Respiratory failure in dermatomyositis induced by anti-Mi-2β antibodies: case report

Introduction

Rheumatic pathologies account for a small percentage of respiratory-related deaths (1). Dermatomyositis is an idiopathic inflammatory myopathy that may manifest with progressive muscle weakness, skin abnormalities, elevated creatine kinase (CK), serum autoantibodies, and inflammatory infiltrates in muscle biopsy. Dermatomyositis is characterized by a distinctive skin rash and can involve extramuscular areas. The root cause is autoimmune destruction of muscle fibers and endomysial capillaries (2).

Pulmonary involvement is the most common extramuscular manifestation of idiopathic inflammatory myopathies. The main antibodies associated with dermatomyositis are anti-Mi-2, anti-MDA-5, anti-NXP-2, anti-TIF-1γ, and anti-SAE-1/2. Additionally, eight antisynthetase autoantibodies (ASAs) have been defined, which in some cases can mimic characteristics of dermatomyositis. These antibodies are: anti-Jo-1, anti-PL-12, anti-PL-7, anti-EJ, anti-OJ, anti-KS, anti-Zo, and anti-Ha/YRS (3). Dermatomyositis has been associated with more than 20 distinct antibodies. Although some variants progress rapidly and are associated with interstitial pulmonary involvement, such as those associated with myositis-specific autoantibodies, the anti-signal recognition particle, and anti-topoisomerase I. The anti-Mi-2β antibodies are associated with a subset of dermatomyositis characterized by low frequency of interstitial lung disease and malignancy, good response to treatment, and favorable outcome. The ten-year mortality rate of this variant is less than 5% (4).

Some patients may experience rapidly progressive hypoxemia and overlapping patterns of potentially life-threatening acute lung injury. The case of a 54-year-old female admitted to an Intensive Care Unit (ICU) in November 2023 is presented. She was diagnosed with dermatomyositis in August 2023 through a biopsy of the right lateral vastus muscle, which revealed an inflammatory infiltrate in the perimysium composed of lymphocytes and plasma cells with edema and focal areas of myocyte necrosis. Electromyography (EMG) was consistent with acute-phase dermatomyositis. The patient received immunosuppressive therapy. However, due to the refusal to accept invasive mechanical ventilation, the patient passed away on the fifth day of initiating immunosuppressive therapy. We present this case in accordance with the CARE reporting checklist (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-15/rc).

Case presentation

A 54-year-old female with a history of hypothyroidism and dermatomyositis was admitted to the hospital due to a clinical picture of one month’s evolution characterized by a decrease in functional class, dyspnea, non-productive cough, myalgias, facial erythema, and cutaneous rashes. During the clinical examination, symmetric Gottron’s papules were documented on the dorsal region of the metacarpophalangeal and interphalangeal joints, accompanied by “irregular” cuticles, telangiectasias, and subcutaneous calcifications (Figure 1).

Figure 1 Typical Cutaneous manifestations in dermatomyositis. (A) Heliotrope erythema. (B,D,E) Cutaneous calcinosis. (C) Symmetric Gottron’s papules on the dorsal region of the metacarpophalangeal and interphalangeal joints associated with “irregular” cuticles, accompanied by telangiectasias and subcutaneous calcifications. These images are published with the patient’s consent.

In the emergency department, there are no signs of circulatory failure. Oxygen saturation levels are at 82%, responding to supplemental oxygen via nasal cannula. Arterial blood gases indicate a mild oxygenation disorder with an arterial oxygen partial pressure (PaO₂)/fractional inspired oxygen (FiO₂) ratio of 275, with no acid-base balance disturbances. Admission levels of creatine phosphokinase (CPK) are 952 mcg/L, and lactate dehydrogenase (LDH) is 365 IU/L. The blood count reveals a normocytic normochromic grade II anemia (hemoglobin: 9.5 g/dL, hematocrit: 31.2%, mean corpuscular volume: 92 fL, mean corpuscular hemoglobin: 33 g/dL). There is no evidence of leukocytosis, neutrophilia, fever spikes, or an increase in procalcitonin levels.

The patient reveals having discontinued the immunosuppressive treatment with prednisolone and methotrexate on her own accord. Two months prior, she was hospitalized for the administration of cyclophosphamide. A chest CT angiography is performed to rule out pulmonary embolism, documenting a small filling defect in the left lower lobe artery at the peripheral level, which could be related to chronic pulmonary embolism. Bilateral basal atelectasis, predominantly on the left, is observed without signs of superinfection, along with diffuse increased density in a ground-glass opacification pattern suggestive of a congestive appearance.

