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CASE REPORT Table of Contents  
Ahead of print publication
Multisystem inflammatory syndrome in adults: Underdiagnosed??

 Department of General Medicine, Mallige Medical Centre, Bengaluru, Karnataka, India

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Date of Submission14-Jul-2021
Date of Decision30-Jul-2021
Date of Acceptance04-Aug-2021
Date of Web Publication23-Feb-2022


Multisystem inflammatory syndrome (MIS) in adults is a rare diagnosis compared to its counterpart in children. There are standard guidelines for the managment of MIS in children, the lack of such standard guideline for adult patients makes it a diagnostic challenge. Furthermore, lack of awareness about MIS-A among treating doctors can result in the condition to go undiagnosed or misdiagnosed. Here, we are presenting a rare case of MIS in a 38-year-old female who presented to us with a history of fever and cervical lymphadenopathy.

Keywords: COVID-19 infection, inflammatory markers, intravenous immunoglobulin, multisystem inflammatory syndrome in adults

How to cite this URL:
Ravindra T S, Yeldo D, Arjun B S. Multisystem inflammatory syndrome in adults: Underdiagnosed??. APIK J Int Med [Epub ahead of print] [cited 2022 Oct 6]. Available from: https://www.ajim.in/preprintarticle.asp?id=338151

  Introduction Top

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has led to a multitude of clinical presentations, ranging from olfactory dysfunction, COVID pneumonia, to so-called COVID toes, leading to a constant change of what we understood as the spectrum of illness. Multisystem inflammatory syndrome in children (MIS-C) is a serious condition that appears in children which is linked to COVID-19 infection. MIS-C is a rare complication occurring in children which is recognized officially by the WHO and the Government of India and standardized treatment guidelines is published by the said organizations. In contrast to this, MIS-A is very rare and the parallel syndrome in adults has not been well defined. The research data on MIS-A are very limited, and here, we are presenting a 38-year-old female whom we diagnosed with MIS-A and how we treated her.

  Case Report Top

A 38-year-old female, with no known medical comorbidities, came to our hospital with complaints of fever for 3 days and pain over the left side of the neck for 3 days. She gave a history of COVID-19 infection 45 days back and was home quarantined for 2 weeks. Her last menstrual period was 10 days back and had dysmenorrhea.

On examinations, vitals were stable and local examination showed enlarged left cervical lymph nodes. Initial blood investigations showed normal parameters except mild hypophosphatemia. Her hemoglobin level was 13.6 g/dl, total count of 10160 cells/cumm, and a platelet count of 2.07 lakhs/cumm. ENT consultation was sought in view of neck pain and lymph node fine-needle aspiration cytology was done which revealed reactive lymphadenitis [Figure 1],[Figure 2]. She was started on intravenous (IV) antibiotics (IV Ceftriaxone) and other supportive medications. After 2 days of admission, the patient developed tachycardia, hypotension, and she had a persistent fever. The patient was shifted to intensive care unit (ICU) and was started on inotrope support. Her oxygen saturation was always > 95% and she did not have breathlessness at any point during her hospital stay.
Figure 1: Cervical lymph node cytology

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Figure 2: Lymph node cytology showing polymorphous proliferation

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Repeat blood investigations showed neutrophilic leukocytosis and raised inflammatory markers including serum procalcitonin (44.1 ng/ml), D-dimer (791 ng/ml), C-reactive protein (CRP) (249.7 mg/L). Her trop T level was 51.52 pg/ml (Normal- 0–14 pg/ml), creatine phosphokinase-MB level was 1.71 ng/ml (normal- 0–2.88 ng/ml), and NT-Pro BNP level was 7045 pg/ml (normal 0–125 pg/ml). Opinion of cardiologist was taken and two-dimensional ECHO was done which showed normal left ventricular (LV) function with ejection fraction- 55%–60% and no evidence of infective endocarditis.

