Antithyroid Arthritis Syndrome – A Rare Complication of Methimazole Therapy

DISCUSSION:

Hyperthyroidism is primarily managed with antithyroid drugs (ATD), including methimazole (MMI) and propylthiouracil (PTU). MMI has become the main therapeutic agent due to its superior safety profile compared to PTU. However, the side effects of MMI ranges from mild manifestation like skin reaction to severe complications like hemophagocytic syndrome [5] and anti-neutrophil cytoplasmic antibody [ANCA]-associated vasculitis [AAV]). While AAV may present with polyarthritis, these articular symptoms are not pathognomonic and require differentiation from a distinct complication – antithyroid arthritis syndrome (AAS).

AAS caused by thionamides and propylthiouracil was originally described in 1946 by Williams et al. [6] Antithyroid drug-induced arthritis can be part of the AAS or ANCA-Associated Vasculitis (AAV). Unfortunately, its course can be unpredictable and rarely even fatal, leading to renal and respiratory failure. Most cases present initially with arthralgia. Arthritis, when compared to arthralgias are associated with synovitis, raised markers of inflammation such as leukocytosis, elevated CRP and ESR. [2] Discontinuation of therapy is warranted early as it may lead to severe transient migratory polyarthritis. An adverse reaction to any drug is based on several factors. Temporal association, clinical features, organ involvement, significant improvement of symptoms following the withdrawal of the drug (dechallenge) and reappearance of the symptoms on repeated exposure to the drug (rechallenge).[7] In our case, patient had a score of 7 on Naranjo Adverse Drug Reaction (ADR) probability scale, used for assessing adverse drug reactions suggesting high probability of relationship between Methimazole exposure and development of AAS.[8] It is important to rule out autoimmune diseases which can mimic antithyroid arthritis syndrome. In this case, the possibility of reactive arthritis and other autoimmune diseases like lupus were considered. RA factor, ANA and Anti-DNA were negative.

AAS is a rare adverse reaction caused by ATDs, characterized by fever, rash, and myalgia, with arthralgia in the joints of the lower limbs, and even in the wrists and forearms. [9] Epidemiological data is limited; 1.6% incidence has been reported in patients exhibiting polyarthralgia. [3] AAS must be distinguished from ANCA-associated vasculitis (AAV), which shares articular manifestations but requires different approach to treatment. Unlike AAV, AAS typically lacks ANCA seropositivity and systemic organ involvement. Autoimmune tests such as ANA, ANCA, and drug lymphocyte stimulation tests (DLST) can help distinguish AAS from other rheumatic condition, but the results are not definitive. [9] As with most adverse drug reactions, discontinuation of suspected medications and symptomatic treatment with NSAIDs and corticosteroids can be an effective approach to AAS, but use of colchicine was also reported as a new approach. [2]

CONCLUSION:

Antithyroid arthritis syndrome is a rare complication of antithyroid medications. It comprises of a variety of symptoms such as myalgia, arthralgia and arthritis along with fever and rash of varying severity. It has non-specific laboratory findings, making the diagnosis clinically challenging. Following diagnosis, immediate discontinuation of the responsible drug is needed for resolution of symptoms as sometimes it can rapidly progress to a life-threatening condition. Continuation of treatment without proper recognition or rechallenge with even smaller doses can prove to be dangerous. In conclusion, our case report underlines the importance of differential diagnosis and recognition of AAS as an adverse effect of antithyroid agents and the need for prompt withdrawal of the offending drug.

CONFLICT OF INTEREST: Nil

ACKNOWLEDGEMENT:

The author is thankful to the GM (Medical services) for allowing her to send the manuscript for publication.

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