CME INDIA Case Presentation by Dr Anand Malani, MD & Dr Sanjay Kulkarni, MS, Sangli, Maharashtra.

CME INDIA Case Study

When diagnosis was like Pandora’s Box.

“It is said that when Pandora disobeyed the orders from Zeus and opened the box, all manner of dark and malicious things escaped, but Hope remained safely inside.”

How Presented?

• Since last 4-5 days.
• He also complained of mild to moderate grade fever.
• No history of chills or rigors, body ache, headache, any respiratory complaints or urinary complaints.
• He had not moved his bowel since last 3-4 days.
• The past history was insignificant for any medical or surgical problem. There was no history of COVID-19 in the recent past.

On Examination

• His vital parameters were normal, temperature was 100-degree F and oxygen saturation was normal.
• His systemic examination revealed mild tenderness in the right iliac fossa, other systems being normal. His routine investigations were ordered and so was abdominal ultrasound.

Lab Work up

• Ultrasound Abdomen: Thickening of ileo-caecal junction and ascending colon.
• Basic blood investigations: Pancytopenia with a white cell count of 1800/cu mm and platelet count of 35000/cu mm. His peripheral smear did not reveal any abnormal cells or leukocytes. His RFT was normal and LFT was deranged. He was further evaluated with CT scan of abdomen and further tests for pancytopenia with dengue test and others.
• CT abdomen: Small bowel obstruction with thickening of the ileocecal junction and ascending colon. Mesenteric and paraaortic lymphadenopathy was noted, the largest node being about 1.5 x 2 cm. Mild hepatosplenomegaly and ascites were also noted which was clear. The lung bases visualized in the CT scan did not reveal any abnormality.
• He was negative for HIV, Australia antigen, Hepatitis C, Dengue, Typhoid, Brucella.
• Leptospirosis IGM was positive.
• His COVID RT PCR done as a routine was negative.

What it looks like

• A case of young male presenting with acute febrile illness with intestinal obstruction with pancytopenia with hepatosplenomegaly and mild ascites and positive Leptospira serology.
• Certainly, we could not explain all his features on the basis of one disease or pathology.
• Abdominal TB with bone marrow and hepatic involvement was high on cards but the history was too short for the same.

Management

• He was treated with conservative management for intestinal obstruction with patient being kept NBM, and administered antibiotics CEFTRIAXONE and METROGYL which would cover the common organisms and Leptospira as well along with IV fluids.
• Surgical option was kept ready while further evaluation for pancytopenia was planned and bone marrow aspiration was under consideration.
• Patient responded to conservative management of small bowel obstruction within 2 days. His vomiting reduced, pain reduced and started passing loose motions. He was started on soft diet and oral DOXYCYCLINE.
• His blood counts were monitored daily for next few days which did not show any improvement. He kept on passing loose motions and running mild to moderate fever. His stool examination revealed occult blood 3+ and few pus cells favoring enterocolitis.

Twist in the Case

• At this stage along with CBC we ordered his CRP to assess severity of infection. His CRP was found to be 175 mg/dL which was quite disproportional to his clinical condition and severity of infection.
• So, we ordered other inflammatory markers namely LDH, Ferritin, D-dimer.
• To our surprise, his D-dimer was more than 10000 ng per ml, LDH was in thousands and so was his ferritin level.
•  His prothrombin time and APTT were within normal limits. Patient did not bleed anytime during the course of illness.

So, what happened next?

• A diagnosis of Macrophage activation syndrome was considered which is usually a severe disease, the patients being very sick and running a rapid downhill course unless treated aggressively. There was no history of any autoimmune or rheumatic disease on the background.
• The closest mimic although in a milder form could be MIS-C. As he was 21 years of age and there was no history of COVID this diagnosis was not considered at the outset. Just to ascertain we ordered his COVID antibodies IgG and IgM.
• To our surprise they were strongly positive. We again confirmed from the patient and his relatives that he did not suffer from COVID or COVID like symptoms in last few weeks to months, and nor did any family member or close contact.
• On further evaluation his ECHO revealed mild LV dysfunction with EF of 45% and TROP I was also POSITIVE favoring MYOCARDITIS.

Diagnosis

At this point a diagnosis of post-Covid mis-a [multisystem inflammatory syndrome-adult] was confirmed.

Now Management Modified

• Patient was started with high dose DEXAMETHASONE.
• Aspirin and anticoagulation were avoided as his platelet count was under 40000.
• Patient responded very well to the treatment with all his symptoms improving within 48 hours.
• His counts normalized and inflammatory markers decreased by almost 70% within 48 hours. ASPIRIN and RIVAROXABAN were started after platelet count went above 1 lakh/cu mm.
• Need to mention here that the Leptospira IgM was false positive.

Final Diagnosis:

Multi system inflammatory syndrome-adult post asymptomatic covid-19 infection, presenting with acute intestinal obstruction and involvement of haematological, cardiovascular, hepatic and gastro intenstinal systems.

