Brigham and Women's Hospitals

Rheumatology

Updated: June 19, 2020

Managing COVID in Rheumatic Disease

  1. Please enroll patients with rheumatologic/autoimmune disease who are diagnosed with COVID-19 into the COVID-19 Global Rheumatology Alliance Registry and/or the EULAR – COVID-19 Database.
  2. Clinical Presentation:
  1. Patients with rheumatologic disease are not known to differ from other patients in terms of clinical presentation of COVID-19, though further information will be elucidated from the studies of the Global Rheumatology Alliance Registry.
  1. A report of 86 patients with immune-mediated inflammatory disease in New York reported high percentages of patients with fever (84%), cough (42%) and shortness of breath (41%), with lower rates of diarrhea, rhinorrhea and loss of taste and smell. Similar to reports from immunocompetent patients. (Haberman et al, NEJM, 2020) Similar findings were found in smaller studies of patients with rheumatic disease: 13 patients with chronic arthritis in Italy (Monti S et al. Ann Rheum Dis, 2020) and 52 rheumatic disease patients in Boston (D’Silva K et al. Ann Rheum Dis, 2020)
  1. Outcomes:
  1. Studies looking at outcomes for COVID patients with rheumatic disease are limited to date, and major conclusions cannot be drawn at this time.
  1. Incidence appears to be similar to the general population
  1. In one prospective case series of 86 patients in New York City with a variety of immune-mediated inflammatory diseases. (Haberman et al, NEJM, 2020)
  1. Hospitalization and mortality rates appear similar to the general population
  1. In one comparative cohort study of 52 patients with rheumatic disease (75% on immunosuppressive medications) hospitalization and mortality rates were similar. However, rheumatic patients were more likely to require mechanical ventilation than healthy comparators, though the number of patients was low (11 patients [48%] vs 7 patients [18%], multivariable OR with 95% CI 1.07 to 9.05).(D’Silva K et al. Ann Rheum Dis, 2020)
  2. In a case series from the Global Rheumatology Research Alliance of 600 patients with rheumatic disease and COVID-19 from 40 countries, glucocorticoid exposure >= 10mg daily was associated with modestly higher odds of hospitalization (OR 2.05, 95% CI 1.06-3.96) while use of anti-TNF agents was associated with lower odds of hospitalization (OR 0.40, 95% CI 0.19-0.81). Neither use of DMARDs nor NSAIDs changed odds of hospitalization. (Gianfrancesco M et al. Ann Rheum Dis 2020)
  1. Management:
  1. Data are evolving. We have included our recommendations below based upon guidelines as developed by the American College of Rheumatology. The authors also have outlined a helpful resource on UptoDate.
  2. General Management
  1. Patients should be counseled on general measures to prevent infection including physical distancing, hygiene, and wearing masks.
  2. For physician follow-up, telemedicine or video visits should be used when possible.
  3. Decrease frequency of routine laboratory testing or other in-person health care exposures where possible and safe.
  1. Pharmacologic treatment for patients without infection with or exposure to COVID-19
  1. Most anti-inflammatory and immunosuppressive medications including DMARDs and biologics may be continued or started.
  1. This recommendation applies to hydroxychloroquine, chloroquine, sulfasalazine, methotrexate, leflunomide, tacrolimus, cyclosporine, mycophenolate mofetil, azathioprine, tocilizumab, anakinra, and NSAIDs.
  2. In patients with systemic inflammatory or organ-threatening disease, glucocorticoids and immunosuppressants in high doses can be started.
  3. Jak inhibitors block signaling through multiple cytokine receptors, including interferons, which are important for the body's antiviral immune response. In theory, these effects may considerably increase the risk of complications from COVID-19. Until more data are available, clinicians may want to choose other classes of medications for patients in need of a new immunosuppressive treatment. For patients already taking Jak inhibitors with good disease control, these medications can be continued.
  1. Doses of most anti-inflammatory and immunosuppressive medications should not generally be reduced
  1. This is especially in instances where the patient has a history of organ-threatening rheumatic disease
  2. Glucocorticoids should be reduced to the lowest safe dose as deemed by the treating physician, though should not be abruptly stopped.
  1. Pharmacologic treatment for stable patients after exposure to COVID-19 (without symptoms)
  1. Continue medications such as: hydroxychloroquine, sulfasalazine, and NSAIDs.
  2. If safe to do so, stop other immunosuppressive medications temporarily with the possibility to restart after a negative test result for COVID-19 or after 2 weeks of observation without symptoms.
  1. The panel noted that it is not clear whether to stop methotrexate or leflunomide.
  2. In certain cases, IL-6 inhibitors may be continued pending shared decision-making with the patient’s provider.
  1. Pharmacologic treatment in rheumatic patients with confirmed or suspected COVID-19 infection
  1. Continue medications such as: Hydroxychloroquine and chloroquine
  2. If safe to do so, stop: sulfasalazine, methotrexate, leflunomide, azathioprine, mycophenolate mofetil, non-IL-6 biologics, and JAK inhibitors.
  1. It was agreed that NSAIDs should be stopped in patients with severe respiratory symptoms, unclear if NSAIDs should be stopped in patients without severe symptoms.
  2. In certain cases, it’s possible IL-6 inhibitors can be continued as part of a shared-decision making process.

