Key Points
Question
What are the incidence and prevalence of granuloma annulare in the United States, and do they vary by sociodemographic factors?
Findings
In this cross-sectional study of 11 608 patients with incident granuloma annulare and 17 862 patients with prevalent granuloma annulare, granuloma annulare had an annualized incidence of 0.04% and an annualized prevalence of 0.06%, with a 3:1 female to male ratio, and a peak incidence and prevalence in the fifth decade of life.
Meaning
The findings of this study suggest that granuloma annulare is a rare disease in the United States that predominantly affects women and middle-aged to older individuals.
Abstract
Importance
Although several single-center studies have estimated that granuloma annulare may account for approximately 0.1% to 0.4% of new patients presenting to dermatologists, large-scale population-based studies estimating the prevalence and incidence of granuloma annulare are lacking.
Objectives
To estimate the population-based incidence and prevalence of granuloma annulare in the United States and to identify the most commonly prescribed treatments.
Design, Setting, and Participants
This cross-sectional study used deidentified data from the Optum Clinformatics Data Mart Database from January 1, 2017, to December 31, 2018, to identify patients with granuloma annulare.
Main Outcomes and Measures
After validating an approach to classify patients with granuloma annulare using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes, the primary outcomes were age-, sex-, and race/ethnicity-specific annualized incidence and prevalence estimates for granuloma annulare. In addition, treatment use within 6 to 12 months after the first diagnosis of granuloma annulare was examined. Confidence intervals for prevalence and incidence estimates were computed assuming a binomial distribution using the Wilson score method. Age-, sex-, and race/ethnicity-specific incidence and prevalence estimates were compared using the χ2 test.
Results
A total of 11 608 patients with incident granuloma annulare (8680 female patients [74.8%]; mean [SD] age, 56.5 [18.8] years) and 17 862 patients with prevalent granuloma annulare (13 548 female patients [75.8%]; mean [SD] age, 56.6 [18.5] years) were identified during the study period. The overall annualized incidence of granuloma annulare was 0.04%, or 37.9 (95% CI, 36.9-38.9) per 100 000, and the overall annualized prevalence of granuloma annulare was 0.06%, or 58.3 (95% CI, 57.1-59.5) per 100 000. The incidence and prevalence of granuloma annulare were highest in the fifth decade of life. The incidence and prevalence of granuloma annulare were higher among women (incidence: female to male ratio, 2.8:1; prevalence: female to male ratio, 3.0:1). Within 6 months of their first diagnosis, 4822 patients (41.5%) filled a prescription for a topical corticosteroid, and 1087 patients (9.4%) received an intralesional injection. Within 6 months of their first diagnosis, oral tetracycline prescriptions were filled by 820 patients (7.1%), and hydroxychloroquine prescriptions were filled by 268 patients (2.3%).
Conclusions and Relevance
Granuloma annulare is a rare disease in the United States that is more common among women and middle-aged to older individuals. The findings of this cross-sectional study provide important background regarding the basic epidemiology and overall burden of granuloma annulare in the United States. Future studies are needed to better understand the association of granuloma annulare with quality of life and the most optimal treatment approaches for this condition.
This cross-sectional study estimates the population-based incidence and prevalence of granuloma annulare in the United States and identifies the most commonly prescribed treatments.
