The association of anxiety with granuloma annulare: a case-control study of the National Institutes of Health 'All of Us' research programme.

Dear Editor, Granuloma annulare (GA) is an inflammatory skin disease that has been associated with diabetes, dyslipidaemia, hypothyroidism and autoimmune disorders.1,2 The annualized incidence and prevalence of GA in the USA are approximately 0.04% and 0.06%, respectively (with a female predominance).3 GA is clinically classified as localized (75% of cases), generalized or subcutaneous.4 There is a body of evidence supporting an association between several inflammatory dermatoses, such as psoriasis, and mental health conditions.5 Improvement of depression and anxiety following treatment of certain inflammatory dermatoses has also been described.5 It has been postulated that this association may, in part, relate to proinflammatory cytokines, which have been proposed to mechanistically connect inflammatory dermatoses and mental health conditions.6 A recent nested case-control study demonstrated a significant association of GA with depression, insomnia, opioid dependence and post-traumatic stress disorder.7 This study aims to investigate whether an association exists between GA and anxiety.

The Clinical Presentation and Comorbidities Associated with Granuloma Annulare in the Pediatric Population: A Retrospective Study.

Granuloma annulare (GA) is a cutaneous inflammatory disorder of unknown cause, typically characterized by an annular arrangement of dermal papules and nodules. While GA in adults has been linked to diabetes mellitus (DM) and other conditions, these associations have been less studied in children. A retrospective chart review was conducted of all pediatric patients diagnosed with GA at an urban academic institution over a 7-year period. A total of 47 patients were reviewed. Of these, 41 (85.1%) patients had localized GA, 3 (6.38%) had subcutaneous GA, 2 (4.26%) had generalized GA, and 1 (2.13%) had both localized and subcutaneous GA. The extremities were the most common site of involvement across all morphologies. Atopic conditions were determined in 23 (48.9%) patients, 16 (34.0%) of which had asthma, either alone or in conjunction with atopic dermatitis or allergic rhinitis. None of the patients carried a diagnosis of DM, and all 11 patients who were tested within 3 years of the documented visit had normal results. In summary, this retrospective series characterizes the presentation of pediatric GA and highlights a potential association with atopy. An association with DM was not observed.

Granuloma Annulare: An Updated Review of Epidemiology, Pathogenesis, and Treatment Options.

Granuloma annulare (GA) is an inflammatory granulomatous skin disease that can be localized (localized GA) or disseminated (generalized GA), with patch, perforating, and subcutaneous subtypes being less common variants of this benign condition. Recently, new research has emerged that further elucidates GA epidemiology and etiopathogenesis; importantly, new therapeutic options for GA have also been described, although there remains a paucity of randomized controlled studies. In this review, we summarize recent updates on GA epidemiology and etiopathogenesis and offer an updated review of the therapeutic options for GA currently reported in the literature. We hope that the current review galvanizes randomized controlled studies that will in turn help lead to the recommendation of evidence-based treatments for GA.

Incidence and Prevalence of Granuloma Annulare in the United States.

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.

Association of Granuloma Annulare With Type 2 Diabetes, Hyperlipidemia, Autoimmune Disorders, and Hematologic Malignant Neoplasms.

IMPORTANCE: Although granuloma annulare (GA) has been associated with several other conditions, these studies have been limited by single-center designs and small sample sizes. OBJECTIVE: To evaluate whether there is an association between GA and type 2 diabetes, hyperlipidemia, autoimmune conditions, and hematologic malignant neoplasms, using a large population-based cohort study. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study conducted between January 1, 2016, and June 30, 2019, used deidentified data from the US Optum Clinformatics Data Mart Database. A total of 5137 patients with GA were matched by age and sex with up to 10 randomly selected controls (n = 51 169) with a diagnosis of a nevus or seborrheic keratosis. MAIN OUTCOMES AND MEASURES: Logistic regression was used to evaluate for potential associations between GA and diabetes, hyperlipidemia, autoimmune conditions, and hematologic malignant neoplasms. All analyses were adjusted for race/ethnicity, income, and educational level. RESULTS: This study included 5137 individuals with GA (3760 women [73.2%]; mean [SD] age, 57.7 [19.0] years) and 51 169 controls (37 456 women [73.2%]; mean [SD] age, 57.7 [19.0] years). Those with GA were more likely than controls to have baseline diabetes (1086 [21.1%] vs 6780 [13.3%]; adjusted odds ratio [aOR], 1.67; 95% CI, 1.55-1.80), hyperlipidemia (1669 [32.5%] vs 14 553 [28.4%]; aOR, 1.15; 95% CI, 1.08-1.23), hypothyroidism (727 [14.2%] vs 5780 [11.3%]; aOR, 1.24; 95% CI, 1.15-1.36), and rheumatoid arthritis (62 [1.2%] vs 441 [0.9%]; aOR, 1.34; 95% CI, 1.02-1.75). Those with GA were more likely to have incident diabetes (144 [2.8%] vs 1061 [2.1%]; aOR, 1.31; 95% CI, 1.10-1.57), hypothyroidism (41 [0.8%] vs 252 [0.5%]; aOR, 1.59; 95% CI, 1.14-2.22), systemic lupus erythematosus (21 [0.4%] vs 65 [0.1%]; aOR, 3.06; 95% CI, 1.86-5.01), and rheumatoid arthritis (26 [0.5%] vs 122 [0.2%]; aOR, 2.05; 95% CI, 1.34-3.13). There was no association between GA and an increased risk of hematologic malignant neoplasms. CONCLUSIONS AND RELEVANCE: This population-based cohort study identified associations between GA and baseline diabetes and hyperlipidemia as well as between GA and both baseline and incident autoimmune conditions. These findings suggest that diabetes and hyperlipidemia may be risk factors for the development of GA and that autoimmunity may be an important factor in the pathogenesis of GA.

