ReviewPulmonary Disorders Induced by Monoclonal Antibodies in Patients with Rheumatologic Autoimmune Diseases
Section snippets
Pulmonary Disorders Induced by Monoclonal Antibodies
The prevalence, histopathology, and clinical manifestations of mAb-induced pulmonary disorders in rheumatologic autoimmune disorders have not been analyzed systematically. Most cases come from small case series or case reports; although some come from controlled and postmarketing studies.3 Table 1 shows a proposed classification of pulmonary involvement induced by mAb according to reported cases.
Interstitial Pneumonia
Data on therapeutic management were available in 50 cases and included withdrawal of biological agents in all cases but 1.31 Corticosteroids were used in 84% cases, with methylprednisolone pulses administered in one-third and immunosuppressive agents added in 8 cases. The mAb therapy was reinitiated in 1 case, with infliximab changed to etanercept to control the underlying disease, without further complications.32
Interstitial pneumonia outcomes were detailed in 48 cases, with complete
Pathophysiological Mechanisms
Of the 161 cases reviewed, 97% were associated with TNFα blockers. TNFα, a cytokine that is an essential component of the innate immunity, has a very complex network of interactions. TNFα is associated with two etiopathogenic processes closely related to idiopathic interstitial pneumonia and sarcoidosis: it is a pivotal cytokine in the pathophysiology of pulmonary fibrosis36, 37 and plays an essential role in the formation and maintenance of granulomas, as shown by studies of the
Patient Management
Although the evidence is based mainly on case reports and small series, and patients had other risk factors for interstitial lung disease such as rheumatoid arthritis and methotrexate, we suggest some recommendations for the management of patients with mAb-induced pulmonary diseases (Figure 1).
Conclusion
The mAbs have been used for rheumatologic autoimmune diseases but there are increasing reports of the paradoxical induction of autoimmune processes due to these agents, overwhelmingly anti-TNF. To date, over 150 cases of drug-induced pulmonary disease have been reported, mostly from uncontrolled studies, meaning solid conclusions are not possible. Concerns include the variable incidence of induced disease according to ethnic group, underlying disease and activity, type of study, possible
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2017, Journal of Allergy and Clinical ImmunologyCitation Excerpt :TNF inhibitor therapy has been associated with cutaneous vasculitis and lupus-like syndromes that resolve on discontinuation of the inhibitor therapy.50 Other autoimmune phenomena associated with TNF inhibitors include cutaneous psoriasis, sarcoidosis, antiphospholipid syndrome, uveitis, interstitial lung disease, dermatomyositis, polymyositis, demyelinating disease, peripheral neuropathies, and autoimmune hepatitis.51-57,101 These complications occurred with both anti-TNF mAbs and the TNF receptor fusion protein etanercept, indicating that these reactions represent a drug class effect of TNF blockers.
Consensus statements for medical practice: Biological agents and lung disease [Abridged English translation by the Japanese Respiratory Society]
2017, Respiratory InvestigationCitation Excerpt :A5. Common symptoms include dyspnea, cough, and fever [82,83]. Q6.
Infection is the major trigger of hemophagocytic syndrome in adult patients treated with biological therapies
2016, Seminars in Arthritis and RheumatismCitation Excerpt :In 2006, the Study Group on Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine created the BIOGEAS project (www.biogeas.org), a multicenter study dedicated to collecting data on the use of biological agents in adult patients with systemic autoimmune diseases [9]. An additional objective of the BIOGEAS project is to collect data on autoimmune diseases secondary to the use of biological agents and BIOGEAS has published several articles on this topic [5–8]. We search the MEDLINE database for articles published between January 1996 and August 2013 containing the terms “hemophagocytic syndrome,” “macrophage activation syndrome,” “hemophagocytic lymphohistiocytosis.”
Funding: None.
Conflict of Interest: None of the authors has any conflict of interest associated with the work presented in this manuscript.
Authorship: All authors had access to the data and played a role in writing this manuscript.