Introduction
Granuloma annulare is a granulomatous skin condition of uncertain pathogenesis.1 Clinically, it is characterized by ringed, erythematous plaques. Subcutaneous variants have also been described.2 The most common form of granuloma annulare is the localized variant, but it is thought that approximately 15% to 25% of patients who seek care will have generalized disease.3,4,5 Although granuloma annulare may occur as an isolated skin-limited disease, several potential associations have been described, including diabetes and hyperlipidemia,5,6,7,8,9,10,11,12 as well as autoimmune conditions, such as thyroid disease.13,14 Although there are no US Food and Drug Administration–approved treatments for granuloma annulare, commonly described treatment approaches include topical corticosteroids, topical calcineurin inhibitors, and intralesional corticosteroids. For more widespread disease, hydroxychloroquine, phototherapy, oral tetracycline-class antibiotics, dapsone, systemic retinoids, tumor necrosis factor (TNF) inhibitors, and other medications are considered.1,14,15
Although several single-center studies have estimated that granuloma annulare may account for approximately 0.1% to 0.4% of new patients presenting to dermatology clinics, there is a lack of large-scale population-based studies estimating the prevalence and incidence of granuloma annulare.3,14,15,16,17 In smaller, single-center studies, granuloma annulare is most commonly reported in patients in the first 3 to 5 decades of life, with a female to male ratio of approximately 2:1.3,17
Given the limited epidemiologic data available for granuloma annulare, the burden of disease has not been well established. The selected samples and small cohorts used in prior studies limit the generalizability of these studies to the broader population. In addition, the incidence and prevalence estimates from these studies are often based on patients presenting to a dermatology clinic, which may not reflect the true population-based incidence and prevalence.17 The purpose of this study was to estimate the population-based incidence and prevalence of granuloma annulare in the United States as well as to understand the most common treatments prescribed for these patients.
Methods
Data Set Source
This retrospective cross-sectional study used deidentified data from the Optum Clinformatics Data Mart Database from January 1, 2017, to December 31, 2018, to identify patients with granuloma annulare. The Optum Clinformatics Data Mart includes deidentified commercial claims data for approximately 18 million to 20 million covered individuals in the United States annually. These data include both medical and pharmacy claims as well as patient demographic information, such as age and sex. The demographic information of the patient population available in the Optum Clinformatics Data Mart is similar to that of the United States population with respect to sex, age, and geographical distribution.18 Optum derives socioeconomic data from health information deterministically linked to data licensed from a consumer data vendor. The member’s ethnicity is derived by using the member’s name and geographic location. Once member’s ethnicity is determined, it is mapped to 1 of 5 race categories (Asian, Black, Hispanic, White, or unknown or other). This study was approved by the institutional review board of the University of Pennsylvania and patient consent was deemed exempt because the data were deidentified. It was conducted in adherence with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline and the Reporting of Studies Conducted Using Observational Routinely Collected Health Data (RECORD) guideline.19
Optimal ICD-10 Code Classification Approach to Identify Patients With Granuloma Annulare
To validate the use of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes to identify patients with granuloma annulare (code L92.0), a medical record review was performed among a random sample of 100 patients who were evaluated in the outpatient dermatology and primary care clinics at the University of Pennsylvania Health System between January 1, 2016, and October 31, 2020, and who had at least 1 ICD-10 code for granuloma annulare. A control cohort was composed of a random sample of 100 patients from the same clinical settings who did not have a code for granuloma annulare.
A focused review was conducted on each medical record to determine whether there was documentation of clinical granuloma annulare in either the physical examination or treatment plan discussion. It was also recorded whether each patient had a subsequent visit with another ICD-10 code for granuloma annulare within 12 months or whether each patient was prescribed a potential treatment for granuloma annulare within 6 months of the first code. A focused medical record review in the control group was conducted to evaluate for any documentation consistent with granuloma annulare.
A single ICD-10 code for granuloma annulare had a positive predictive value of 0.94 (95% CI, 0.84-0.99) in the dermatology setting and 0.82 (95% CI, 0.69-0.91) in the primary care setting. The negative predictive value for the absence of an ICD-10 code for granuloma annulare was 1.00 (95% CI, 0.93-1.00) in both settings. Although 2 encounters with a code for granuloma annulare had a slightly higher positive predictive value (dermatology, 1.00; 95% CI, 0.88-1.00; primary care, 0.92; 95% CI, 0.62-1.00), 38.3% of patients with granuloma annulare (18 of 47) seen in the dermatology setting and 70.7% of patients with granuloma annulare (29 of 41) seen in the primary care setting were no longer identified using 2 codes compared with a single code. Similarly, although a single code and a relevant medication prescription within 6 months had a slightly higher positive predictive value (dermatology, 0.95; 95% CI, 0.84-0.99; primary care, 0.83; 95% CI, 0.61-0.95), 14.9% of patients with granuloma annulare (7 of 47) seen in the dermatology setting and 53.7% of patients with granuloma annulare (22 of 41) seen in the primary care setting were no longer identified using this approach compared with a single ICD-10 code. As a result, for the purposes of this study, a single ICD-10 code was used to identify patients with granuloma annulare.