Anticoagulation was initiated with enoxaparin. Considering autoimmune pathology activity and after ruling out an overlapping infectious component with the evaluation by infectious disease specialists, treatment with intravenous cyclophosphamide was initiated, along with pulses of intravenous methylprednisolone at 500 mg daily for five days. In the following days, the patient experienced a reduction in symptoms and improvement in oxygenation parameters, achieving an increase in the PaO₂/FiO₂ to 314. However, upon completing the pulses of methylprednisolone, she developed worsening respiratory patterns, productive cough, febrile episodes, and required a FiO₂ of 50% to maintain borderline SaO₂ levels.

At the onset of respiratory failure, arterial blood gases reveal severe oxygenation impairment with a PaO₂/FiO₂ of 108 associated with metabolic alkalosis [pH 7.53, partial pressure of carbon dioxide (PCO₂) 32 mmHg, partial pressure of oxygen (PO₂) 52 mmHg, HCO₃ 27 mEq/L]. A follow-up chest computed tomography (CT) shows consolidation with a pneumonic appearance in the left lower lobe of the lung with atelectatic phenomena in both lung bases (Figure 2). The BLUE protocol is implemented, documenting widespread B-lines. In the presence of hypotension [mean arterial pressure (MAP) 52 mmHg], tachypnea [respiratory rate of 38 breaths per minute (BPM)], and tachycardia (heart rate 127 BPM), pulmonary-origin septic shock is considered, and antibiotic therapy with piperacillin-tazobactam and norepinephrine at 0.1 mcg/kg/min were initiated.

Figure 2 Imaging studies of the patient. (A) Chest CT angiography displaying bilateral basal atelectasis, predominantly on the left. Slight diffuse increase in density in a ground-glass opacification pattern. (B) Chest X-ray revealing blurring of the left costophrenic and cardio-phrenic angles, suggestive of either pleural effusion or pleural thickening. Bilateral basal ground-glass opacities may correspond to a consolidative process. CT, computed tomography.

The patient declined orotracheal intubation for 24 hours. After 36 hours of severe respiratory failure, the patient agreed to invasive mechanical ventilation. She was transferred to the ICU and unfortunately succumbed to the condition eight hours after admission.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Dermatomyositis is an idiopathic inflammatory condition characterized by chronic inflammation of the skin and muscles. Muscular involvement typically presents as symmetric proximal muscle weakness, with or without myalgias. Like our patient, a skin rash often appears before or during muscle weakness, and its manifestations can be quite variable, affecting the skin around the eyes or over the knuckles, and may involve cutaneous calcinosis (2).

Since its original description in 1956, its association with interstitial lung disease has been recognized (5). The most common extramuscular manifestation of dermatomyositis is pulmonary involvement, with nonspecific interstitial pneumonia being the most common form. Some patients, such as the one presented, experience rapidly progressive hypoxemia and show overlapping patterns of acute lung injury. Pleuritis, bronchiolitis, and vascular changes are uncommon in myositis. A recent cohort study involving 1,374 newly diagnosed myositis patients concluded that patients with dermatomyositis had a five-fold increased risk of respiratory failure (6). A retrospective investigation of 102 patients admitted to the ICU with polymyositis and dermatomyositis reported that the most common reasons for admission were isolated infection (39.2%), isolated acute exacerbation of the disease (27.5%), and a combination of both (27.5%). Pneumonia accounted for 97% of infections, with opportunistic organisms posing a feared complication. Additionally, rapidly progressive interstitial lung disease was responsible for 87.5% of acute exacerbations, and acute respiratory failure was the most common type of organ failure with a mortality rate of 79.4%. Patients with dermatomyositis may experience aspiration pneumonia due to dysphagia, ventilatory failure secondary to muscle weakness, primary or metastatic malignant neoplasms, pleural effusion, or spontaneous pneumothorax. The progression of respiratory complications can lead to challenging respiratory failure management, as seen in the case of our patient (7).

