Evolution of Seronegative Inflammatory Myositis to Dermatomyositis With Characteristic Cutaneous Features: A Case Report

Abstract

Dermatomyositis (DM) is a rare inflammatory myopathy with an incidence of 9.63 per 1 000 000 people and typically presents with skin rash and muscle weakness. We report a case of DM that presented with proximal muscle weakness, normal creatine phosphokinase (CPK), negative myositis antibody panel, and non-specific histopathological findings on muscle biopsy, without initial skin involvement. A 67-year-old male presented with subacute bilateral proximal lower-extremity weakness and weight loss of 20 pounds over 3 months. Laboratory investigation was significant for elevated erythrocyte sedimentation rate, C-reactive protein, CPK, and aldolase, with negative myositis-specific antibodies. Femur magnetic resonance imaging revealed subcutaneous, fascial, and muscle edema throughout quadriceps and gluteal muscles. Muscle biopsy showed myofiber atrophy with perivascular and endomysial T-lymphocytes and histiocytes, as well as scattered necrotic myofibers. He was diagnosed with inflammatory myositis and started on prednisone and monthly IVIG infusions. At 2-month follow-up, he reported new rashes on the extensor surfaces of the hands consistent with Gottron’s papules, mechanic’s hands, and livedo reticularis of feet and arms. Cases of DM that present with myopathy and later develop skin changes are rare. Our patient had several months of progressive proximal muscle weakness, and skin changes occurred after he was started on treatment. Laboratory findings include elevated CPK, aldolase, and myositis-specific auto-antibodies. Muscle biopsy helps in diagnosis; however, findings may be nonspecific—as was the case in our patient. Corticosteroids are first-line treatment. Long-term follow-up studies are necessary to better understand the incidence of late-onset development of typical skin findings.

Introduction

Idiopathic inflammatory myopathy (IIM) is an umbrella term that represents a broad category of different syndromes, most of which manifest with progressive subacute proximal muscle weakness. ¹ Idiopathic inflammatory myopathy include dermatomyositis (DM), polymyositis (PM), overlap myositis, and necrotizing autoimmune myopathy. ¹ Secondary causes of muscle weakness are common, and endocrine, toxic, and infectious causes must be excluded prior to diagnosis. ¹ Dermatomyositis is a rare form of IIM with an incidence of 9.63 per 1 000 000 people and typically presents with skin rash that progresses into muscle weakness within 6 months of onset.^1,2 Etiology is unknown and presumed to be multifactorial, with women more commonly affected than men at a mean age of 40 to 50 years. ² We report a rare case of DM in a male patient who presented with proximal muscle weakness without skin involvement. He was initially found to have negative serology, negative myositis-specific antibody panel, and nonspecific pathohistological findings on muscle biopsy without initial skin involvement.

Case Presentation

A 67-year-old male with a past medical history of hypertension, hyperlipidemia, and type 2 diabetes mellitus, presented to our tertiary care center with subacute bilateral proximal lower-extremity weakness, slow shuffling gait, and unintentional weight loss of 20 pounds over 3 months. The clinical review was unremarkable without any new ocular or bulbar symptoms, arthralgia, myalgia, Raynaud’s phenomenon, or rash. He had no prior history of malignancies, and cancer screening was up to date, including endoscopy and colonoscopy which were done during the admission to rule out paraneoplastic syndromes. Physical examination was significant for decreased muscle strength in the bilateral proximal lower extremities with preserved strength of bilateral distal lower and bilateral upper extremities. No skin rash was noted. Laboratory evaluation is presented in Table 1 and was significant for elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and aldolase with negative myositis-specific antibodies. Electromyography (EMG) demonstrated fibrillations and positive sharp waves in the right vastus lateralis and tibialis anterior consistent with irritable myopathy. Magnetic resonance imaging (MRI) of the femur revealed subcutaneous and fascial edema with diffuse muscle edema throughout quadriceps and gluteal muscles (Image 1). Muscle biopsy of the left vastus lateralis revealed myofiber atrophy with perivascular and endomysial T-lymphocytes and histiocytes, as well as scattered necrotic myofibers. Left sural nerve biopsy revealed mild lymphohistiocytic inflammation with focal loss of large myelinated axons. He was diagnosed with inflammatory myositis based on clinical and histopathologic findings and started on 60 mg (1 mg/kg) of prednisone daily with 1 mg/kg of intravenous immunoglobulins (IVIG) in 2 divided doses. He was discharged on a prednisone taper with a plan to continue monthly IVIG infusions in an outpatient clinic at 2-month follow-up, he reported new rashes on the extensor surfaces of the hands consistent with Gottron’s papules, mechanic’s hands, and livedo reticularis of feet and arms. While there had been adequate recovery of muscle strength with treatment with corticosteroids and IVIG, cutaneous features of DM had emerged 2 months after starting treatment.

Table 1.

Pertinent Laboratory Investigation.