Study Population and Outcomes
Because ICD-10 codes were implemented in October 2015 in the United States, to allow for uptake, the study period was between January 1, 2017, and December 31, 2018.20 The primary outcomes were age-, sex-, and race/ethnicity-specific annualized incidence and prevalence of granuloma annulare. Incident granuloma annulare was defined as the receipt of a new ICD-10 code for granuloma annulare for a patient with no prior ICD-10 codes for granuloma annulare and at least 180 days of continuous enrollment prior to this ICD-10 code for granuloma annulare. Prevalent granuloma annulare was defined as the receipt of any ICD-10 code for granuloma annulare during the calendar year. The entire population was considered at risk while continuously enrolled in the data set.
In addition, to evaluate medication and procedure use among patients with granuloma annulare, the frequency of use of topical corticosteroids, topical calcineurin inhibitors, hydroxychloroquine, oral tetracycline-class antibiotics (ie, doxycycline or minocycline), dapsone, systemic retinoids (ie, isotretinoin or acitretin), and TNF inhibitors in the 6 to 12 months after the first diagnosis of granuloma annulare was examined. Claims for medications were classified using National Drug Codes. Using Current Procedural Terminology codes, we examined the use of phototherapy (codes 96900, 96910, 96912, and 96913) and intralesional corticosteroids (codes 17110 and 17111) within 6 to 12 months after the first diagnosis of granuloma annulare. Subgroup analyses were performed among patients seen by a dermatologist vs those who were not seen by a dermatologist.
Statistical Analysis
The Wilson score method was used to compute 95% CIs for prevalence and incidence estimates, assuming a binomial distribution. The age-, sex-, and race/ethnicity-specific incidence and prevalence estimates were compared using the χ2 test. Statistical analyses were performed using Stata, version 16 (StataCorp) and Microsoft Excel (Microsoft Corp). All P values were from 2-sided tests and results were deemed statistically significant at P < .05.
Results
A total of 11 608 patients with incident granuloma annulare (8680 female patients [74.8%]; mean [SD] age, 56.5 [18.8] years) and 17 862 patients with prevalent granuloma annulare (13 548 female patients [75.8%]; mean [SD] age, 56.6 [18.5] years) were identified during the study period (Table 1). The overall annualized incidence of granuloma annulare was 0.04%, or 37.9 (95% CI, 36.9-38.9) per 100 000 (Table 2), and the overall annualized prevalence of granuloma annulare was 0.06%, or 58.3 (95% CI, 57.1-59.5) per 100 000 (Table 3).
Table 1. Demographic Characteristics of Patients With Incident or Prevalent Granuloma Annulare in the United States.
