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).