AOSD lacks a specific diagnostic test and relies on excluding other conditions due to its non-specific symptoms. This often leads to a considerable delay in achieving a definitive diagnosis, as its presentation can overlap with various other medical conditions. [2, 16].
In this study, the incidence rate of AOSD was 0.625 cases per year which is lower than those calculated by other epidemiological studies [1]. The observed variation in results may be due to false diagnosis and subsequent treatment of patients for alternative medical conditions. Although this is a tertiary care center that caters to patients from all across the country, it is worth mentioning that the majority of patients originate from nearby areas.
Our study encompassed individuals aged 26 to 77, aligning with prior findings that AOSD predominantly affects younger adults, rarely impacting those over 60 [17]. The mean age in our study was 37.6 years, similar to an Italian study (mean 38.8) [14]. In contrast, Canadian and Indian literature reported mid-to-late 20s mean ages [13, 15], while others cited early 30s [10, 12]. AOSD exhibits a bimodal age distribution, with peaks at 15-25 and 36-46 [18, 19]. ]. Notably, our mean age may be skewed due to a study outlier (1 patient aged 77).
Although AOSD is widely thought to have female predominance [6], existing literature also portrays a higher incidence in men [10, 15]. Multiple studies have also shown equal sex distribution [11, 13, 14, 18]. Our cases exhibited a higher incidence in females. While females are commonly associated with a higher autoimmune disease risk, males with similar symptoms should also be considered for this condition.
Among our patients the most frequent findings included fever, arthralgia, neutrophilic leukocytosis and abnormal LFTs, these findings align with conclusions reached by previous studies [10–15]. Furthermore, our findings of elevated ESR and hyperferritinemia were comparable to other studies [10–15]. Hepatosplenomegaly was observed in 50% of the patients who presented with AOSD; this was similar to its prevalence in previous studies that showed low-moderate occurrence of hepatosplenomegaly which was assessed through physical examination, ultrasound or other imaging modalities [11–14]. Overall, the results of clinical, laboratory, and radiological findings in our study were parallel to the ones reported in other epidemiological studies.
In our patient population, the characteristic salmon-coloured maculopapular rash was seen in 62.5%, while comparable results (57%) were portrayed by a study in India [15]. However, studies from other regions including China, Italy, and Greece, showed a higher proportion [11–14]. This discrepancy in data between Southeast-Asia and other regions may be explained by the fact that people in Southeast-Asia have a darker skin tone making it difficult to spot mild rashes.
At the time of presentation, sore throat and lymphadenopathy was noted in 37.5% of our cases and this was comparable to another study with similar findings [15]. In contrast, multiple studies reported sore throat in over 50% of the cases [14–17, 19], and a few had nearly 80% or more [11–13]. Similarly, higher frequencies (>50%) of lymphadenopathy were observed in the majority in other studies [10, 12–15]. 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 being unable to recall this symptom along with the other manifestations. With regards to lymphadenopathy, variation may be explained by the dynamic lymph node changes during the disease process. With more progress in this field we may be able to understand the disease progression better and unravel the exact triggers and cellular responses that lead to AOSD.
Pharmacological management of AOSD is centered around glucocorticoids, NSAIDs, and disease-modifying anti-rheumatic drugs (DMARDs)(eg methotrexate, hydroxychloroquine, etc) [20]. High-dose corticosteroids are preferred for inducing remission when systemic symptoms predominate [20]. Prednisolone served as the initial treatment in our cases.
If corticosteroids fail to elicit a response, second-line options include DMARDs and biologics [21]. Biological agents can be useful in AOSD refractory to DMARD and Steroid treatment [22]. Biologics, like IL-1 receptor antagonist Anakinra, can reduce corticosteroid doses and manage side effects, e.g., diabetes decompensation [23]. Other IL-1 inhibitors (rilonacept and canakinumab), TNF alpha inhibitors and anti-IFNγ antibody(emapalumab) are alternatives [2, 24, 25]. However, due to the higher costs of these agents, they are not commonly used [23], and it was not used in our patients either. Gradual steroid reduction and switching to these options enhance treatment compliance while minimizing corticosteroid-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 [6, 18 HYPERLINK "https://www.zotero.org/google-docs/?IbWvcU"]. 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 [26]. 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 provides valuable insights, but it's important to consider its limitations. It was conducted solely at a single-center tertiary care hospital, which, while drawing patients from diverse geographic regions, may not fully represent the broader national demographic and health diversity. This localized focus might limit the applicability of the epidemiological data collected here to the entire country.
Additionally, the study's relatively small sample size is a significant constraint. With a limited number of participants, generalizing findings becomes challenging. Small sample sizes can introduce sampling bias and limit statistical power, potentially hindering the detection of significant differences or associations. Therefore, it's advisable to exercise caution when extrapolating the study's outcomes and conclusions to larger, more diverse populations. Further research with more extensive and representative samples is warranted to ensure a more comprehensive understanding of the topic.