| Characteristic | Patients, No. (%) | |
|---|---|---|
| Incident (n = 11 608) | Prevalent (n = 17 862) | |
| Sex | ||
| Female | 8680 (74.8) | 13 548 (75.8) |
| Male | 2928 (25.2) | 4314 (24.2) |
| Age, y | ||
| ≤19 | 706 (6.1) | 936 (5.2) |
| 20-29 | 486 (4.2) | 670 (3.8) |
| 30-39 | 896 (7.7) | 1294 (7.2) |
| 40-49 | 1276 (11.0) | 1906 (10.7) |
| 50-59 | 2268 (19.5) | 3542 (19.8) |
| ≥60 | 5978 (51.5) | 9514 (53.3) |
| Race/ethnicity | ||
| White | 8454 (72.8) | 12 740 (71.3) |
| Black | 540 (4.7) | 776 (4.3) |
| Hispanic | 740 (6.4) | 1094 (6.1) |
| Asian | 192 (1.7) | 252 (1.4) |
| Other or unknown | 1684 (14.5) | 3000 (16.8) |
| Income, $ | ||
| <49 000 | 1830 (15.8) | 2682 (15.0) |
| 50 000-74 000 | 1554 (13.4) | 2330 (13.0) |
| 75 000-99 000 | 1520 (13.1) | 2338 (13.1) |
| ≥100 000 | 4020 (34.6) | 6068 (34.0) |
| Unknown | 2686 (23.1) | 4442 (24.9) |
| Educational level | ||
| Less than 12th grade | 22 (0.2) | 32 (0.2) |
| High school diploma | 2034 (17.5) | 2966 (16.6) |
| Less than bachelor degree | 5758 (49.6) | 8692 (48.7) |
| Bachelor degree plus | 2570 (22.1) | 3878 (21.7) |
| Unknown | 1224 (10.5) | 2296 (12.9) |
Table 2. Mean Annualized Incidence of Granuloma Annulare in the United States (January 1, 2017, to December 31, 2018).
| Population | Granuloma annulare cases, No. | Incidence per 100 000 (95% CI) | Incidence, % |
|---|---|---|---|
| All granuloma annulare cases | 5804 | 37.9 (36.9-38.9) | 0.04 |
| Sex | |||
| Female | 4340 | 55.2 (53.6-56.9) | 0.06 |
| Male | 1464 | 19.6 (18.6-20.6) | 0.02 |
| Age, y | |||
| ≤19 | 353 | 14.4 (12.9-16.0) | 0.01 |
| 20-29 | 243 | 14.4 (12.6-16.2) | 0.01 |
| 30-39 | 448 | 23.1 (21.0-25.3) | 0.02 |
| 40-49 | 638 | 34.6 (31.9-37.3) | 0.03 |
| 50-59 | 1134 | 58.6 (55.2-62.0) | 0.06 |
| ≥60 | 2989 | 54.5 (52.6-56.5) | 0.05 |
| Race/ethnicity | |||
| White | 4227 | 48.2 (46.8-49.7) | 0.05 |
| Black | 270 | 21.3 (18.8-23.9) | 0.02 |
| Hispanic | 370 | 22.7 (20.4-25.0) | 0.02 |
| Asian | 96 | 15.6 (12.5-18.8) | 0.02 |
| Other or unknown | 842 | 27.6 (25.7-29.5) | 0.03 |
| Income, $ | |||
| <49 000 | 915 | 32.4 (30.3-34.5) | 0.03 |
| 50 000-74 000 | 777 | 40.9 (38.0-43.7) | 0.04 |
| 75 000-99 000 | 760 | 46.0 (42.8-49.3) | 0.05 |
| ≥100 000 | 2010 | 49.9 (47.7-52.1) | 0.05 |
| Unknown | 1343 | 27.3 (25.8-28.7) | 0.03 |
| Educational level | |||
| Less than 12th grade | 11 | 15.0 (6.1-23.8) | 0.01 |
| High school diploma | 1017 | 31.3 (29.3-33.2) | 0.03 |
| Less than bachelor degree | 2879 | 41.5 (40.0-43.0) | 0.04 |
| Bachelor degree plus | 1285 | 49.3 (46.6-52.0) | 0.05 |
| Unknown | 612 | 24.9 (22.9-26.9) | 0.02 |
Table 3. Mean Annualized Prevalence of Granuloma Annulare in the United States (January 1, 2017, to December 31, 2018).
