Journal of Pakistan Association of Dermatologists 2008; 18: 33-43.

Review Article Dermatomyositis Muhammad Arif Maan, Shahid Javaid Akhtar, Hina Haque

Department of Dermatology, Punjab Medical College, Faisalabad

Abstract Dermatomyositis (DM) is an idiopathic inflammatory disease affecting primarily the muscles. It is accompanied by many cutaneous changes some of which are pathognomonic for DM. Clinically it has a wide range of manifestation. In certain patients it is associated with some internal malignancy. The present review focuses on the diverse cutaneous signs seen in DM.

Key words Dermatomyositis, Gottron papules, helitrope erythema

Definition implicated in the etiology. There seems to be a genetic predisposition linked to certain Dermatomyositis (DM) is a disorder mainly HLA types e.g. DR3, DR5, DR7. Abnormal of skin, muscle and blood vessels in which T-cell activity may be involved in characteristic erythematous and edematous pathogenesis of both skin and muscle changes in skin are associated with muscle disease. Autoantibodies to nuclear and weakness and inflammation.1 cytoplasmic antigens may be present. Infectious agents such as Toxoplasma and Epidemiology Borrelia species and viruses such as coxsackie virus, parvovirus, echovirus, There has been an increase in the incidence HTLV-1 (human T-cell lymphotropic virus) of DM worldwide. Estimated incidence in and HIV may have a role. Cases of drug- the US is estimated to be 5.5 per million. In induced disease have been reported with children under 16 years of age, it is 1.9 per hydroxyurea (in patients with CML or million. DM can affect any age group. Two essential thrombocytosis), penicillamine, peak ages of onset exist. The peak age of statin drugs, quinidine and phenylbutazone. onset in adults is 50 years and in children it Dermatomyositis may be initiated or is 5-10 years. Median age of onset is 6.8 exacerbated by silicone breast implants or years. Males are affected twice as often as collagen injections.2,3 females. Mean age of onset is later in men than in women.1,2,3 Classification

Etiology Dermatomyositis has been classified in different ways. A practical approach is to The cause of dermatomyositis is unknown. divide it into adult-onset and juvenile-onset. However, a few factors have been Each group is further divided into Address for correspondence subgroups. Dr. Muhammad Arif Maan, Department of Dermatology, Punjab Medical College, Faisalabad, Pakistan.

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Adult onset Rare manifestations • Classic dermatomyositis alone These are follicular , papular • Classic dermatomyositis with mucinosis, hypertrichosis, malignant malignancy erythema, urticarial vasculitis, partial • Classic dermatomyositis of an lipodystrophy, zebra-like striping and vulvar overlap connective tissue disorder or scrotal involvement. • Amyopathic dermatomyositis Compatible manifestations Juvenile onset These are poikiloderma atrophicans 4,5,6 • Classic dermatomyositis vasculare and cutis. • Amyopathic dermatomyositis Gottron papules • Hypomyopathic dermatomyositis7 These are slightly elevated violaceous,

erythematous papules. Common sites are Clinical features metacarpo-phalangeal joints, proximal

interphalangeal joints and distal Skin disease is one of the initial interphalangeal joints (Figure 1). These may manifestations. In 40% patients, skin disease be seen on elbows, knees or feet.4,5,6 A slight may be the sole manifestation at onset. scale, occasionally a thick psoriasiform scale Presenting symptoms may be fever and may be present. These are seen in 70% malaise.2,3 patients of dermatomyositis. Lesions may

resemble lesions of , Skin disease or .2,3

In skin disease, there is history of an Heliotrope rash eruption on exposed surfaces and rash is Heliotrope rash is named after the tendency often pruritic. Intense pruritus may disturb of certain plants to grow towards sun. It is a sleep pattern. There may be history of violaceous to dusky erythematous rash with diffuse hair loss.2,3 or without edema in a symmetrical

distribution involving eyelids, periorbital Pathognomonic manifestations skin, upper cheeks, forehead and temples These are Gottron's papules and Gottron's (Figure 2). Sometimes only a mild sign. discoloration is seen along eyelid margin. Its

presence is highly suggestive of Characteristic manifestations dermatomyositis. Affected areas are These are heliotrope rash, shawl sign/v-sign, typically more sensitive to sun exposure. mechanic's hand and periungual Rash occurs early in the course of disease in telangiectasias. 30-60% patients.2,3

Less common manifestations Mechanic’s hands These are facial swelling, malignancy, These are seen in patients with anti- erythroderma, cutaneous vasculitis and synthetase antibodies. There is panniculitis. hyperkeratosis, fissuring and linear

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Figure 1 Gottron’s papules [4]. Figure 4 Dilated nailfold capillaries and hypertrophic ragged cuticle [4].

