Dermatomyositis Flare After a COVID-19 Infection Successfully Treated with Rituximab: A Case Report and Literature Review

Introduction

Dermatomyositis (DM) is a rare immune-mediated disease characterized by distinct dermatological features and proximal inflammatory myopathy.¹ The disease results from an amalgam of genetic predisposition and environmental factors that trigger an incompletely understood immune disturbance.^2,3 To date, it remains controversial whether the inflammatory cascade is initiated by complement fixation or antibody-dependent activation of interferon pathway.^3,4

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, a sudden surge in the incidence of DM was noted.^5–7 For instance, the rate of new cases of juvenile DM admitted in a tertiary care center in Iran from February 2020 to February 2021 was almost four times the rate of cases during the past full decade.⁶ Moreover, patients with DM were reported to have frequent relapses during the COVID-19 pandemic.⁸ In a large Italian cohort of 1641 patients with COVID-19-related autoimmune diseases, polymyositis and DM constituted approximately 1.2% of all the cases.⁹ Of 608 patients with COVID-19-related myositis reported via an online survey, DM was the most common type, occurring in 40.6% of the participants.¹⁰

The etiopathogenesis of the co-occurrence of DM and COVID-19 infection remains elusive. Clinical, laboratory and pathological similarities between the two diseases have been recognized.¹¹ Some cases of DM were reported to present with symptoms closely similar to that of COVID-19 pneumonia, such as the case reported by Mengke et al,¹² but the COVID-19 polymerase chain reaction (PCR) tests were repeatedly negative. A similar case of anti-malondialdehyde antibody-5 (MDA-5) DM was reported to present with interstitial lung disease (ILD) mimicking COVID pneumonia.^11,13 Both DM and COVID-19 infection have similar lab profiles (such as elevated C-reactive protein (CRP) and elevated ferritin) and similar lung radiological features (ie, ground glass opacifications and bronchovascular consolidation).¹¹ Evidence exists that suggests the presence of antibodies against immunogenic muscle epitopes in patients with COVID-19 infection.^7,14

The described cases of DM occurring in the context of COVID-19 infection are rare in the literature and heterogeneous. Their clinical features, laboratory findings, and treatments are inconsistent. Given the incomplete current understanding of the overall theme of co-occurrence of DM and COVID-19 infection, we aimed in this article to contribute to the literature with a new rare case of DM exacerbation after a COVID-19 infection.

Case Presentation

We report a 23-year-old female patient diagnosed with DM 3 years before her current presentation. The diagnosis was based on the clinical presentation of Gottron’s papules, heliotrope rash, inability to comb her hair, walk up the stairs, or stand from a sitting position (proximal myopathy), elevated creatinine kinase, and muscle biopsy. She has been well-controlled on maintenance therapy of methotrexate and oral prednisolone 5 mg daily. On July 15th, 2021, she presented with rhinorrhea, fever, and dry cough and was diagnosed with a COVID-19 mild infection. Her prednisolone dose was increased to 20 mg daily and then tapered over 4 weeks. The COVID-19 infection ultimately resolved on July 30, 2021.

Six weeks later, she presented with an exacerbation of DM symptoms in the form of re-appearance of Gottron’s papules on both hands, heliotrope rash, and generalized muscle weakness, Medical Research Council’s scale (MRC scale) grade 4/5, that impaired her activity of daily living (ADL). Her lab profile revealed aspartate aminotransferase (AST): 91 U/L, alanine aminotransferase (ALT): 255 U/L), elevated creatinine phosphokinase (CPK): 9052 U/L, leucocytosis: 12.04 cells/cc³, and elevated CRP: 4.45 mg/d. The patient received a dose of IVIG 1g/kg daily for 2 days, the prednisolone dose was increased to 10 mg daily, and methotrexate was continued. Nevertheless, the patient’s condition got worse in terms of the progression of her weakness and persistence of the heliotrope rash. She became bedbound with an overall MRC grade 2/5 of the muscles of the proximal upper and lower limbs. She reported no fever, weight loss, dyspnea, chest pain, or bulbar dysfunction. The CPK level increased to 24,135 U/L, and the AST and ALT increased to 883 and 201 U/L, respectively. The septic and malignancy workup was unremarkable.

Accordingly, she was admitted to our hospital and administered pulse methylprednisolone 1g/day for 3 days, followed by oral prednisolone 1mg/kg/day and IVIG 1g/kg daily for 2 days. Methotrexate was stopped and was replaced with rituximab. In about 10 days, the patient improved, ie, the power of the upper extremity muscles became MRC grade 5/5, the lower extremity muscles became 4/5, the CPK was reduced to 12,108 U/L, and the rash disappeared. The patient was discharged from the hospital on oral prednisolone 40 mg daily to be tapered gradually (5 mg every week) along with rituximab as maintenance therapy. Since then, her DM remained in remission.