Subcutaneous granuloma annulare on the heel: A case report and review of the Japanese published work.

Subcutaneous granuloma annulare is a rare variant of granuloma annulare. It mostly presents as painless subcutaneous nodule(s) with or without annular lesions on the lower legs and scalp of children. We herein report a case of a 5-year-old Japanese girl with subcutaneous granuloma annulare on the right heel. The lesions improved in 15 months without any therapy. We also review 85 reported cases of subcutaneous granuloma annulare between 1 and 85 years of age in the Japanese published work. The most susceptible age was 5 years and below; however, a small peak occurred from the 40s to 60s. Subcutaneous granuloma annulare was more frequent in females (male : female ratio, 6:11). Sixty-five cases (76.4%) had multiple lesions; the average number of lesions was 4.8 ± 5.8. The most affected site was the lower legs (28 cases), followed by the dorsum of the foot (21 cases) and scalp (17 cases). The heel was an unusual location; only two cases of sole subcutaneous granuloma annulare have been reported. Twenty-one cases revealed a classical dermal change along with a subcutaneous change. Patients with classical dermal lesions were younger (P < 0.0001) and had a smaller number of lesions (P < 0.05) than those without the lesions. The lesion(s) resolved in 24 of the 44 untreated cases within 1 week to 19 months. Refractory or recurrent lesion(s) were seen in four of 21 treated cases and in four of 44 untreated cases. Because subcutaneous granuloma annulare lesions often resolve spontaneously without treatment, invasive treatments should be avoided.

[Generalized granuloma annulare: A clinicopathological study]. / Granulome annulaire généralisé : étude anatomoclinique.

BACKGROUND: Granuloma annulare (GA) is a benign granulomatous skin disorder that is generalized (GGA) in 15 % of cases. Although many case reports describe a relationship between GGA and systemic diseases, few large series have been published, and their association is debated. We present herein a series of GGA in order to describe their clinical and histological features. PATIENTS AND METHODS: We included all biopsy-proven cases of GA presenting at the dermatopathology laboratory of Strasbourg where generalized (i.e. over 10 lesions). Clinical features were obtained from patients' medical files. RESULTS: We included 35 GGA, with a sex ratio of 0.5. The mean age was 54 years. Lesions were annular or non-annular in equal measure and were symptomatic in 25 % of cases. Most patients (77 %) had an associated disease, already known in 60 % of cases, including dyslipidemia (27 %), diabetes mellitus (20 %), immunosuppressive drugs (17 %), atopy (17 %), auto-immune disease (17 %), hematological disease (14 %), and cancer (9 %). Histological analysis revealed the predominant pattern to be interstitial (54 %) rather than palisading (20 %), having no correlation with clinical type. Eosinophils were frequent (46 %) in GA but were not correlated with systemic disease or drug taking. Among the 40 % of patients treated, 50 % had a successful outcome on topical corticosteroids, doxycycline, antimalarial drugs or phototherapy. DISCUSSION: GGA differs from localized GA, which is mostly associated with an already known systemic disease, whether metabolic, infectious or neoplastic, uncorrelated with clinical or histological features, and screening is necessary.

Granuloma annulare: a retrospective series of 133 patients.

Although granuloma annulare (GA) is a relatively common dermatologic condition, little is known about its epidemiology and pathogenesis. Additionally, there is conflicting evidence regarding its association with other diseases. In our retrospective study, we attempted to determine the number of cases of GA seen annually at a large academic center and clarify disease associations with GA. We utilized PennSeek, a tool developed by the Penn Medicine Data Analytics Center to search electronic medical records (EMRs), to identify all cases of GA seen at the University of Pennsylvania (Philadelphia, Pennsylvania) from 2008 to 2014. All biopsy-proven cases of GA from 2010 to 2014 were reviewed for medical comorbidities, medications, treatments, and outcomes. On average, the percentage of patients given a diagnosis of GA annually was 0.22%. There were 133 cases of biopsy-proven GA that were reviewed. The findings solidify our understanding of the epidemiology of GA and diseases that can be associated with GA.

Advances in Inflammatory Granulomatous Skin Diseases.

Inflammatory granulomatous dermatitides include cutaneous sarcoidosis, necrobiosis lipoidica, granuloma annulare, and reactive granulomatous dermatitis. The etiopathogenesis of these disorders is not well understood; but the T helper 1 response mediated by interferon-gamma, tumor necrosis factor-alpha, and interleukin (IL) 1, 2, and 6 and the T helper 17 response mediated by IL-17 play a role. These inflammatory granulomatous disorders often have cutaneous manifestations in addition to extracutaneous manifestations or associations with systemic diseases. The authors review these disorders, propose diagnostic and evaluative approaches to these diseases, and explore recent literature with regard to the etiopathogenesis and treatment of these entities.