Rheumatic Manifestations of COVID-19

  1. COVID-19 can cause a number of symptoms that may overlap with those seen in rheumatologic diseases as outlined below. For patients with established rheumatologic disease who have confirmed or suspected COVID-19, careful evaluation will be required to determine if their symptoms are due to flare of the disease or are sequelae of viral infection. Other patients who have persistent or unexplained rheumatic symptoms may benefit from a rheumatology consult to determine if there are additional concerns for underlying rheumatologic disease.
  1. Arthralgias, Myalgias, Myositis
  1. Myalgia or arthralgia occur in approximately 15% of patients.
  1. 14.8% of patients (based on analysis as of 2/20/2020 on 55924 cases. (WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) 2020)
  2. Myalgia or arthralgia in 14.9% of 1099 patients in mainland China (Guan et Al, NEJM, 2020)
  1. Occasionally arthralgia can be a presenting feature.
  1. Observation of one female patient in Thailand who presented with fever and low platelet count, initially misdiagnosed as Dengue. (Joob et al, Rheum Int, 2020)
  1. Rhabdomyolysis is also a potential late complication of Covid-19. (Tong et al, Emerg Infect Dis. 2020, Ronco et al, Nat Rev Nephrol, 2020)
  1. Please see Muscle Injury under Neuromuscular Disorders
  1. Parenchymal Lung Disease
  1. Please see Radiology and Acute Lung Injury
  1. Pericarditis and Myocarditis
  1. Please see Pericarditis and Myocarditis
  1. Cytokine Storm / Secondary HLH
  1. Please see Cytokine Storm
  1. Kawasaki-like Multisystem Inflammatory Syndrome in Children
  1. Please see section below
  1. Livedo Reticularis
  1. Please see Vasculopathies and Livido
  1. Pernio- or Chilblain-like lesions of hands and feets (“COVID toes”)
  1. Please see Perniosis
  1. Fever
  1. Please see Clinical Course
  1. Coagulopathy
  1. Please see Thrombotic Disease
  1. Elevated levels of inflammatory markers
  1. including CRP, ESR, and ferritin as well as elevated levels of cytokines including IL-1 and IL-6. Please see Diagnostics
  1. Lymphocytopenia and thrombocytopenia
  1. Can be present in active lupus, is also be seen in COVID-19 infection. Please see Lymphocytopenia and Thrombocytopenia

Multisystem Inflammatory Syndrome in Children (MIS-C)

  1. Multisystem Inflammatory Syndrome in Children (MIS-C), also known as Pediatric Inflammatory Multi-System Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS or PIMS), is a relatively rare manifestation of COVID-19 that has been described now in children and some young adults in multiple case series. (Panupattanapong et al, Cleve Clin J Med, 2020, Riphagen et al, Lancet, 2020, Verdoni et al, Lancet, 2020, Toubiana et al, BMJ, 2020, Pouletty et al, Ann Rheum Dis. 2020, Jones et al, Hosp Pediatr, 2020)
  1. It appears to be a late (i.e. post-viral) manifestation that occurs as a reaction to COVID-19 rather than directly by the virus, as many of the patients presented 2-3 weeks after the peak of infection in the area and had negative COVID-19 PCR testing but positive serologies. (Panupattanapong et al, Cleve Clin J Med, 2020)
  2. MIS-C has manifestations that overlap with Kawasaki disease and toxic shock syndrome.
  3. MIS-C compared to Kawasaki disease
  1. Typical Kawasaki disease is a generally self-limited febrile illness affecting young children characterized by symptoms that, in addition to fever, can include a diffuse polymorphic rash, erythema and edema of the palms and soles, conjunctivitis, oral mucosal changes (classic “strawberry tongue”), and cervical lymphadenopathy. It can cause coronary artery aneurysm if left untreated.(Panupattanapong et al, Cleve Clin J Med, 2020)
  2. Kawasaki disease was suspected to be a post-viral phenomenon even before COVID-19
  1. MIS-C occurs in an older patient population than Kawasaki disease. Kawasaki disease tends to occur in very young children, mean age of 2 years, but essentially always < 5 years old, whereas the average age of MIS-C patients is 8 years old.Symptoms include:
  1. Fever, rash, conjunctivitis, distal extremity edema, and GI symptoms including abdominal pain, nausea, vomiting, and non-blood diarrhea. In some cases, the GI symptoms occurred 1-2 weeks prior to their presentation for clinical care and may represent the period of acute infection with COVID-19.
  2. Severe cases can cause cardiac dysfunction and shock. Unlike the case in adults, respiratory symptoms are rare.
  1. Laboratory abnormalities include:
  1. Lymphopenia, neutrophilia, thrombocytopenia, and marked elevation of inflammatory markers including CRP and ferritin. D-dimer and elevated triglycerides are also common. Many patients also have evidence of cardiac involvement with elevated NT-proBNP and/or troponin-T.
  1. Management
  1. Draft guidelines have been released by the American College of Rheumatology (https://www.rheumatology.org/Portals/0/Files/ACR-COVID-19-Clinical-Guidance-Summary-MIS-C-Hyperinflammation.pdf) (Kawasaki disease and many etiologies of pediatric macrophage activation syndrome are managed by rheumatology.)
  1. Current treatment recommendations include low-dose aspirin as well as corticosteroids IVIG. High-dose anakinra (IL-1 blockade) can also be considered depending on the severity. Anticoagulation is recommended for patients with very large coronary aneurysms, documented thrombosis, or reduced ejection fraction.
  2. Multidisciplinary management of the pediatrics/ICU team with infectious disease, cardiology, rheumatology, and hematology services is recommended.
  3. Formal treatment guidelines are expected later in summer 2020.

Patients on Immunosuppressants

Rheumatology

  1. See Rheumatology

Neurology

  1. Please see Neuromuscular disorders
  2. Please see Multiple Sclerosis and Neuromyelitis Optica

Gastroenterology

  1. See Inflammatory Bowel Disease

Dermatology

  1. See Outpatient Dermatology

HIV

  1. Please see HIV section of the Infectious Disease chapter

Transplant

  1. This section is under development
  2. See also Cardiac Transplant section