Anti-SARS COVID antibody was positive (117 U/ml). COVID-19 real-time reverse transcription-polymerase test was negative. Dengue serology, typhidot immunoglobulin M, Weil-Felix, leptospira antibody, brucella test, and Paul–Bunnell test were sent which were all negative. Blood and urine culture showed no growth. Chest X-ray was normal and ultrasonography of the abdomen and pelvis showed no abnormalities.

A clinical diagnosis of MIS-Adults (MIS-A) was made and the patient was started on IV immunoglobulin (IVIG), steroids, and low-molecular weight heparin. IVIG was given at a dose of 2 g/kg in divided doses over 48 h. Repeat investigations after IVIG treatment showed decrease in leukocyte count to normal levels and hypokalemia. Inflammatory markers levels were also decreased: serum procalcitonin (0.61 ng/ml), D-dimer (1162 ng/ml), and CRP level (19.82 mg/L). Clinically, patients' fever subsided and inotrope support was stopped. The patient was shifted to ward from ICU and monitored. Gynecology opinion was taken in view of dysmenorrhea and Pap smear was done which was negative for intraepithelial lesions and malignancy. At the time of discharge, the patient was asymptomatic and all investigations including inflammatory markers were within normal limits.

  Discussion Top

A post COVID-19 multisystem inflammatory syndrome (MIS) has been recognized as a rare, yet severe, complication of SARS-CoV-2 infection. First and mainly recognized in children,[1],[2] MIS in adults is now being reported[3],[4] and further awareness and insights into this emerging syndrome are required. As MIS-A continues to challenge physicians, early intervention with SARS-CoV-2 testing, including antibody testing might be needed to recognize and treat patients.

Following infection, adults with acute COVID-19 often experience fever accompanied by respiratory symptoms. A minority of patients experience persistent and worsening symptoms, usually dyspnea warranting hospital admission. A small proportion of patients progress to a later stage of COVID-19, at times referred to as the cytokine storm. This is the third and most severe stage of the COVID-19 illness (1–4 weeks), which manifests as a systemic hyperinflammation syndrome characterized by increase in inflammatory markers. In contrast, a very small proportion of the patients sought hospital care usually within 84 days (4–12 weeks) post COVID having fever, abdominal pain, nausea, vomiting, varied mucocutaneous findings, and often symptoms indicative of myocardial dysfunction accompanied by severe inflammation. These findings are suggestive of MIS-A and our case fits into this criterion.


  • Centers for disease control and prevention have devised a criterion for diagnosing MIS-A
  • Case definition for MIS-A.[5]

A patient aged ≥21 years hospitalized for ≥24 h, 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 (e.g., bacterial sepsis, exacerbation of a chronic medical condition).

Clinical criteria

Subjective fever or documented fever (≥38.0 C) for ≥24 h prior to hospitalization or within the first 3 days of hospitalization* and at least three of the following clinical criteria occurring prior to hospitalization or within the first 3 days of hospitalization*. At least ONE must be a primary clinical criterion.

  1. Primary clinical criteria

    1. Severe cardiac illness includes myocarditis, pericarditis, coronary artery dilatation/aneurysm, or new-onset right or LV dysfunction (LV ejection fraction <50%), 2nd/3rd degree A-V block, or ventricular tachycardia (Note: cardiac arrest alone does not meet this criterion)
    2. Rash AND nonpurulent conjunctivitis

  2. Secondary clinical criteria

  1. New-onset neurologic signs and symptoms include encephalopathy in a patient without prior cognitive impairment, seizures, meningeal signs, or peripheral neuropathy (including Guillain-Barré syndrome)
  2. Shock or hypotension not attributable to medical therapy (e.g., sedation, renal replacement therapy)
  3. Abdominal pain, vomiting, or diarrhea
  4. Thrombocytopenia (platelet count <150,000/μl).

Laboratory evidence

The presence of laboratory evidence of inflammation AND SARS-CoV-2 infection.

  1. Elevated levels of at least two of the following: CRP, ferritin, IL-6, erythrocyte sedimentation rate, procalcitonin
  2. A positive SARS-CoV-2 test during the current illness by RT-PCR, serology, or antigen detection

Note: *These criteria must be met by the end of hospital day 3, where the date of hospital admission is hospital day 0.


