- 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.
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; 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.
The recently described TIF1-γ and NXP-2 may mark adult patients with higher risk for paraneoplastic dermatomyositis. 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.
Therapy of dermatomyositis is determined by which organs are involved, and includes immunomodulatory agents such as antimalarials (hydroxychloroquine, quinacrine, chloroquine; approximately one-quarter of patients with dermatomyositis may develop an exanthema when exposed to antimalarial agents, however), prednisone, methotrexate, azathioprine, and mycophenolate mofetil. All patients with dermatomyositis require expert multidisciplinary care and should be referred to dermatology, rheumatology, and other specialists based on additional organ involvement (dysphagia may require GI, interstitial lung disease may require pulmonology, rare cardiac or neurological manifestations or treatment related side effects may necessitate additional consultants), and frequently require treatment at a tertiary care referral center. High-dose IVIg has been shown to be beneficial in refractory cases of cutaneous disease, but may not be helpful for muscle inflammation. Alternatively, rituximab may help some patients with recalcitrant muscle disease, but is less effective for skin inflammation. Sun-protective measures are also very important, as UV exposure can trigger or exacerbate the disease.
All patients should undergo malignancy screening; paraneoplastic dermatomyositis should be managed by first treating the underlying malignancy, if present. Drug-induced disease is rare, but if suspected, withdrawal of the offending agent is essential.
All patients with muscle weakness may benefit from rest, but should undergo physical therapy to maintain strength, range of motion, and prevent joint contractures. Patients are all photosensitive and should practice strict sun avoidance with broad-spectrum sunscreens and UV-protective garments.
First-line therapy: Myositis is typically treated with systemic corticosteroids, followed by a steroid-sparing immunosuppressive agent. The choice of agents depends somewhat on what organs are affected; most clinicians use methotrexate, mycophenolate, or azathioprine. For skin disease, hydroxychloroquine may be used, though roughly one-quarter of recipients will experience a drug rash. Topical corticosteroids may provide some additional relief. Methotrexate is first-line for skin disease if anti-malarial therapy fails. This article will focus primarily on the cutaneous manifestations; patients with significant muscle disease should be co-managed with a rheumatologist.
- Strict UV protection with broad spectrum, extended UVA-blocking sunscreen and sun-protective clothing.
- Antimalarials (hydroxychloroquine 400 mg daily, limited by ideal body weight up to 6.5 mg/kg/d); 25% of patients may develop a drug rash.
- Symptomatic use of medium-potency topical corticosteroids.
- Methotrexate may be beneficial to patients with widespread skin disease or skin disease which fails to respond to first-line treatment or in patients who cannot tolerate antimalarials. Methotrexate can help muscle disease and arthritis. As methotrexate may rarely be associated with the development of interstitial lung disease, ensure patients have been evaluated for dermatomyositis-associated lung disease prior to initiating treatment.
- Mycophenolate mofetil may be helpful for skin disease, and may have added benefits in patients with concomitant interstitial lung disease.
- Patients with the most severe disease, or those who fail to respond to methotrexate or mycophenolate, may be candidates for treatment with intravenous immunoglobulin.
- Antimalarial therapy is frequently associated with a drug-induced exanthema which should prompt medication change.
- Methotrexate may rarely induce an interstitial pattern of lung disease; as dermatomyositis frequently affects the lungs and may in some cases cause a similar pattern of inflammation, clinicians should ensure their patients have up-to-date pulmonary evaluation (often including pulmonary function testing, CT imaging, and evaluation by an experienced pulmonologist) prior to starting methotrexate.
- Patients with longstanding disease can develop calcinosis cutis, which is often extremely recalcitrant to treatment.
- Corticosteroids can induce a myopathy, and it is important to attempt to distinguish disease-related muscle symptoms for treatment-induced muscle disease.
- 54-year-old white woman
- No significant past medical history
- Review of systems reveals fatigue and weakness with mild arthralgias of the wrists and ankles
- Social history is unremarkable
- Presents for evaluation of pruritic erythema of her scalp and what she describes as “warts” on her fingers. The lesions were first noted about 4 months ago. They are also mildly pruritic. The patient tried over-the-counter wart removal treatments without relief
- Healthy appearing woman
- Erythematous-to-slightly violaceous patches throughout the scalp, including the back of the neck and upper back
- There is erythema and flat-topped papules over the interphalangeal joints
- The proximal nail folds demonstrate violaceous erythema and thrombosed capillaries
- There is mild hyperkeratotic thickening of the lateral fingers and thumb
- Obtain chest imaging and pulmonary function testing to evaluate for interstitial lung disease
- Order CK and aldolase along with basic labs
- Refer patient to dermatology for complete skin exam and biopsy of a representative skin lesion (such as the upper back)
- Conduct age-appropriate malignancy screening, and ensure that she also has ultrasonography of the ovaries
- The patient has a normal CK but mildly elevated aldolase, consistent with hypomyopathic dermatomyositis; a follow-up MRI fails to demonstrate significant muscle inflammation
- The patient has interstitial lung disease on high resolution chest CT and a slightly diminished DLCO on pulmonary function testing
- Her age-appropriate malignancy screening is negative
- Initiate treatment with strict sun protection, trial of topical steroids to affected areas, and start hydroxychloroquine for initial treatment of skin disease. The patient is referred to rheumatology and pulmonology
- The patient should be followed closely by multiple specialties (dermatology, rheumatology, pulmonology), and should have careful monitoring for malignancy for at least the first 3 years after diagnosis
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