening of facial skin.– Tight lips (microstomia)

• Telangiectasia.• 'Salt and pepper' appearance of skin, due to areas of

hypopigmentation and hyperpigmentation.• Dry or itchy skin; reduced hair over affected skin

areas.

Musculoskeletal features

• Joint pain and swelling• Myalgia • Restriction of joint movement, contractures and

muscle atrophy due to skin sclerosis• Tendon friction rubs - palpable/audible over the

flexor/extensor tendons of the hands, knees and ankles.

GI features

• Heartburn and reflux oesophagitis.

• Oesophageal scarring and dysphagia.

• Delayed gastric emptying - eg, fullness after meals.

• Esophageal dysmotility - can cause bacterial overgrowth,

malabsorption, diarrhoea and malnutrition.

• Constipation due to reduced colonic motility.

Pulmonary features

• Interstitial lung disease:

– Occurs in as many as 75% of scleroderma patients

– Causes restrictive lung disease

– Causes fibrosis of lungs

– Symptoms and signs: exertional dyspnoea, cough,

coarse basal crackles.

Pulmonary features

• Pulmonary arterial hypertension (PAH):

– Occurs in about 10-15% of patients with scleroderma

– A leading cause of death in SSc

– Due to narrowing of vessel as a result of intimal fibrosis

– Symptoms and signs: exertional dyspnoea,

syncope, right ventricular strain features

Renal manifestations• Scleroderma Renal Crisis

Abruptly developing severe hypertension-Rise in SBP by > 30 mmHg, DBP by > 20 mm Hg

Signs &Symptoms – o Increase in serum creatinine by 50% over baseline or

creatinine > 20% of upper limit. oProteinuria > 2+ by dipstick. oHematuria > 10 RBC/HPFoThrombocytopenia < 100oHemolysis

Cardiac Manifestations

• Pericardial Effusion

• Microvascular coronary aretery disease

• Myocarditis

• Arrhythmias and conduction abnormalities

Assessment and diagnostic findings

• Physical examination- clinical manifestations

• Blood tests

• Autoantibodies:

– Antinuclear antibody

– Other autoantibodies in SSc

Assessment and diagnostic findings

• Respiratory system-HRCT,PFT,Chest X-Ray• GI system-barium swallow,esophageal manometry• Renal system-urine examination,24 –hr urine protein,

renal function test.• Cardio vascular system-ECG,ECHO• Musculo skeletal system-X-Ray of joints,muscle

enzymes.

Regular monitoring

• Renal function.

• Lung function tests and chest CT scan.

• ECG and echocardiography.

Diagnostic criteria

• The american college of rheumatology criteria for the

classification of systemic sclerosis.

• One major criteria and two minor criteria for

diagnosis.

Major criterion• Proximal scleroderma

Symmetrical thickening

Tightening

Induration of the skin of the fingers and the skin

proximal to the MCP/MTP joints.

Change may affect the entire extremity,face , neck

and trunk.

Minor criterion• Sclerodactyly-thickening,induration,tightening of the

skin limited only to fingers.

• Digital pitting scars/loss of substance from the finger

pad-due to ischemia

• Bibasilar pulmonary fibrosis-B/L reticular pattern of

linear densities in basilar portions of the lung on

CXR.diffuse mottling/honey comb lung not

attributable to pulmonary disease.

Early diagnosis - the VEDOSS initiative

The VEDOSS (Very Early Diagnosis Of Systemic Sclerosis) initiative in Europe identified the following features as being key to diagnosing SSc in the very early stage:

Puffy fingers in Raynaud's syndrome patients.Antinuclear antibodies.Scleroderma-specific antibodies.SSc pattern on nailfold capillaroscopy.

Case scenario

Ba swallow – normal, but pt. was having dysphagia

HRCT – inflammatory lung disease(early)

ANA – diffuse 2+(1:80)

ds DNA – 12.5 IU/ml

2D ECHO – 45 to 50 % EF

Physical examinations

• Generalized binding down of skin predominantly the

fingers

• Salt and pepper appearance on nose/ear

• Shortening of digits

• Fixed flexion deformity of interphalangeal joint

• Ulcer in digits

Management

• Controlling symptoms

• Preventing complications.

Scleroderma Treatment

• Depends on clinical manifestations

Monitoring

• Regular review of symptoms.

• Blood pressure monitoring.

• Renal function monitoring.

• Lung function tests and chest CT scan.

• ECG and echocardiography.