Figure 2 Heliotrope erythema with periorbital Figure 5 Calcinosis cutis on palms [4]. edema [4].

Figure 3 Mechanic’s hands which are fissured, scaly, hyperkeratotic and hyperpigmented, suggestive of manual labour [4]. hyperpigmentation of radial and palmar surfaces of fingers (Figure 3).1 Figure 6 Radiograph showing subcutaneous . This is a particular feature of childhood dermatomyositis [4].

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Shawl sign Muscle disease It is erythematous, poikilodermatous macules distributed in a "shawl" pattern over Muscle disease may occur concurrently, the shoulders, arms and upper back.4,5,6 may precede or may follow skin disease by weeks to years. Muscle involvement is V sign manifested by progressive, proximal, It is erythematous, poikilodermatous symmetrical muscle weakness affecting macules distributed in a V-shaped shoulder and pelvic girdles mainly. distribution over the anterior neck and chest. 4,5,6 Patients complain of fatigue of muscles or

weakness while climbing stairs. There is Poikiloderma atrophicans vasculare also difficulty in rising from sitting position, (poikilodermatomyositis) combing hair and reaching for items above This is circumscribed violaceous erythema the shoulders. Muscle tenderness is a with associated telangiectasia, variable finding. Testing of muscle strength hypopigmentation and superficial . It is part of assessment of these patients. is most commonly found over posterior Extensor muscles are more affected than shoulders, back, buttocks, V-shaped area of flexors. Distal strength is almost always the anterior neck and chest and is often a maintained.2,3 late finding.4,5,6

Other systemic features Scalp involvement

Scalp involvement is relatively common. Systemic features of dermatomyositis There is an erythematous to violaceous include arthralgia, arthritis, dyspnea, psoriasiform dermatitis. Non-scarring dysphagia, dysphonia, arrhythmias, alopecia may occur in some patients.2,3,10 abdominal pain and visual changes.4,5,6

Nailfold changes Joint involvement There are periungual telangiectasias. These Joint swelling occurs in some patients. are apparent clinically or are visible only on Small joints of hands are most frequently capillary microscopy (Figure 4). There is involved. Arthritis associated with characteristic cuticular change with dermatomyositis is not erosive or hypertrophy of cuticle and small deforming.2,3 hemorrhagic infarcts.2,3

Juvenile dermatomyositis Calcinosis cutis

Calcinosis cutis occurs in 30-70% cases of Its clinical presentation is usually different juvenile dermatomyositis and in 10% of from presentation of adult type. Skin lesions adult cases. There are firm yellow or white are similar. Common findings are low-grade nodules under the skin and are present on fever, increased risk of gastrointestinal buttocks, elbows, knees or traumatized areas manifestations and symmetric arthritis of (Figure 5). It is associated with increased large and small joints. There is an increased disease activity and duration.4,5,6

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incidence of calcinosis cutis in juvenile patients (Figure 6). Asymptomatic cardiac conduction delays and right bundle branch block is found in 50% patients. There is no association between juvenile dermatomyositis and malignancy.11,12

Histopathology

Skin There is hydropic degeneration of basal cells Figure 7 Focal, mild basal cell hydropic of epidermis, edema of upper dermis, degeneration and a chronic inflammatory cell vascular dilatation and perivascular infiltrate is present in the dermis [4]. inflammatory infiltrate composed mainly of CD4+ T cells and HLA-DR-expressing macrophages. B lymphocytes are absent. Histiocytes, plasma cells and eosinophils are present. PAS-positive fibrinoid deposits are seen at dermo-epidermal junction and around dermal capillaries. There is accumulation of mucopolysaccharides in dermis (evident with use of special stains). Hyperkeratosis, acanthosis, and mild papillomatosis are seen in Gottron’s papules. In later stages there is thickening of collagen of dermis, epidermis becomes atrophic, Figure 8 Hyperkeratosis and epidermal atrophy there is flattening of rete ridges and [4]. increased pigment in basal layer (Figures 7 and 8).1

Muscles In the early stages, there is loss of transverse striation of muscle fibres, hyalinization of sarcoplasm and increase in sarcolemmal nuclei. In late stages, fibres fragment and show granular and vacuolar degeneration (Figure 9). Later, muscle becomes atrophied and sclerosed.1

Figure 9 showing degeneration of muscle bundles with edema and inflammatory cells [4].