Laboratory investigation	Value (reference range)
ESR	91 mm/h (<30 mm/h)
CRP	201 mg/L (<5 mg/L)
CPK	27 U/L (<200 U/L)
Aldolase	16.5 U/L (<10.3 U/L)
Myositis-specific antibodies, anti-Jo-1, anti-Pl-7, anti-PL-12, anti-EJ, anti-OJ, anti-SRP, anti-MI-2, anti-TIF-1GAMMA, anti-MDA-5, anti-NXP, anti-SAE, anti-PM/SCL-100, anti-KU, anti-SS-A, anti-RNP, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	Negative

Abbreviations: ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; CPK, creatine phosphokinase.

Image 1.

Magnetic resonance imaging showing diffuse bilateral edema on cross-sectional view of femoral muscle, prominent in vastus laterials (T2 weighted images).

Discussion

Pathophysiology of DM is complex with activation of the complement system and formation of a membrane attack complex (MAC) in the vascular walls of skin and muscle. ² This leads to muscular degeneration, necrosis, and disruption of the skin dermis with characteristic findings (Gottron’s papules, heliotrope rash, facial erythema, shawl sign, poikiloderma, mechanic’s hands, and calcinosis cutis). ² Patients typically complain of difficulty with activities of daily living such as climbing stairs, sitting up from a chair, and combing hair. Clinical manifestations include classic DM, clinically amyopathic DM (CADM), and DM sine dermatitis. Clinically amyopathic DM presents without muscle involvement, ³ and DM sine dermatitis presents without skin rash. ⁴ Most commonly patients present with skin changes followed by muscle weakness; however, in our case, the lower extremity weakness preceded the typical skin findings. Moreover, this is the first reported case in the literature where the skin changes occurred after commencing immunosuppressive therapy and with complete improvement in muscle strength.

Laboratory evaluation aids in diagnosis and typically demonstrates elevated enzymes suggestive of muscle damage (creatine phosphokinase (CPK), aldolase) and/or positive myositis-specific and myositis-associated antibodies. ² Most common antibodies in DM are anti-MI-2, anti-MDA-5, anti-TIF-1GAMMA, anti-NXP, and anti-SAE antibodies. ⁵ Our patient had mildly elevated aldolase level with normal CPK and all myositis-specific antibodies negative at the time of presentation. This prompted further evaluation with EMG, MRI, and muscle biopsy. Electromyography helps differentiate IIM from neurological disease, typically showing fibrillation with activation of smaller muscle units, which was present in our patient. ¹ Magnetic resonance imaging of the affected muscle can demonstrate inflammatory changes, and cases of DM usually have diffuse patchy opacities throughout the muscle with or without subcutaneous edema. ⁶ Muscle and skin biopsy can help establish diagnosis; however, the pathohistological findings may be nonspecific as was the case in our patient. Nerve biopsy may be done to exclude other causes of muscle weakness; however, DM can be associated with peripheral neuropathy. ⁷ A previous report found that neuropathy and DM share a similar pathogenic mechanism of involvement with MAC formation and C5b-9 deposition in nerve fibers. ⁷

Based on the presenting symptoms, imaging, and pathohistology, our patient was diagnosed with nonspecific, seronegative inflammatory myositis and commenced on immunosuppressive treatment. First-line treatment for IIM and DM are corticosteroids. Starting dose is 1 to 1.5 mg/kg of prednisone daily, which is tapered down to a daily dose of 5 to 10 mg. ⁸ Manifestations usually resolve within 24 to 48 months of steroid taper. ⁹ However, in a certain number of cases, an additional steroid-sparing agent is needed—such as methotrexate, IVIG, cyclosporine, or mycophenolate mofetil.^8,9 Our patient presented with rapidly progressive symptoms which significantly affected his daily life and was commenced on both IVIG and steroid taper. He demonstrated complete recovery of muscle strength; however, skin changes occurred after 2 months of treatment, necessitating continuation of taper. If cutaneous manifestations remain refractory to treatment, a second steroid-sparing agent is often needed, and treatment with newer agents such as tofacitinib can be considered. ¹⁰

All patients, especially those presenting in the fifth-sixth decade of life with DM should be evaluated for underlying diseases and malignancies, including interstitial lung disease (ILD), ovarian, breast, lung, and colon cancer. Almost half of the patients with DM/PM develop ILD. ¹¹ Interstitial lung disease is associated with increased mortality in this patient population; however, it has also proven to be inversely associated with the risk of developing malignancy. ¹² The role of malignancy screening, based on DM as a risk factor, is controversial, and further studies are needed to determine the utility of routine screening in this patient population. ¹² Our patient was screened for ILD, esophageal, gastric, and colon cancer—all of which were negative. There was no underlying disease identified as a clear trigger. Mortality rate in DM is as high as 48%, with recent study reporting improved survival over the last decade.^13,14 Adequate classification of IIM is important, and it has been reported that DM has significantly higher mortality than PM, partially due to stronger association with underlying malignancies. ¹⁵

Conclusion

Our case is a unique presentation of DM in a middle-aged male patient who presented with no cutaneous involvement, absence of autoimmune-antibodies, normal CPK, and non-specific muscle biopsy. Skin changes developed after immunosuppressive therapy was started for idiopathic myositis and with recovery in muscle strength. Our case testifies to the unpredictable and variable nature of DM. Future long-term follow-up studies are necessary to better understand incidence of the late-onset development of typical skin findings.