DISCUSSION
Chikungunya is an arboviral disease caused by an RNA virus with wide geographical distribution in endemic areas, and other tropical areas with seasonal characteristics that are favorable to development of disease vectors (Aedes aegypti and Aedes albopictus) (4). The chance of large outbreaks of CHIKV worldwide is high, especially in developing countries due to abundance of vectors (5). In 2007, an infected tourist from India introduced chikungunya to northern Italy, resulting in the identification of 292 suspected cases (6).
Chikungunya is self-limited and has a broad clinical spectrum, being characterized by a characteristic triad consisting of fever, arthralgia, and rash (5). The clinical course of the disease can be divided into acute and chronic phases. In acute phase, there may be fever, symmetrical polyarthralgia, headache, nausea, vomiting, fatigue, and myalgia. Arthralgia affects large and small joints and preferentially involves more distal regions such as ankles, wrists, and phalanges (4). Joint pain may persist, characterizing onset of chronic phase, which lasts for 12 weeks to years (4). The prevalence of chronic phase is highly variable and may affect more than half of the patients (1). Complications of cardiovascular, renal, respiratory, hepatic, gastrointestinal and adrenal systems are associated with the infection and are referred to as atypical features (3).
In addition, CHIKV, like other viruses, can act as a trigger for autoimmune diseases, among them, autoimmune inflammatory myopathies, a group of diseases characterized by presence of inflammation of skeletal muscle and subdivided into Dermatomyositis (DM), Polymyositis (PM), Necrotizing Autoimmune Myopathy (MAN), Inclusion Corpuscle Myopathy (ICM) and Anti-synthetase Syndrome (SAS), according to clinical, histological, immunopathological and autoantibody characteristics (7).
Autoimmune diseases are the result of hyperstimulation of immunity, caused by breakdown of immune tolerance, which has a multifactorial etiology. Among all potential triggers for development of autoimmune diseases, viruses represent the greatest environmental potential to trigger inflammatory myopathy (IM) in genetically susceptible individuals. Inflammatory myopathy has been observed during or after viral infection, but attempts to amplify viruses from muscles, including coxsackievirus, influenza, paramyxovirus, mumps, cytomegalovirus, and Epstein-Barr virus have failed. The best studied viral relationship so far has been with retrovirus (7). However, there are fewer case reports in the literature highlighting association of CHIKV with the development of autoimmune diseases, especially inflammatory myopathies (5,8).
Dev, et al (2019), reported a case of inflammatory myositis following Chikungunya infection in 2019 in India (8). Martins, et al (2016), reported a case of a patient presenting with myositis and encephalitis post-CHIKV infection in Brazil (5). However, this is the first case of antisynthetase syndrome post-chikungunya infection characterized in literature.
There are possible hypothesized mechanisms for development of post-infection-induced autoimmune disease. Autoreactive T cells can be activated by cross-linking with a viral antigen that bears similarity to autoantigen, and become pathogenic. Stimulation of Toll-like receptors and other pattern-recognition receptors on antigen-presenting cells leads to production of pro-inflammatory mediators, which can trigger tissue damage. Tissue destruction by T-cells and inflammatory mediators further increase release of autoantigens, potentiating the immune response (2).
Another possible mechanism is the evasion of host’s innate and adaptive immune responses by the virus, as seen in mice showing a chronic inflammatory process in ankles after inoculation with CHIKV RNA and persistence of the virus in the local tissue. Furthermore, several alphaviruses, including CHIKV, have been shown to antagonize STAT activation by type I and type II interferon (9).
ASS is a rare disease with unknown incidence and a prevalence twice higher in females. It presents a broad clinical picture, with proximal muscle weakness, arthritis, arthralgia, Raynaud’s phenomenon, fever, ”mechanic’s hands” and interstitial lung disease. It is related to presence of anti-synthetase autoantibodies, especially anti-Jo-1, and to histological presentation of perimysial and perifascicular muscle fiber necrosis. Pulmonary involvement is related to high morbidity and mortality rates, especially interstitial lung disease (ILD), which can present with dyspnea, cough, and chest pain (7).
In this case, the patient presented with proximal muscle weakness in all four limbs, MRI of thighs showing a muscular inflammatory process, electroneuromyography with a myopathic pattern, interstitial pneumopathy, and a reagent Anti-Jo1 antibody, in addition to joint involvement. The case report presented some limitations, such as the fact that the patient did not perform a muscle biopsy, due to lack of availability of the procedure at the service. The patient also did not present mechanic’s hands, a classic but not specific sign (10).