One of the most lethal and extensively lung-involved forms of dermatomyositis is associated with the presence of anti-MDA5 antibodies. This subtype of the disease was initially identified in Japanese patients with dermatomyositis who presented with little or no evident muscle weakness but with a rapid deterioration of lung function threatening life. Over time, it has been observed that this clinical phenotype can manifest with a wide range of additional symptoms, including cutaneous, articular, and vascular manifestations. Based on the predominance of these symptoms, three distinct clinical subtypes have been defined, each with its own prognosis. To date, the only common molecular component among these subtypes is the presence of antibodies specifically targeting MDA5, a crucial cytosolic protein in the host’s antiviral immune responses. In our clinical case, we encountered a patient whose analyses showed the absence of anti-MDA5 antibodies; however, her clinical course was exceptionally severe. Despite being diagnosed with anti-Mi-2β dermatomyositis, a form of dermatomyositis associated with a favorable long-term prognosis and optimal response to treatment, she experienced rapid respiratory deterioration leading to rapidly progressive and fatal interstitial lung disease in a short period of time. Despite receiving treatment with immunotherapy and broad-spectrum antibiotic coverage to address potential secondary infections, unfortunately, the deterioration was fulminant, culminating in the patient’s death (8).

Radiologically, dermatomyositis is characterized by a high incidence of airspace consolidations, a low incidence of honeycombing, the presence of atelectasis, and linear and ground-glass opacities, as observed in our case. Some patients may exhibit parenchymal micronodules. The most striking radiological finding in our report is the rapid development of airspace consolidation, correlating with an acute clinical presentation described in other reports (9).

Patients diagnosed with dermatomyositis may exhibit elevated levels of muscle enzymes in serum [CK, aspartate aminotransferase (AST), alanine aminotransferase (ALT), LDH, and aldolase] and acute-phase reactants such as C-reactive protein. They may have specific antibodies such as anti-Jo-1, anti-SRP, and anti-Mi-2, as well as associated antibodies like anti-Ro, anti-La, anti-U1-RNP, anti-U2-RNP, anti-Ku, anti-Sm, anti-PM/Scl. EMG reveals signs of primary muscle damage, and muscle biopsy demonstrates the presence of inflammatory infiltrates, primarily composed of lymphocytes. Diagnosis is established based on clinical symptoms and signs, particularly muscle weakness and the presence of characteristic skin lesions, in association with the results of muscle histological examination and EMG (10).

Immunosuppressive treatment, supportive therapy, and mechanical ventilation are crucial in managing respiratory failure induced by dermatomyositis. A comprehensive review of immunosuppression in the ICU is beyond the scope of this case report. Some alternatives include the use of intravenous methylprednisolone at 0.5–1.0 g for 3 days followed by prednisolone at 1 mg/kg/d. After the normalization of muscle damage markers and increased muscle strength, but not before 4–8 weeks from the start of treatment, the daily dose of oral glucocorticoid should be gradually reduced to achieve a maintenance dose of 5–10 mg/d, and treatment should be continued for several years, sometimes lifelong.

If the disease course is rapid or accompanied by respiratory failure, methotrexate (10–15 mg per week) with folic or folinic acid, azathioprine (1.5–2 mg/kg/d; reducing the dose every month to a maintenance dose of 50 mg/d), cyclosporine (2.5–5 mg/kg/d), cyclophosphamide (1.0 g intravenous per month), or intravenous nonspecific human immunoglobulin (0.4 g/kg/d for 5 consecutive days per month, for 3–7 consecutive months), rituximab, tacrolimus, and anti-TNF drugs can be added to the treatment regimen. In cases of refractory severe respiratory failure, the utility of extracorporeal membrane oxygenation (ECMO) has been considered (11,12).

Conclusions

This case report highlights the lethality of pulmonary complications resulting from dermatomyositis. Patients with dermatomyositis face an increased risk of respiratory failure, and when associated with superinfections, the mortality rate approaches 100%. Those undergoing steroid treatment are more susceptible to complications. Early diagnosis, mechanical ventilation, and corticosteroids constitute the cornerstone in managing dermatomyositis-induced respiratory failure. Despite being an atypical presentation, dermatomyositis associated with anti-Mi-2 can also manifest as a rapidly progressive and potentially lethal interstitial lung disease. Although the typical pattern of anti-Mi-2 dermatomyositis is characterized by a favorable clinical course and an optimal response to treatment, in some patients, it can have a fatal outcome. The reason for this is still unknown, which warrants further studies to comprehend the genotypic and phenotypic relationship of the less severe variants of dermatomyositis.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-15/rc

Peer Review File: Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-15/prf

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-15/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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