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Relationship to malignancy Table 1 Diagnostic criteria for dermatomyositis [4,5,6]. 1. Skin lesions Primary tumour occurs in lungs, breast, i. Heliotrope rash female genital tract, stomach, rectum, ii. Gottron's sign kidney or testis. Dermatomyositis precedes iii. Erythema on the extensor surface of extremity joints, slight raised red- the in 40% cases, both may occur purple erythema over elbows or knees together in 26% cases and neoplasm may 2. Proximal muscle weakness occur first in 34% cases.1,8 3. Elevated serum creatine kinase or aldolase level 4. Muscle pain on grasping or spontaneous pain Complications of dermatomyositis 5. Myogenic changes on electromyography 6. Positive anti-Jo-1 antibody test Complications of dermatomyositis include 7. Nondestructive arthritis or arthralgia 8. Systemic inflammatory signs such as contracted limbs, aspiration pneumonia, temperature more than 37°C [98.6°F] at axilla, type 2 respiratory failure, diffuse interstitial elevated serum C-reactive protein level or ESR pneumonitis, pulmonary fibrosis, of more than 20 mm per hour. 9. Pathological findings compatible with pericarditis, cardiac failure, cardiomyopathy, inflammatory myositis. cardiac conduction defects, vasculitis, large Patients presenting with at least 1 finding from bowel infarction (secondary to the above three and 4 findings from features 2-9 vasculopathy), muscle atrophy, muscle are said to have dermatomyositis. calcification, malnutrition, acute kidney polyarteritis nodosa. 11-40 % pts have a failure, malignancy, Raynaud’s concomitant diagnosis of a connective tissue phenomenon, hypertrichosis and sclerosis of disorder. Overlap syndrome is common in skin. Ocular complications include females. Male to female ratio is 9:1.4,5,6 nystagmus, cotton-wool spots, optic atrophy and conjunctival edema.4,5,6 Differential diagnosis

Amyopathic dermatomyositis Differential diagnosis of dermatomyositis

includes HIV infection (at onset of Amyopathic patients have pathognomonic immunodeficiency), lichen planus, skin changes, without clinical or laboratory Polymorphous light eruption, seborrheic evidence of muscle involvement. It is dermatitis, systemic lupus erythematosus, reported in 2-11% patients. Lethargy, psoriasis, contact dermatitis, atopic pruritus, fatigue, photosensitivity and dermatitis, trichinosis (caused by periorbital arthralgia are the usual presenting swelling and edema), alcohol and drugs that features.4,5,6 can cause myositis (penicillamine, NSAIDS,

hydroxyurea, pravastatin, clofibrate).1,4,5,6 Overlap syndrome

Diagnosis A number of patients with dermatomyositis also meet the criteria for one of the The diagnostic criteria for dermatomyositis connective tissue disorders. These disorders is shown in Table 1. Patients presenting include rheumatoid arthritis, , with at least 1 out of 4 cutaneous findings systemic lupus erythematosus and

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and 4 findings from extracutaneous features vii. Anti-Ku antibodies associated with 2-9 are said to have dermatomyositis. overlap of scleroderma or SLE with dermatomyositis. Evaluation of dermatomyositis 3. ESR Evaluation of dermatomyositis is done on It is elevated in approximately 50% patients the basis of history and physical (does not correlate well with disease examination, chest radiograph, laboratory activity). tests, urine examination especially 24 hour urinary creatine level, skin and muscle 4. Rheumatoid factor biopsy, MRI and electromyography.4,5,6 It is seen in 20% patients, mostly in those with overlap syndrome. Laboratory manifestations of dermatomyositis 5. von Willebrand factor It is reported to correlate with juvenile 1. Muscle enzyme elevation (CPK, serum dermatomyositis. aldolase, LDH, ALT, AST, carbonic anhydrase isoenzyme II) 6. EMG There is myopathic pattern, 10% are false- 2. Autoantibodies negative. i. ANA levels elevated in 60 to 80% of patients with classic 7. Magnetic resonance imaging dermatomyositis It is useful for assessing the presence of an ii. Anti-Jo-1 most common inflammatory myopathy in patients without antisynthetase found; 20% of weakness. It is also useful in differentiating patients with dermatomyositis may steroid myopathy from continued have positive result inflammation and may serve as a guide in iii. Anti-EJ may be more associated selecting a muscle biopsy site.2,3,4,5,6 with typical skin lesions iv. SRP occurring in 5% patients Treatment v. Mi-2 antibodies (a nuclear protein complex): occurring in 15 to 20% of Treatment can be divided into general patients with classic measures and medical treatment. dermatomyositis, associated with a more treatment-responsive form, General measures shawl sign and prominent cuticular Bed rest is valuable for patients with severe changes muscle inflammation. A program of physical vi. Anti-PM-Scl antibodies associated therapy is useful to help prevent with overlap of scleroderma and contractures. Sun avoidance and use of a dermatomyositis. broad-spectrum sunscreen is recommended.