| Population | Granuloma annulare cases, No. | Prevalence per 100 000 (95% CI) | Prevalence, % |
|---|---|---|---|
| All granuloma annulare cases | 8930 | 58.3 (57.1-59.5) | 0.06 |
| Sex | |||
| Female | 6774 | 86.2 (84.1-88.3) | 0.09 |
| Male | 2157 | 28.9 (27.7-30.1) | 0.03 |
| Age, y | |||
| ≤19 | 468 | 19.1 (17.4-20.9) | 0.02 |
| 20-29 | 335 | 19.9 (17.7-22.0) | 0.02 |
| 30-39 | 647 | 33.4 (30.9-36.0) | 0.03 |
| 40-49 | 953 | 51.7 (48.4-55.0) | 0.05 |
| 50-59 | 1771 | 91.5 (87.3-95.8) | 0.09 |
| ≥60 | 4757 | 86.8 (84.3-89.3) | 0.09 |
| Race/ethnicity | |||
| White | 6370 | 72.7 (70.9-74.4) | 0.07 |
| Black | 388 | 30.7 (27.6-33.7) | 0.03 |
| Hispanic | 547 | 33.6 (30.8-36.4) | 0.03 |
| Asian | 126 | 20.5 (16.9-24.1) | 0.02 |
| Other or unknown | 1500 | 49.2 (46.7-51.7) | 0.05 |
| Income, $ | |||
| <49 000 | 1341 | 47.5 (44.9-50.0) | 0.05 |
| 50 000-74 000 | 1165 | 61.3 (57.8-64.8) | 0.06 |
| 75 000-99 000 | 1169 | 70.8 (66.8-74.9) | 0.07 |
| ≥100 000 | 3034 | 75.3 (72.6-78.0) | 0.08 |
| Unknown | 2221 | 45.1 (43.3-47.0) | 0.05 |
| Educational level | |||
| Less than 12th grade | 16 | 21.1 (10.6-31.6) | 0.02 |
| High school diploma | 1483 | 45.6 (43.3-47.9) | 0.05 |
| Less than bachelor degree | 4346 | 62.7 (60.8-64.5) | 0.06 |
| Bachelor degree plus | 1939 | 74.4 (71.1-77.7) | 0.07 |
| Unknown | 1148 | 46.7 (44.0-49.4) | 0.05 |
The incidence of granuloma annulare was higher among women (female to male ratio, 2.8:1; P < .001, determined by the χ2 test). The incidence of granuloma annulare was highest in the fifth decade of life, with an incidence of 58.6 (95% CI, 55.2-62.0) per 100 000 person-years among those 50 to 59 years of age compared with 34.6 (95% CI, 31.9-37.2) per 100 000 person-years among those 40 to 49 years of age and 23.1 (95% CI, 21.0-25.3) per 100 000 person-years among those 30 to 39 years of age (P < .001, determined by the χ2 test) (Table 2). The incidence of granuloma annulare was 2.3-fold higher among White individuals than Black individuals (48.2 [95% CI, 46.8-49.7] vs 21.3 [95% CI, 18.8-23.9]; P < .001, determined by the χ2 test). Incident granuloma annulare was more common among those with a higher household income and higher educational attainment.
Prevalent granuloma annulare was more common among women (female to male ratio, 3.0:1; P < .001, determined by the χ2 test). The prevalence of granuloma annulare was also highest in the fifth decade of life, with a prevalence of 91.5 (95% CI, 87.3-95.8) per 100 000 person-years among those 50 to 59 years of age compared with 51.7 (95% CI, 48.4-55.0) per 100 000 person-years among those 40 to 49 years of age and 33.4 (95% CI, 30.9-36.0) per 100 000 person-years among those 30 to 39 years of age (P < .001, determined by the χ2 test) (Table 3).
The prevalence of granuloma annulare was higher among White individuals (72.7 [95% CI, 70.9-74.4]) than Black (30.7 [95% CI, 27.6-33.7]), Hispanic (33.6 [95% CI, 30.8-36.4]), or Asian individuals (20.5 [95% CI, 16.9-24.1]) (P < .001, determined by the χ2 test) (Table 3). Prevalent granuloma annulare was more common among those with a higher household income and higher educational attainment.
Within 6 months of their first diagnosis, 4822 patients (41.5%) filled a prescription for a topical corticosteroid, and 1087 patients (9.4%) received an intralesional injection (Table 4). Within 6 months of their first diagnosis, oral tetracycline-class antibiotic prescriptions were filled by 820 patients (7.1%), and hydroxychloroquine prescriptions were filled by 268 patients (2.3%). The overall frequencies of treatment use remained similar at 12 months. Phototherapy, dapsone, systemic retinoids, and TNF inhibitors were rarely used.
