The diagnosis of AOSD is currently reliant on a cluster of nonspecific clinical symptoms, thus the lack of specific tests for AOSD makes it an enigmatic diagnosis of exclusion, with numerous differentials, leading to a big discrepancy between the initial presentation and establishment of a definitive diagnosis. (12)
Within this study, the calculated incidence rate of AOSD was 0.625 cases per year. However, this is moderately lower than those calculated by other epidemiological studies. (1) The disparity in the results may be due to the exclusion of those patients who were diagnosed prior to presenting at the hospital. It is noteworthy to mention that even though this tertiary care centre receives cases from all over the country, many cases are referred from places close to the localities of the people where they presented first.
Our cases presented in the range of ages 26–77 years, with one patient diagnosed at age 70. This is consistent with previous studies where AOSD has been cited as a disease mainly affecting younger adults, with a rare occurrence in individuals over the age 60 years.(13) Moreover, the mean age of the patients in this study was 37.7 years, which was similar to that of a study conducted in Italy in which the mean reported was 38.8.(10) However, literature from Canada and India presented a mean age of mid-to-late 20s,(9, 11) while other studies recorded a mean in the early 30s.(6, 8) Furthermore, AOSD has been observed to show a bimodal age distribution of 15–25 and 36–46 years of age.(14) It is possible that the mean of the data in this study became skewed because of an outlier - one patient was diagnosed at 77 years, shifting the mean to the right.
Although AOSD is more prevalent in females, (8) existing literature also portrays male preponderance. (6, 11) Our cases exhibited an equal distribution amongst males and females and this was also supported by prior studies showing no sex predisposition.(7, 9, 10) Where we suspect autoimmune diseases more in females due to their predisposition, we should also have a high degree of suspicion in males with a compatible presentation.
Fever, arthralgia, neutrophilic leukocytosis and abnormal LFTs were the most common findings amongst our patients and similar conclusions were drawn by other studies.(6–11) Furthermore, elevated ESR and hyperferritinemia were comparable to all other studies.(6–11) Hepatosplenomegaly was observed in 40% of the patients who presented with AOSD and this was paralleled by other studies also having a low to moderate occurrence of hepatosplenomegaly via physical examination, ultrasound or other imaging techniques.(7–10) We therefore see that the clinical, laboratory and radiological findings observed in our study are similar to the ones in other epidemiological studies.
The characteristic salmon-coloured rash was seen in 60% of our patients and similar results (57%) were portrayed by a study on AOSD from India. (11) However, studies from other regions like China, Italy, and Greece, showed a higher proportion. (7–10) The discrepancy in data between Southeast-Asian regions and others can be accounted for by the darker skin colour making it difficult to identify a mild rash.
Sore throat and lymphadenopathy at the time of presentation were noted in 30% of our cases and this was paralleled by another study with similar findings.(11) In contrast, multiple studies observed sore throats in over 50% of the cases,(10–14) and a few had near 80% or above.(7–9). Similarly, higher frequencies (> 50%) of lymphadenopathy were observed in the majority in other studies.(6, 8–11) The low proportion of sore throat in our study may be explained by its early onset in the disease process and possible delay in diagnosis of AOSD, resulting in patients not recalling it along with the other manifestations. With regards to lymphadenopathy, variation may be explained by the dynamic lymph node changes during the disease process.
Pharmacological management of AOSD is centered around glucocorticoids, NSAIDs, and disease-modifying anti-rheumatic drugs (DMARDs).(15) The use of corticosteroids is considered the first-line therapy when systemic symptoms predominate – a recent study concluded that the use of high dose corticosteroids was more effective in inducing remission than the use of low dose corticosteroids. Prednisolone was used as a first-line agent for our patients.
Disease modifying anti-rheumatic drugs (DMARDs) and biologic agents constitute second-line therapies in case corticosteroids fail to initiate a clinical response. (16) According to a case report, once a day administration of IL-1 receptor antagonist Anakinra led to the reduction of the dose of corticosteroids – which was useful in controlling the side effects of corticosteroids such as the decompensation of Diabetes Mellitus. However, due to the hefty cost, it is not commonly used, (17) and it was not used in our patients either. Therefore, wherever possible, tapering off steroids and switching to such alternatives can ensure better treatment compliance and prevent glucocorticoid related side effects.
MAS has been reported as the most severe complication of AOSD, seen in 10% with a mortality of 15.7% in one study, and an incidence of 15% with a high mortality rate between 10–41% in another.(3, 18) None of our patients were diagnosed with MAS likely due to the limited number of cases and the rarity of this complication. Interestingly, a lesser common complication associated with AOSD is pulmonary hypertension, (18) which was noted in 1 patient that presented with severe pulmonary arterial hypertension and associated cor pulmonale.
The only mortality reported in this study was of a 77-year old man. However, sufficient evidence is not present to support AOSD-related complications as the cause of death in this patient. One study reported the mean age of patients who died in hospitals as 62.4 years ± 3.1 and concluded that the older age and associated comorbidities were a predictive factor for the higher incidence of mortality in patients with AOSD.(19) Early identification of AOSD in an older patient therefore is more crucial.
This study highlights specific strengths as observed by the data and its interpretation. It assisted in the thorough analysis of AOSD symptoms and explored the Yamaguchi criteria extensively amongst all patients. Additionally, many of the frequencies observed in this study were comparable to those of other studies as well.
This study posed certain limitations. It was conducted in a single-center tertiary care hospital, and despite patients coming from all over the country, the patient sample’s epidemiological data is not reflective of the country’s population. Thus, limitations of this study should be considered alongside its findings.