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Table 1 Different systemic medications used in dermatomyositis [4,5,6,9]. Treatment modality Dosage Comments Oral corticosteroids 0.5 to 1.5 mg/kg daily until serum CK Consider adjunctive therapy if no normalizes, then slowly taper over 12 improvement in objective muscle months strength after three months of therapy Methotrexate Oral: 7.5 to 10 mg/week, increased by First-line adjuvant therapy in 2.5 mg/week to total of 25 mg/week patients unresponsive to steroids Intravenous: 10 mg/week, increased by 2.5 mg/week to total of 0.5 to 0.8 mg/kg Azathioprine 2 - 3 mg/kg/day tapered to 1 Screen patients for thiopurine mg/kg/day once steroid is tapered to methyltransferase deficiency 15 mg/day before therapy Cyclophosphamide Oral: 1 -3 mg/kg/day Intravenous: 2 -4 In refractory cases only mg/kg/day, in conjunction with prednisone

Hydroxychloroquine 200 mg twice daily in adults; 2-5 mg/kg/day in children Intravenous immunoglobulin 2 g per kg in divided doses once per month for 3 months

Diet Radiation therapy Diet should be well-balanced. Patients with Irradiation of the lymph nodes is done to severe muscle inflammation may need extra suppress immune system. protein to balance their loss. Patients of dysphagia may require a special diet Fludarabine depending upon the severity of esophageal It prevents the development and growth of dysfunction.13 malignant cells.

Medical treatment Tacrolimus Table 2 shows different drugs used in the This transplant rejection drug may work to management of dermatomyositis. inhibit immune system. Antihistamines are given for control of severe pruritus and pain relievers to treat Monoclonal antibodies associated pain. These are man-made antibodies designed to target and destroy specific types of cells. Dermatomyositis treatment options still under investigation Prognosis

Plasmapheresis The disease may spontaneously remit in It is also called plasma exchange in which 20% of patients. 5% of patients have damaging antibodies are removed from fulminant progressive course with eventual blood. death. Many patients require long-term therapy.2,3

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Poor prognostic indicators Disease, 2nd edn. New York: Saunders, Poor prognostic indicators are recalcitrant 1995. p. 13-20. 5. Sontheimer RD. Dermatomyositis. In: disease, delay in diagnosis, old age, Freedberg IM, Eisen AZ, Wolff K, et malignancy, fever, asthenia, anorexia, al., eds. Fitzpatrick's Dermatology in th pulmonary interstitial fibrosis, dysphagia General Medicine, 5 edn. New York: McGraw-Hill, 1999. p. 2009-20. and leukocytosis. In juvenile 6. Kovacs SO, Kovacs SC. dermatomyositis, late onset of treatment, Dermatomyositis. J Am Acad Dermatol initial treatment with a dosage of 1998; 39: 899-920. 7. Wolff K, Johnson RA, Suurmond D. prednisolone that is too low, recalcitrant Skin signs of immune, autoimmune and disease and pharyngeal involvement are rheumatic diseases. Fitzpatrick’s Color associated with poor prognosis.4,5,6 Atlas and Synopsis of Clinical Dermatology, 5th edition. New York: McGraw-Hill; 2005. p. 356-439. Most common causes of death 8. Savin JA. The skin and systemic Most common causes of death in patients of disease-genetics and skin disease. In: Buxton PK. ed. ABC of Dermatology, dermatomyositis are malignancy, cardiac or 4th edn. London: BMJ Publishing pulmonary dysfunction and infection.4,5,6 Group; 2003. p. 72-81. 9. Sontheimer RD. The management of dermatomyositis: current treatment References options. Expert Opin Pharmacother 2004; 5: 1083-99. 1. Goodfield MJD, Jones SK, Veale DJ. 10. Kasteler JS, Callen JP. Scalp The Connective Tissue Diseases. In: involvement in dermatomyositis. Often Burns T, Breathnach S, Cox N, Griffiths overlooked or misdiagnosed. JAMA C. eds. Rook’s Textbook of 1994; 272: 1939-41. Dermatology. Oxford: Blackwell 11. Halbert AR. Juvenile dermatomyositis. Science; 2004. p. 56.1-56.148. Aust J Dermatol 1996; 37: 106-8. 2. Callen JP, Wortmann RL. 12. Pachman LM. Juvenile Dermatomyositis. Clin Dermatol 2006; dermatomyositis. Pediatr Clin North 24: 363-73. Am 1995; 42: 1071-98. 3. Sontheimer RD. Skin manifestations of 13. Drake LA, Dinehart SM, Farmer ER et systemic autoimmune connective tissue al. Guidelines of care for disease: diagnostics and therapeutics. dermatomyositis. American Academy Best Pract Res Clin Rheumatol 2004; of Dermatology. J Am Acad Dermatol 18: 429-62. 1996; 34: 824-9. 4. Callen JP. Dermatomyositis. In: Callen JP, ed. Dermatological Signs of Internal

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