• To relieve symptoms

Raynaud’s• Calcium Channel Blockers: nifedipine

• Sildenafil (Viagra 0.25 mg TDS) –mainly in patients

with PAH,relaxes blood vessels in lungs

• Parental vasodilators (iloprost) – for severe disease

with impending digital ischemia (25 µg intravenous for

3 to 5 days every 3 months)

• Trental (pentoxifylline)Vaso active drug

Xanthine derivativeIndicated in chronic occlusive peripheral vascular

disordersImproves blood flow

Starting dose-400 mg BD after mealsUsual dose-400 mg TDS

Efficacy and safety of sildenafil in patients with systemic scleroderma

Aim:To retrospectively analyze the efficacy and safety of sildenafil (sf) in patients with systemic sclerosis (SS).

Sf was used in 16 patients aged 20-66 years with SS of a duration of 2 months to 27 years. The indications for Sf treatment were significant Raynaud's phenomenon (RP) in 3 patients, digital ulcers (DU) and/or necrosis (N) in 9, pulmonary hypertension (PH) in 5 and critical ischemia of the left fingers in 1 patient. RP was seen in all the patients and so the effect of Sf on the course of RP was evaluated in the whole patient group.

RESULTS:There was a significant decrease in the frequency and intensity of Raynaud's attacks in 11 of the 15 patients treated with Sf. All 7 patients with DUs showed a decrease in their sizes just within the first two weeks of treatment. Complete DU healing was observed within 4-12 weeks of treatment. Pain ceased just within the first 5-7 days of treatment. Sf resulted in a rapid reduction in systolic pulmonary artery pressure (sPAP). In a case, Sf was discontinued because of dizziness after its first intake in a dose of 12.5 mg. The initial drug intake of the drug was not followed by adverse reactions in 12 (75%) of the 16 patients. Four patients had Sf-induced complaints, including headache, dizziness , and more severe angina pectoris .

CONCLUSION:Sf is an effective drug to treat the manifestations of scleroderma vasculopathy, such as RP, DU/N, and PH. Sf is well tolerated in most cases. The SS patients with pronounced ECG changes have an increased risk of severe cardiac events and they need careful ECG monitoring.

Gastrointestinal Involvement

Proton pump inhibitor-omeprazole

Mozapride(5 mg TDS)-gastro prokinetic agent,

accelarate gastric emptying

Cardiac Involvement. Pericarditis:

• NSAIDs• Drainage of effusion if tamponade

• Prevent the condition from progressing

• Treatments are used which suppress the body's immune system

SteroidsMethotrexateAzathioprineMycophenolate mofetilCiclosporinCyclophosphamide

Dexona pulse

• Dexamethasone pulse therapy consists of the intravenous administration of 100 mg dexamethasone dissolved in 500 ml of 5% dextrose on 3 consecutive days. The pulses are repeated every 4 weeks.

• To detect and treat complications early

• Skin: dressings and antibiotic medicines are used for skin ulcers. Surgery for tight skin, nodules or ulcers.

• Lungs: new medicines such as bosentan, sildenafil, iloprost and have improved the treatment of pulmonary hypertension.

• High blood pressure and kidney problems are treated with angiotensin-converting enzyme (ACE) inhibitor.

• Thyroid replacement tablets are given for an underactive thyroid gland.

• Should receive antibiotics because more susceptible to infection.

• Minimise disability

• Exercises to keep joints mobile and muscles strong.• Various aids such as splints to support the joints, and

help with daily living tasks.• Regular dental checks if pt.has dry mouth symptoms.• Patient support groups, such as the Raynaud's and

Scleroderma Association or the Scleroderma Society, can provide information and support.

• Patient education/self-management programmes.

• Nutritional advice, and supplements if needed.• For Raynaud's phenomenon:– Prevention - avoid cold and trauma; use warm

clothing or heated clothing(gloves).– For an attack - warm the body, hands and

feet gently (the skin may be numb and unable to feel if the heat source is too hot); use gentle arm movements or gentle massage to help restore circulation.

Case Scenario-Tx historyT. Depin QID 4 monhs

T. Trental 400mg BD 4months

T. Pantocid for 1 year

T.Endoxan 50 BD 4months

T.Betnesol forte –sat&sunday

Mild to no improvement

Increased course of disease leads to increased ulceration

Currently –

T. Depin 10 mg BD

T.Pan 40 1 BBF

T.Flexon SOS

T. Endoxan 50mg OD

Condey’s compress

Cold protection

Life style and home remedies• Stay active- Range-of-motion exercises can help keep

your skin and joints flexible.• Don't smoke- Nicotine causes blood vessels to

contract, making Raynaud's phenomenon worse. • Manage heartburn- Avoid foods that causes gas.

Avoid late-night meals. Elevate the head of your bed .Antacids may relieve symptoms.

• Protect yourself from the cold- Wear warm clothes for protection anytime your hands are exposed to cold.