Table 4. Medication and Procedures Used Among Patients With Granuloma Annulare in the United States.
| Medication or procedure | Patients, No. (%) | ||
|---|---|---|---|
| All (N = 11 608) | Seen by dermatologist at least once | ||
| Yes (n = 8339) | No (n = 3269) | ||
| Topical corticosteroid | |||
| Within 6 mo of diagnosis | 4822 (41.5) | 3602 (43.2) | 1220 (37.3) |
| Within 12 mo of diagnosis | 5278 (45.5) | 3947 (47.3) | 1331 (40.7) |
| Calcineurin inhibitor | |||
| Within 6 mo of diagnosis | 158 (1.4) | 138 (1.7) | 20 (0.6) |
| Within 12 mo of diagnosis | 197 (1.7) | 171 (2.1) | 26 (0.8) |
| Hydroxychloroquine | |||
| Within 6 mo of diagnosis | 268 (2.3) | 194 (2.3) | 74 (2.3) |
| Within 12 mo of diagnosis | 317 (2.7) | 233 (2.8) | 84 (2.6) |
| Oral tetracycline | |||
| Within 6 mo of diagnosis | 820 (7.1) | 644 (7.7) | 176 (5.4) |
| Within 12 mo of diagnosis | 1181 (10.2) | 909 (10.9) | 272 (8.3) |
| Dapsone | |||
| Within 6 mo of diagnosis | 40 (0.3) | 33 (0.4) | 7 (0.2) |
| Within 12 mo of diagnosis | 55 (0.5) | 47 (0.6) | 8 (0.2) |
| Systemic retinoid | |||
| Within 6 mo of diagnosis | 32 (0.3) | 28 (0.3) | 4 (0.1) |
| Within 12 mo of diagnosis | 45 (0.4) | 40 (0.5) | 5 (0.2) |
| Tumor necrosis factor inhibitor | |||
| Within 6 mo of diagnosis | 54 (0.5) | 41 (0.5) | 13 (0.4) |
| Within 12 mo of diagnosis | 62 (0.5) | 47 (0.6) | 15 (0.5) |
| Intralesional corticosteroid injection | |||
| Within 6 mo of diagnosis | 1087 (9.4) | 878 (10.5) | 209 (6.4) |
| Within 12 mo of diagnosis | 1381 (11.9) | 1119 (13.4) | 262 (8.0) |
| Phototherapy | |||
| Within 6 mo of diagnosis | 58 (0.5) | 49 (0.6) | 9 (0.3) |
| Within 12 mo of diagnosis | 91 (0.8) | 79 (0.9) | 12 (0.4) |
Patients rarely had encounters for other chronic inflammatory skin disorders for which these medications would be prescribed, such as acne (2.4% [282 of 11 608]), psoriasis (1.2% [143 of 11 608]), and atopic dermatitis (1.7% [198 of 11 608]), within 3 months before or after their first diagnosis of granuloma annulare.