Ministry of Health and Family Welfare, India, has published guidelines for the management of MIS in children which they suggested IVIG 2 g/kg over 24–48 h which was followed in our case.[6]

Several features of MIS-A require urgent attention. First, a lack of clear guidance regarding diagnosis highlights the need to establish MIS-A case definitions and testing algorithms. Although antibody testing is strongly recommended by the Infectious Diseases Society of America in the setting of MIS-C,[7] the role of antibody testing for cases of suspected MIS-A needs to be defined. Second, optimal treatment is unclear at this time and will likely require evidence outside of randomized controlled trials given the rarity of this syndrome. IV immunoglobulin, steroids, and other immunomodulatory agents have been used to treat suspected cases of MIS-A, with clinical improvement noted in some instances. Third, the potential for chronic sequelae in affected patients is not yet known and could affect long-term follow-up care and monitoring, such as repeat echocardiography. Finally, further studies on the immunopathogenesis of this syndrome are needed. If MIS is postinfectious or antibody-mediated, there could be important implications for vaccine safety.

  Conclusion Top

Multisystem inflammatory syndrome in adults should be kept in mind as a differential diagnosis in patients with age more than 21 years with unexplained rise in inflammatory markers including serum procalcitonin and had a history of COVID-19 infection. This is very crucial as we had an inherent reflex to jump to a conclusion of sepsis as soon as we saw raised serum procalcitonin. Furthermore, the lack of awareness about the condition in adults makes it a diagnostic nightmare. The Center for Disease Control and Prevention (USA) has put forth a criteria which can be referenced if we come across a suspected patient. The treatment with IV Immunoglobulin shows dramatic improvement and should be the first line of treatment in MIS-A.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that her name and initial will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, MPH, Son MB, et al. Overcoming COVID-19 investigators; CDC COVID-19 response team. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med 2020;383:334-6. [doi: 10.1056/NEJMoa2021680].  Back to cited text no. 1
Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020;383:347-58.  Back to cited text no. 2
Chau VQ, Giustino G, Mahmood K, Oliveros E, Neibart E, Oloomi M, et al. Cardiogenic shock and hyperinflammatory syndrome in young males with COVID-19. Circ Heart Fail 2020;13:e007485.  Back to cited text no. 3
Morris SB, Schwartz NG, Patel P, Abbo L, Beauchamps L, Balan S, et al. Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection - United Kingdom and United States, March-August 2020. MMWR Morb Mortal Wkly Rep. 2020 Oct 9;69(40):1450-1456. doi: 10.15585/mmwr.mm6940e1. PMID: 33031361; PMCID: PMC7561225.  Back to cited text no. 4
Centers for Disease Control and Prevention. Multisystem Inflammatory Syndrome (MIS). Centers for Disease Control and Prevention. 2021. Available from: https://www.cdc.gov/mis/mis-a/hcp.html. [Last cited on 2021 May 11].  Back to cited text no. 5
Guidelines for Management of COVID-19 in Children (below 18 years). Ministry of Health & Family Welfare Government of India; 2021. Available from: https://www.mohfw.gov.in/pdf/GuidelinesforManagementofCOVID19inCHILDREN18June2021final.pdf. [Last cited on 2021 Jun 18].  Back to cited text no. 6
Hanson KE, Caliendo AM, Arias CA, Englund JA, Hayden MK, Lee MJ, et al. Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19:Serologic Testing. Clin Infect Dis. 2020 Sep 12:ciaa1343. doi: 10.1093/cid/ciaa1343. Epub ahead of print. PMID: 32918466; PMCID: PMC7543294. Page Number: 41.  Back to cited text no. 7

Correspondence Address:
Dilmo Yeldo,
Department of General Medicine, Mallige Medical Centre, 31/32 Crescent Road, Madhava Nagar, Gandhi Nagar, Bengaluru - 560 001, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajim.ajim_72_21


  [Figure 1], [Figure 2]


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