Clinical Characteristics of Sarcoidosis in an Asian Population

By Patompong Ungprasert, MD

Sarcoidosis is a chronic granulomatous disease of unknown etiology believed to be a result of a complex interaction between host factors and environmental triggers. We know that ethnicity influences the epidemiology and clinical phenotype of sarcoidosis. For instance, the annual incidence of sarcoidosis is as high as 70 per 100,000 population among Blacks Americans, but is as low as 1-2 per 100,000 population among Asians and Hispanics. In addition, Blacks with sarcoidosis tend to have more advanced stages of pulmonary sarcoidosis, higher frequency of extrathoracic involvement and a higher mortality rate than whites.1 However, data on clinical manifestations of sarcoidosis in Asians are still relatively limited.

A 14-year single center retrospective cohort study from Thailand

Together with collaborators from Mahidol University, the largest teaching hospital in Bangkok, Thailand, I conducted a study using the medical record-linkage system and the pathology database of Siriraj Hospital. Results from our study were presented in a poster at ACR Convergence 2020.2

In our study, we identified and retrieved data on patients with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for sarcoidosis (D86 – D86.9) treated between 2005 and 2018 using the medical record-linkage system. We also identified and retrieved data regarding patients with histopathology positive for non-necrotizing granuloma or non-caseating granuloma from the pathology database from the same time period. We then conducted medical record review of all potential cases from either source to confirm the diagnosis of sarcoidosis, which required compatible clinical pictures supported by presence of non-caseating granuloma, radiographic evidence of intrathoracic sarcoidosis and exclusion of other granulomatous diseases, especially tuberculosis. We deemed the presence of caseous granuloma as an acceptable alternative if extensive investigations for other causes of granulomatous inflammation, especially tuberculosis, were negative.

We identified a total of 89 confirmed cases of sarcoidosis. Of patients in the cohort, 80.9% were female; the mean age at diagnosis was 46.8 years (standard deviation [SD] 13.9 years) and the mean follow-up time of 5.4 years (SD 4.5 years). The majority of patients in this cohort had intrathoracic disease (81 cases; 91.0%). About half had stage I pulmonary sarcoidosis (43 cases; 53.1%), followed by stage II (32 cases; 39.5%), stage III (five cases; 6.2%) and stage IV (one case; 1.2%). However, fewer than half of patients with intrathoracic disease were symptomatic (34 cases; 41.9%) with dyspnea and cough being the most common symptoms (25.9% and 22.2%, respectively). The yield of intrathoracic biopsy was fair, as histopathology was positive for non-caseating granuloma in 52 of 68 patients (76.5%) who underwent biopsy.

Extrathoracic disease was common in this cohort, accompanying pulmonary sarcoidosis in 53 patients (65.4%). Eight patients had isolated extrathoracic disease. The most common extrathoracic disease was sarcoid uveitis (35 cases; 39.3%; four males and 31 females), followed by cutaneous sarcoidosis (24 cases; 26.9%), extrathoracic lymphadenopathy (18 cases; 22.5%) and sarcoid arthropathy (four cases; 4.5%).

A total of 48 patients (53.9%) received at least one systemic treatment during the course of their illness. Oral prednisolone was the most commonly prescribed systemic treatment (46 cases; 51.7%), followed by methotrexate (16 cases; 17.9%), azathioprine (eight cases; 9.0%) and chloroquine (three cases; 3.4%). Topical and inhaled corticosteroids were also frequently used (31.5% and 6.7%, respectively).

Distinguishing features of sarcoidosis in Thailand

The high prevalence of uveitis and marked female predominance are the most prominent findings in this study. Prevalence of uveitis was almost 40%, which is far higher than previous reports of 10%-15% in Europe and North America. However, a similarly high prevalence of uveitis was previously reported by a study from Japan.3 Thus, the current study may provide another piece of evidence to support that uveitis is much more common among Asian patients with sarcoidosis.

This cohort had a female-to-male ratio of about 4:1, which is much higher than the slight female predominance in cohorts of white and Black patients, for which the ratio is less than 2:1.

Hypercalcemia was seen in 16% of patients who had at least one calcium level available in their medical records, which is comparable to reports from North America. Since hypercalcemia in chronic granulomatous disease is driven by vitamin D, one could hypothesize that a geographic area with a higher intensity of sunlight and ultraviolet rays could have a higher prevalence of sarcoidosis-related hypercalcemia; however, the result of this study does not support this theory.

Potential biases

Since our study included a database from only one tertiary care center, the cohort may not be representative of all patients with sarcoidosis in the country (i.e., referral bias). Relying on ICD-10-CM codes also limited the accuracy of diagnosis and completeness of case identification. In addition, there was no specific protocol for documentation and some important data may not be documented in medical records as a result.

References

1. Judson MA, Boan AF, Lackland DT. The clinical course of sarcoidosis: presentation, diagnosis, and treatment in a large white and black cohort in the United States. Sarcoidosis Vasc Diffuse Lung Dis. 2012 Oct;29(2):119-127.
2. Tripipitsiriwat A, Komoltri C, Ruangchira-Urai R, Ungprasert P. Clinical characteristics of sarcoidosis in Asian population: a 14-year single center retrospective cohort study from Thailand. [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10).
3. Morimoto T, Azuma A, Abe S, et al. Epidemiology of sarcoidosis in Japan. Eur Respir J. 2008;31(2):372-379.