Discussion

Our patient presented with a DM flare in the context of COVID-19 infection. The case, despite having a mild COVID-19 infection, developed a flare-up in the form of cutaneous manifestations and muscle weakness that was only responsive to pulse methylprednisolone, IVIG, and rituximab.

Reference to Relevant Literature

In the literature, several cases have been reported to occur in the context of COVID-19 infection or vaccination.^{5,10,12,15–22} Table 1 summarizes the clinical characteristics, laboratory and investigational findings, treatment received, outcome, and temporal relation of DM to the COVID-19 infection. Table 2 outlines the same in relation to DM flare post-COVID vaccination. Of the 13 cases reported, two patients had DM following COVID-19 vaccination.^20,21 Most of the reported cases had DM either during, shortly after, or up to 2 months following COVID-19.^{5,10,12,15–22} The case series reported by Gokhale et al⁵ were diagnosed with DM before COVID-19 infection, similar to the case we present in this review, and their disease was exacerbated shortly before or during the COVID-19 infection.⁵ The weakness in the 13 reported cases ranged from severe weakness MRC grade 1/5 to mild weakness MRC grade 4/5.^{5,10,12,15–22} Systemic manifestations included ILD,^19,22 polyarthritis,¹⁶ and cardiomyopathy.^16,21,22 In the vast majority of reported cases, pulse intravenous methylprednisolone and/or IVIG were used to treat DM exacerbation. In a few cases, the DM exacerbation improved on oral prednisolone along with immunosuppressants.^5,16,19,21 Similar to the case of our patient, the outcome of all reported cases in the literature was favorable.

Table 1 Summary of Case Reports in Literature: Dermatomyositis Flare in Relation to COVID-19 Infection

Table 2 Summary of Case Reports in Literature: Dermatomyositis Flare in Relation to COVID-19 Vaccination

Comparison to the Current Gold Standard of Care

The standard treatments of DM include oral or pulse corticosteroids with or without IVIG for acute flares and corticosteroids, methotrexate, azathioprine, cyclophosphamide, cyclosporine, and/or hydroxychloroquine as maintenance therapy.^23–25 In patients with severe or refractory symptoms, more potent immunosuppressive drugs should be offered, such as rituximab.²⁴

Relevant Hypothesis Generation

In the literature, it has been proposed that certain proteins and receptors, such as MDA-5, play a crucial role in the innate immunity defense mechanisms against viral infections, including COVID-19.⁵ These receptors are activated by viral ribonucleic acid (RNA).⁵ Once activated, they stimulate interferon I (INF-I) and subsequent production of proinflammatory cytokines such as interleukin (IL-6), IL-1β, IL-18, INF- γ, and tumor necrosis factor-alpha (TNF-α).²⁶ Then, the cytokine storm stimulates T helper cells and macrophages and precipitates a flare-up or initiation of several immune-mediated disorders, including dermatomyosistis.⁹ For DM in specific, six distinct epitopes were found to be highly identical to the COVID-19 virus.^7,14 This consolidates the involvement of the molecular mimicry mechanism in evaluating DM in the context of COVID-19 infection.

Implications of Clinical Practice

The patient we describe represents an addition to the few reported cases in the literature that can add to the still-growing knowledge of the association between DM and COVID-19 infection. Similar to the cases reported by Gokhale et al,⁵ our patient exacerbated following a COVID-19 infection. Treatment of exacerbation with increasing doses of oral prednisolone did not seem to be adequate in our patient, and pulse steroids were necessitated. Clinicians should inquire about any history of COVID-19 infection, even if mild, in all patients with DM presenting with a flare-up of their symptoms. If COVID-19 was suspected of triggering the flare, clinicians should consider aggressive treatment of the DM exacerbation with pulse intravenous steroids, IVIG, and/or rituximab.

Strength and Limitations

The strength of this report is being one of the rare cases of COVID-19-related DM in the literature that can help understand and draw the full but still unclear picture of the actual relationship between the two disease entities, including the clinical presentation, lab tests, treatment, and prognosis. The main limitation is the relatively short-term follow-up of the case.

Conclusion

Dermatomyositis can occur within the context of COVID-19 infection either for the first time or as an exacerbation of a previously diagnosed disease. The prognosis is generally favorable. Clinicians should consider aggressive treatment of DM exacerbations post-COVID, with pulse intravenous steroids, IVIG, and/or rituximab. The use of rituximab should be based on the physician’s own clinical judgment.