Dermatomyositis

Dermatomyositis

Key Points

  • Dermatomyositis is an autoimmune disease with characteristic cutaneous findings, which also frequently affects the muscles.
  • Dermatomyositis can be a sign of internal malignancy, with 20% of patients having an associated cancer (ovarian cancer risk, in particular, is elevated).
  • Patients require thorough evaluation for extracutaneous disease, including examination of the muscles, joints, lungs, and malignancy screening.

Introduction

Dermatomyositis is an autoimmune disease of unknown etiology characterized by varying amounts of skin and muscle inflammation, which may be associated with other systemic inflammation and/or malignancy. The etiopathogenesis of dermatomyositis is unknown. It is believed that self-proteins become auto-antigens, which may vary by organ or tissue type; the disease is characterized by a type I interferon signature, and C5b-9 deposition has been demonstrated in skin vessels. As with many autoimmune diseases, rates are higher in women, but the true incidence is unknown.

Hallmark skin findings include:

  • The heliotrope eruption (violaceous erythema of the eyelids which can extend to the face)
  • Gottron’s papules (flat-topped papules over the interphalangeal joints or extensor joints)
  • Gottron’s sign (non-papular violaceous erythema on the extensor surfaces of joints)
  • Mechanic’s hands (hyperkeratosis of the sides of the fingers)
  • Samitz’s sign (ragged, frayed cuticles)
  • Proximal nail fold erythema and periungual telangiectasias
  • Shawl sign (violaceous erythema of the V-neck of the chest and upper back/lateral deltoids)
  • Holster sign (erythema of the lateral hips/thighs)
  • Marked photosensitivity which may lead to chronic poikilodermatous skin changes
  • Pruritic erythema of the scalp

Involvement of the skin overlying the extensor joints, the proximal nail fold, the scalp, upper back, and periorbital area is common. The skin findings are typically associated with pruritus. Patients with long-standing disease, or pediatric patients, may develop calcinosis cutis within sites of dermatomyositis inflammation. It is important to distinguish the cutaneous manifestations of dermatomyositis from those of systemic lupus. Unlike the malar rash of lupus, the facial erythema of dermatomyositis tends not to spare the nasolabial creases; while the rash of dermatomyositis tends to be over the joints themselves, erythema from lupus tends to appear on the skin between the interphalangeal joints.

Patients may present with predominantly skin disease with little or no muscle disease (hypomyopathic or amyopathic dermatomyositis, respectively), or with more muscle inflammation (resembling pure inflammatory myositis such as polymyositis). Amyopathic dermatomyositis makes up about 20% of all dermatomyositis patients, and in some centers may be as common as classic dermatomyositis; recognition of the cutaneous features even in absence of muscle inflammation is essential. Patients also often have arthralgia and variable arthritis. In adults, 20% of patients with dermatomyositis have an underlying malignancy, and the condition may be the first sign of cancer. All patients with dermatomyositis should undergo a thorough history and review of systems; medication-induced dermatomyositis is rare, but has been described. Patients should undergo age- appropriate malignancy screening as well. Ovarian cancer is strongly associated with dermatomyositis, and patients should undergo targeted screening of the abdomen and pelvis as well. Beyond the skin and muscle inflammation, arthritis, and potential for malignancy, some phenotypes of dermatomyositis are also associated with interstitial lung disease, which may be rapidly progressive. All patients should undergo baseline pulmonary imaging and pulmonary function testing (including measurement of diffusion capacity). Amyopathic dermatomyositis may go unrecognized, particularly by non-dermatologists. These patients are still at risk of interstitial lung disease and internal malignancy, and need to be both treated for their skin disease and screened for systemic complications.

In general the evaluation of patients with suspected dermatomyositis starts with a thorough physical exam (for the signs noted above, as well as for overt muscle weakness). All patients should undergo laboratory evaluation for signs of muscle inflammation. Creatine kinase is frequently elevated in the presence of active muscle inflammation; aldolase may be a more sensitive marker. Some patients will demonstrate a transaminitis; while those are normally thought of as “liver function tests,” it is important to remember the possibility of elevations in transaminases due to severe muscle inflammation and breakdown. If there is extensive muscle damage, further evaluation for secondary issues is warranted (e.g., renal function to ensure no rhabdomyolysis). In patients with suspected muscle disease whose enzymes are normal, options for further testing include MRI of the weakened muscle and possible muscle biopsy. If those tests are negative, an EMG may demonstrate subclinical myositis. Importantly, patients with longstanding dermatomyositis may have already experienced muscle damage and destruction in the past, and their weakness may be due, not to active inflammation, but to prior disease activity. Rarely, some medications used to treat dermatomyositis can cause muscle symptoms, including both corticosteroids and, uncommonly, hydroxychloroquine. While the myositis tends to affect large, proximal muscles, rarely, patients may experience weakness of other muscles, leading to atypical symptoms such as dysphagia.

Serologic testing may be helpful in dermatomyositis, with emerging research suggesting that detailed myositis-specific antibody profiling may reveal disease-specific autoantibodies that, in some cases, can help predict the clinical phenotype.

Many (but not all) patients with dermatomyositis will be ANA positive. Recent work has highlighted some specific autoantibodies that may be found in approximately 70% of patients with dermatomyositis, and which may correlate to certain clinical phenotypes. Patients with anti-tRNA synthetase antibodies (including Jo-1) have higher rates of interstitial lung disease, arthritis, Raynaud’s, and mechanic’s hands. Patients with Mi-2 antibodies tend to have classic skin findings and a favorable prognosis with treatment responsive disease. The recently described TIF1-γ and NXP-2 may mark adult patients with higher risk for paraneoplastic dermatomyositis. The anti-MDA-5 (CADM-140) may be associated with amyopathic disease. These patients may have higher rates of interstitial lung disease which may be rapidly progressive and potentially fatal. Anti-Ku antibodies may correlate with patients at risk of sclero-dermatomyositis overlap syndrome. There are efforts underway to describe the cutaneous phenotypes that correlate with specific antibody profiles.

If the diagnosis is in doubt, a skin biopsy may sometimes be helpful. Histopathologically, dermatomyositis is characterized by an interface dermatitis with lymphocytes tagging the basal keratinocytes at the dermal/epidermal junction, accompanied by varying amounts of mucin. Notably, biopsy cannot distinguish between dermatomyositis and lupus.