Multisystem inflammatory syndrome in adults (MIS‐A): a new addition to COVID‐19 puzzle

The novel coronavirus (SARS-CoV-2) has crippled the world by its fatality and protean manifestations, of which multisystem inflammatory syndrome seems to be a relatively new trick under its sleeve. A myriad of dermatological manifestations with incompletely understood pathophysiology such as maculopapular rash, erythema multiforme-like lesions, vesicular and urticarial lesions, chilblains, livedo reticularis-like lesions have been reported in COVID-19.1 A 24-year-old male presented with a high-grade fever for 8 days accompanied by a subacute onset progressive holocranial headache, vomiting, malaise a day later followed by a generalized maculopapular rash, which appeared on the 5th day of fever, initially on his right arm and then gradually involved all the limbs and trunk. Three weeks back, he had close contact with a confirmed case of COVID-19. On examination, the patient was febrile and pale with mild conjunctival congestion, suggestive of non-purulent conjunctivitis (Fig. 1; Panel a). Apart from meningism, his systemic examination was unremarkable. Dermatological examination revealed a non-pruritic, non-scaly, blanchable maculopapular rash which assumed a dusky, plaque-like morphology after 5 days. (Fig. 1; Panel b, c, d). Relevant laboratory investigations revealed normocytic, normochromic anaemia with transaminitis. Malaria, dengue, leptospirosis, scrub typhus were ruled out with supportive investigations; blood and urine culture did not reveal any growth. Reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2 was also negative. His coagulation profile was normal, and inflammatory markers were elevated. Chest, abdominal imaging, transthoracic echocardiography and brain imaging (contrast-enhanced MRI brain and MR venogram) were non-contributory. A guarded lumbar puncture revealed a mildly elevated opening pressure, lymphocytic pleocytosis and mildly elevated protein level and a negative neuroviral panel. Serum anti-SARS-CoV-2 S antibody was elevated with a value of 16 (reference range < 1.40). As per the clinical criteria of multisystem inflammatory syndrome in adults (MIS-A) formulated by the Centres for Disease Control and Prevention (CDC), the patient satisfied one primary and two secondary criteria, based on which he was diagnosed as a case of MIS-A. He was initiated on pulse intravenous methyl-prednisolone (1gram/day for 5 days) and relevant symptomatic management which led to dramatic improvement in his symptoms and an uneventful recovery. Multisystem inflammatory syndrome in children (MIS-C) predominantly manifesting as shock, cardiovascular abnormalities, pain abdomen with markedly elevated inflammatory markers is a relatively new entity reported worldwide in association with COVID-19. It tends to mimic Kawasaki disease as they present with polymorphic, erythematous rash, mucosal involvement in the form of conjunctivitis and mucositis, erythema and firm induration of limbs.2 Several reports of a similar syndrome in adults with cardiovascular, gastrointestinal, dermatologic and neurologic symptoms without severe respiratory illness have concurrently received attention around the globe. These patients have either tested positive for SARS-CoV-2 by polymerase chain reaction (PCR) or they had positive antibody assays indicating recent infection. Considering the heterogeneity of presenting symptoms, CDC has formulated the case definition for MIS-A (Table 1). Negative PCR and positive antibodies suggest that MIS-A/MIS-C are postinfectious entities.3 Although multisystem inflammatory state in moderate-to-severe COVID-19 is generally accompanied by respiratory failure, there has been a paucity of respiratory symptoms, hypoxaemia or radiographic abnormalities in MIS-A.4 The pathophysiology of MIS-A though debated includes dysregulation of immune responses, dysfunction of renin-angiotensin-aldosterone axis, endothelial injury and thromboinflammation.5 The distribution of rash was generalized in majority of MIS-C, although only palm and sole erythema were present along with desquamation of the digits in some. Conjunctivitis and cheilitis with variable pruritic and painful rash have also been reported. Dermatological manifestations of MIS-A are grossly underreported with reports of mucositis, polymorphic rash, acral or facial swelling, erythema multiforme-like lesions, palmoplantar desquamation, erythroderma in the literature. The optimal treatment of MIS-A is unclear, although intravenous immunoglobulin, steroids and other immunomodulatory agents have been used with clinical improvement in some instances.6 Moreover, the chronic sequelae and the long-term consequences in terms of morbidity and mortality in affected patients are yet to be understood, and better understanding of the immunopathogenesis warrants further research. Case definition for MIS-A: A patient aged ≥21 years hospitalized for ≥24 hours or with an illness resulting in death, who meets the following clinical and laboratory criteria. The patient should not have a more likely alternative diagnosis for the illness (eg, bacterial sepsis, exacerbation of a chronic medical condition). Subjective fever or documented fever (2':38.0 C) for 2':24 h prior to hospitalization or within the first THREE days of hospitalization* and at least THREE of the following clinical criteria occurring prior to hospitalization or within the first THREE days of hospitalization*. Primary clinical criteria 1. Severe cardiac illness includes myocarditis, pericarditis, coronary artery dilatation/aneurysm or new-onset right or left ventricular dysfunction (LVEF < 50%), 2nd/3rd degree A-V block or ventricular tachycardia. (Note: cardiac arrest alone does not meet this criterion) 2. Rash and non-purulent conjunctivitis Secondary clinical criteria 1. New-onset neurologic signs and symptoms Includes encephalopathy in a patient without prior cognitive impairment, seizures, meningeal signs or peripheral neuropathy (including Guillain-Barre syndrome) 2. Shock or hypotension not attributable to medical therapy (eg, sedation, renal replacement therapy) 3. Abdominal pain, vomiting or diarrhea 4. Thrombocytopenia (platelet count < 150 000/ microliter) The presence of laboratory evidence of inflammation and SARS-CoV-2 infection. A. Elevated levels of at least TWO of the following: C-reactive protein, ferritin, IL-6, erythrocyte sedimentation rate, procalcitonin B. A positive SARS-CoV-2 test during the current illness by RT-PCR, serology, antigen detection None. Informed written consent obtained from the patient to publish the case details. None declared. Data sharing is not applicable to this article as no new data were created or analysed in this study.