New initiative

In 4th systemic sclerosis world congress held in Lisbon on Feb. 2016 a paper was presented titled Pan PPAR agonist IVA337 has an anti‐fibrotic effect in multiple in vitro and in vivo fibrosis models.

IVA337, is an anti-fibrotic drug with a unique mechanism of action by activating all three alpha, gamma, and delta PPARs (peroxisome proliferator‐activated receptors), receptors that play key roles in controlling the fibrotic process.

Prevention of Digital Ulcers in Systemic Sclerosis: Real Life Data From the

Observational Study of the EUSTAR group,Recurrent digital ulcers are a manifestation of vascular disease in patients with systemic sclerosis. Digital ulcers are usually managed with endothelin receptor antagonists, such as Bosentan or Sildenafil or both, iloprost and other drugs, like calcium channel blockers (CCB) and ACE inhibitors (ACEI).The study examined the efficacy of Sildenafil,Bosentan,Sildenafil plus Bosentan,iliprost,and CCB/ACEI in the prevention of new digital ulcers in systemic sclerosis patients. 268 pts. are assessed, 47 on Bosentan,33 on Sildenafil, 40 on iloprost, 31 on Sildenafil plus Bosentan and 117 on CCB/ACEI alone.They found that treatment with CCB/ACEI alone was found to be statistically associated with a 7.1 percent increase in the risk of developing new digital ulcers, compared to all the other treatments tested.

Effect of Fat and Stromal Vascular Fraction For Systemic Sclerosis Manifestations in Face and Hands

 Systemic sclerosis patients were treated with fat and stromal vascular fraction — a component of the lipoaspirate obtained from liposuction of excess adipose tissue that contains mostly stem cells and growth factors. The growth factors are very important signaling molecules that can turn on and off inflammation and cause cells to grow or die.In total, 14 patients were treated via micro- injection of 16 to 22 cc of fat, and 12 patients’ hands were treated with the stromal vascular fraction.They reported that a continuous improvement was observed in the face of systemic sclerosis patients, primarily a reduction of pain and improvement in function, and as a consequence, a noticeable improvement in quality of life.

Nursing management• Altered skin integrity related to inflammation, vaso

constriction

• Altered peripheral tissue perfusion r/t vasospasm and structural changes

• Joint pain r/t inflammation early in disease

• Joint stiffness r/t inflammation in early diseaseand contracture in advancing disease

Altered skin integrity related to inflammation, vaso constriction

Assess skin,noting color, moisture, texture, temp, note redness,swelling or tenderness

Assess skin for any breaks in integrity.Note presence of any ulcers,size,any drainage and amount of ecrotic ttissue

Solicit pt’s description of pain expressed as itching or burning followed by inflammation

Assess interference with life style.Patient may develop contractures from their tight skin

• Provide prophylactic pressure relieving devices(special mattress,elbow pad)

• Maintain fnl.body alignment• Clean,dry and moisturize intact skin with warm water

esp. over bony prominences • Use unscented solution,scented lotions contain

alcohol which dries skin• Encourage adequate nutrition and hydration,which

keeps the skin moist• Use non affected skin areas for injection,penetration

may cause further skin damage• Assist with ADLs as needed• Tell pt. To avoid direct contact with harsh chemicals

Altered peripheral tissue perfusion r/t vasospasm and structural changes

• Assess hands and feet for color,temp. And skin integrity

• Remove vaso consticting factors when possible• Keep extremities warm• Administer vasodilating medications(Ca channel

blockers)• Instruct pts. To avoid undue cold exposure• Wear oven mitts for refrigerator

• Wear multiple layers of clothing in cold enviornment• Wear items made of wool,cotton• Instruct patient to avoid caffeine and nicotine(cause

vaso constriction)• Instruct patient in stress management• Refer to specialized programme as needed

Joint pain r/t inflammation early in disease

• Assess for signs of joint inflammation(redness, warmth, swelling, decreased motion)

• Determine past pain relief measures• Assess interference with life style• Administer anti inflammatory medications as

prescribed• Use non narcotic analgesics as necessary• Encourage anatomically correct position of joints

• Encourage use of ambulation aids when pain related to weight bearing

• Encourage use of alternate methods of pain control such as relaxation,guided imagery

• Apply bed cradle to keep pressure of bed covers off inflamed lower extremities

• Consult occupational therapists for proper splinting of affected joints

Joint stiffness r/t inflammation in early disease and contracture in advancing disease• Assess location;generalized or localized• Assess timing;moning,night,whole day• Duration of stiffness• Encourage pt. to take 15 min warm bath on rising• Encourage to perform ROM exercises after bath• Allow sufficient time for all activities• Avoid scheduling tests or treatments when stiffness is

present• Administer anti inflammatory medications• Remind patient to avoid prolonged inactivity

Thank you