Discussion
In this cross-sectional study using a large population-based data set, the annualized incidence of granuloma annulare is estimated to be 0.04%, and the annualized prevalence of granuloma annulare is estimated to be 0.06%. The findings of this study suggest that the prevalence of granuloma annulare in the community is approximately an order of magnitude less than what has been previously suggested in studies that have focused predominantly only on patients presenting to dermatology clinics.3,14,16,17
In this study, the incidence and prevalence of granuloma annulare were highest in the fifth decade of life, which is consistent with several prior studies suggesting that it is most commonly reported in the first 3 to 5 decades of life.3,4,21,22 However, there are a few small, single-center case series suggesting that granuloma annulare may also be common among children, although these studies lack a denominator, making it difficult to establish accurate incidence and prevalence estimates.5,9,17 Because the subcutaneous variant of granuloma annulare has been reported to be more common among children, it is also possible that these discrepancies may be associated with differences between granuloma annulare definitions used in each study.2,3
Similar to prior studies, a 3:1 female to male ratio of granuloma annulare was observed, suggesting that granuloma annulare is more common among women.3,5,14,15,16,17,23 In addition, granuloma annulare was more common among individuals with a higher income and higher educational attainment. Although granuloma annulare was more common among White individuals, it is only approximately 2-fold less common among Black, Hispanic, and Asian individuals, which has not previously been described, to our knowledge. These sociodemographic differences in the incidence and prevalence of granuloma annulare may reflect the underlying biology of granuloma annulare, although it is also important to consider the potential role of other factors, such as individual preferences to seek care or differences in access to care. Future population-based survey studies are needed to confirm the findings of this study based on claims data.24
Similar to prior work, the most commonly prescribed treatment of granuloma annulare was topical corticosteroids, with more than 40% of patients filling a prescription within 6 months of their first diagnosis.14 Intralesional corticosteroids and oral tetracyclines were also commonly used, with approximately 10% of patients being treated with these approaches. Although hydroxychloroquine has been suggested as a helpful treatment for granuloma annulare and other granulomatous conditions, it was rarely prescribed, with fewer than 3% of patients filling a prescription within 1 year of their diagnosis and oral tetracycline-class antibiotics being prescribed 3 times more frequently.1 Although further study is needed to understand the optimal treatment approaches for patients with granuloma annulare, given the effectiveness of hydroxychloroquine in other granulomatous conditions and its relatively favorable safety profile, hydroxychloroquine may represent an underused treatment for patients with granuloma annulare. Several small case series have suggested that hydroxychloroquine can be effective and would be valuable to explore in future randomized clinical trials.25,26,27 Although small studies have suggested that phototherapy and TNF inhibitors can be highly effective for patients with granuloma annulare, these modalities were rarely used, potentially owing to logistical and financial challenges limiting access to these off-label treatments.28,29,30
Limitations and Strengths
Our study has some limitations and should be interpreted in the context of its design. Given the commonly asymptomatic nature of granuloma annulare, some patients may not seek care, and our study population may be biased toward patients with more severe disease. As a result, our findings may underestimate the true incidence and prevalence of granuloma annulare in the community. Some clinicians may also choose not to use an ICD-10 code for granuloma annulare if it is a secondary concern. In addition, given the nature of claims data, it is not possible to evaluate differences between subtypes of granuloma annulare. However, given that at least 10% of patients received systemic treatments, it is likely that at least 10% of those in the study cohort had generalized disease. This result would be consistent with prior estimates that between 15% and 25% of patients with granuloma annulare present with generalized disease.3,4,5 Claims data also do not include detailed pathologic results for diagnostic confirmation, although the use of a validated approach to identify patients with granuloma annulare using ICD-10 codes alone reduces the risk of misclassification bias. However, this validation was conducted among a group of adult primary care and dermatology practices, and the results may not generalize to other settings, such as pediatric care. For instance, it is possible that subcutaneous granuloma annulare, which is more commonly reported in children, may not be captured effectively by our study design and that our estimates may underestimate the incidence and prevalence of granuloma annulare among children. Given the limitations of claims data, it is not possible to know whether filled prescriptions were for treatment of granuloma annulare or another disease, although several of the treatments (eg, acitretin and hydroxychloroquine) have few other common indications, and it was rare for patients to have an encounter for other chronic inflammatory diseases such as acne, psoriasis, and atopic dermatitis. Finally, sociodemographic data are not available for all patients in our data set. Future studies are needed to confirm our findings in other data sets and using other study designs, such as population-based surveys. A strength of this study is the use of a data set that is broadly representative of the US population to increase the generalizability of the results.
Conclusions
Granuloma annulare is a rare disease in the United States that is more common among women, middle-aged to older individuals, and White individuals. These findings provide important background regarding the basic epidemiology and overall burden of granuloma annulare in the United States. Future studies are needed to better understand the association of granuloma annulare with quality of life and the most optimal treatment approaches for this condition.
References
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