CME INDIA Take Home Message

• MIS-A is now a known clinical entity just like MIS-C. The criteria are defined by various medical societies. It is usually seen after moderate to severe COVID-19 infection.
• It is common in children where it is called as MIS-C and rare in adults called as MIS-A and may be rarer after asymptomatic COVID-19 infection.
• It needs aggressive treatment with CORTICOSTEROIDS OR IVIG along with ASPIRIN, ANTICOAGULATION and supportive care.
• The morbidity and mortality can be quite high if left undiagnosed and untreated. A very high index of suspicion may be needed as was in this case.

CME INDIA Learning Points

• During the course of the coronavirus disease 2019 (COVID-19) pandemic, reports of a new multisystem inflammatory syndrome in children (MIS-C) have been increasing reported.
• Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe complication of SARS-CoV-2 infection in children and adolescents. Since June 2020, several case reports and series have been published reporting a similar multisystem inflammatory syndrome in adults (MIS-A). (CDC)
• Adult patients of all ages with current or previous SARS-CoV-2 infection can develop a hyperinflammatory syndrome resembling MIS-C.
• The pathophysiology of MIS in both children and adults is currently unknown.
• Antibody testing is usually required to identify SARS-CoV-2 infection in most of such cases. Clinical suspicion and indicated SARS-CoV-2 testing, including antibody testing, might be needed to recognize and treat adults with MIS-A.
• Clinical features in children have varied but predominantly include shock, cardiac dysfunction, abdominal pain, and elevated inflammatory markers, including C-reactive protein (CRP), ferritin, D-dimer, and interleukin-6
• We need today high alert for the recognition of an illness referred as multisystem inflammatory syndrome in adults (MIS-A) and the heterogeneity of clinical signs and symptoms, and the role for antibody testing in identifying similar cases among adults.
• Clinicians should consider MIS-A in adults with compatible signs and symptoms. These patients might not have positive SARS-CoV-2 PCR or antigen test results, and antibody testing might be needed to confirm previous SARS-CoV-2 infection.
• Because of the temporal association between MIS-A and SARS-CoV-2 infections, interventions that prevent COVID-19 might prevent MIS-A.
• Suggested MIS-A case definition includes the following five criteria:
  • A severe illness requiring hospitalization in a person aged ≥21 years;
  • A positive test result for current or previous SARS-CoV-2 infection (nucleic acid, antigen, or antibody) during admission or in the previous 12 weeks;
  • Severe dysfunction of one or more extrapulmonary organ systems (e.g., hypotension or shock, cardiac dysfunction, arterial or venous thrombosis or thromboembolism, or acute liver injury);
  • Laboratory evidence of severe inflammation (e.g., elevated CRP, ferritin, D-dimer, or interleukin-6); and
  • Absence of severe respiratory illness (to exclude patients in which inflammation and organ dysfunction might be attributable simply to tissue hypoxia).

CME INDIA Clinical Pearls

• Given the high proportion of MIS-C patients with negative PCR testing, clinical guidelines recommend the use of both antibody and viral testing to assist with diagnosis.
•  In patients with atypical or late manifestations of SARS-CoV-2 infection, including MIS-A, positive antibody results might be crucial to augment clinical recognition of this condition and guide treatment.
• The use of a panel of laboratory tests for inflammation, hypercoagulability, and organ damage (e.g., CRP, ferritin, D-dimer, cardiac enzymes, liver enzymes, and creatinine) might assist in the early identification and management of this COVID-19–associated (MIS-A ) condition.

CME INDIA Tail Piece

Reference:

1. Godfred-Cato S, Bryant B, Leung J, et al.; California MIS-C Response Team. COVID-19–associated multisystem inflammatory syndrome in children—United States, March–July 2020. MMWR Morb Mortal Wkly Rep 2020;69:1074–80. 
2. CDC. Information for healthcare providers about multisystem inflammatory syndrome in children (MIS-C). Atlanta, GA: US Department of Health and Human Services, CDC; 2020. https://www.cdc.gov/mis-c/hcp/
3. Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19. Nat Med 2020;26:1017–32. CrossRefexternal icon PubMedexternal icon
4. Henderson LA, Canna SW, Friedman KG, et al. American College of Rheumatology clinical guidance for pediatric patients with multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 and hyperinflammation in COVID-19. version 1. Arthritis Rheumatol 2020
5. Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection — United Kingdom and United States, March–August 2020 Weekly / October 9, 2020 / 69(40);1450–1456MMWR.
6. Elias MD, McCrindle BW, Larios G, et al. Management of Multisystem Inflammatory Syndrome in Children Associated With COVID-19: A Survey From the International Kawasaki Disease Registry. CJC Open. 2020 Nov;2(6):632-640. DOI: 10.1016/j.cjco.2020.09.004.

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