Causes of Oral Granulomatous Disorders: An Update and Narrative Review of the Literature.

Granulomatous diseases include a diverse range of chronic inflammatory disorders with a wide variety of pathologies and clinical characteristics. In particular, the orofacial region can be affected by granulomatous conditions-whether as an isolated disease or as part of a systemic disorder. Regardless of the nature of the disease or its mechanism of development, precise diagnosis can be challenging, as etiopathogenesis may be driven by several causes. These include reactions to foreign bodies, infections, immune dysregulation, proliferative disorders,, medications, illicit drugs, and hereditary disorders. Granulomas can be identified using histopathological assessment but are not pathognomonic of a specific disease, and therefore require correlation between clinical, serological, radiographical, and histopathological findings. The purpose of this review is to provide a summary of the etiopathogenesis, clinical and histopathologic characteristics, and treatment of oral granulomatous disorders.

Dermoscopy of cutaneous granulomatous disorders: A study of 107 cases.

BACKGROUND: Cutaneous granulomatous disorders (CGDs) can share some features, but an accurate assessment of various findings and their pattern can be useful in differentiating them. In addition to common dermoscopic findings for CGDs, some peculiar dermoscopic characteristics can be helpful in distinguishing them. OBJECTIVE: Herein, we aimed to evaluate dermoscopic findings in patients with CGDs and determine the dermoscopic criteria that could suggest the type of granulomatous disorder. MATERIAL AND METHODS: A total of 107 cases including 75 (70.09%) males and 32 (29.90%) females with an established diagnosis of cutaneous leishmaniasis (n = 49), cutaneous sarcoidosis (n = 23), granuloma annulare (GA) (n = 18), and tattoo granuloma (n = 17) confirmed by clinical and pathological studies were included. Based on the previous studies available in the literature, we wrote a checklist containing dermoscopic features of CGDs. Afterward, two dermatologists independently reviewed all dermoscopic images for the presence or absence of each item on the checklist. Descriptive analysis, fisher exact, chi-square, and t-test were used. The granulomatous disorders with larger sample sizes were selected for further analysis, including the univariate and conditional multivariate logistic regressions. RESULTS: The most prevalent nonvascular findings in all of our CGD patients were white scaling (N = 67%, 62.61%), diffuse or localized orange structureless areas (N = 53%, 49.53%), and diffuse erythema (N = 48%, 44.85%). Furthermore, the most frequent vascular findings in all of our CGD cases were branching and arborizing vessels (N = 30%, 28.03%), linear irregular (N = 30%, 28.03%), and dotted vessels (N = 27%, 25.23%). CONCLUSION: For differentiating leishmaniasis from sarcoidosis by dermoscopy, white scaling and white scarring areas are more suggestive of cutaneous leishmaniasis, whereas the presence of arborizing vessels would be more in favor of sarcoidosis. When comparing GA to cutaneous leishmaniasis, the latter significantly shows more linear irregular vessels, hairpin vessels, white scaling, and white scarring areas. In the case of differentiating sarcoidosis from GA, the presence of hairpin vessels would be suggestive of sarcoidosis.

Lactotroph PitNET/adenoma associated to granulomatous hypophysitis in a patient with Crohn's disease: A case report.

Granulomatous hypophysitis is a rare and poorly understood condition. Although certain cases are treated as primary pituitary autoimmune disorders, rare cases may be associated with pituitary neuroendocrine tumours (PitNETs) and systemic inflammatory diseases. Here, we report a case of a 47-year-old man that underwent endoscopic trans-sphenoidal excision of a pituitary mass diagnosed as PitNET. On histologic evaluation, the neoplasm showed an admixture of granulomas with extensive inflammatory infiltrate and lactotroph PitNET/adenoma. Careful anamnestic examination revealed a diagnosis of Crohn's disease 20 years prior. Although rarely done, both PitNET and Crohn's disease may be associated with granulomatous hypophysitis, and our patient had both conditions. During the 6-year follow-up, PitNETs and hypophysitis did not recur, while Crohn's disease was only partially controlled by medical therapy. To our knowledge, this is the first description of association of granulomatous hypophysitis, PitNET and Crohn's disease.

Mastitis granulomatosa asociada a eritema nudoso: estudio de 42 casos / Granulomatous mastitis associated with erythema nodosum: A case series of 42 patients

Introducción:La mastitis granulomatosa (MG) se define por la presencia de inflamación granulomatosa en el tejido mamario. El eritema nudoso (EN) es una paniculitis inflamatoria reactiva caracterizada por nódulos subcutáneos dolorosos en las extremidades inferiores. La asociación entre MG y EN ha sido descrita, pero está poco estudiada. Nuestro objetivo fue analizar las características clínicas de las pacientes diagnosticadas de MG en nuestro centro y su asociación con EN.Métodos:Se revisaron retrospectivamente los casos diagnosticados histológicamente de MG entre 1995 y 2020.Resultados:Cuarenta y dos mujeres fueron diagnosticadas de MG. La edad media al diagnóstico fue de 41,619años y el 59,5% tenían ascendencia sudamericana. El EN se asoció con MG en el 11,9% de las pacientes. Las pacientes con EN fueron diagnosticadas precozmente respecto a aquellas con MG aislada (0,4meses frente a 6,81; p<0,05). La ulceración en la MG fue más prevalente en pacientes con EN asociado (60% vs 14,7%; p<0,05).Conclusión:El EN en pacientes con GM puede facilitar el diagnóstico precoz de esta rara condición que imita el cáncer de mama.(AU)

Background:Granulomatous mastitis (GM) is defined by the formation of granulomatous inflammation in breast tissue. Erythema nodosum (EN) is a reactive inflammatory panniculitis characterized by erythematous subcutaneous nodules in the lower limbs. The association of GM with EN has been rarely reported. Our aim was to retrospectively review our series of patients with GM to better characterize their features and their association with EN.Methods:Cases histologically diagnosed as granulomatous inflammation in breast tissue between 1995 and 2020 were retrospectively reviewed.Results:Forty-two women were diagnosed with GM. The average age at diagnosis was 41.619years, and 59.5% were of South-American ethnicity. EN was associated with GM in 11.9% of the patients. Patients with EN were diagnosed earlier than isolated GM (0.4months vs 6.81months; P<.05). Ulceration in the GM was more prevalent in patients with associated EN (60% vs 14.7%; P<.05).Conclusion:EN in patients with GM may reduce the evolution time and may help to diagnose this rare condition that mimics breast carcinoma. (AU)

[Granulomatous mastitis associated with erythema nodosum: A case series of 42 patients]. / Mastitis granulomatosa asociada a eritema nudoso: estudio de 42 casos.

BACKGROUND: Granulomatous mastitis (GM) is defined by the formation of granulomatous inflammation in breast tissue. Erythema nodosum (EN) is a reactive inflammatory panniculitis characterized by erythematous subcutaneous nodules in the lower limbs. The association of GM with EN has been rarely reported. Our aim was to retrospectively review our series of patients with GM to better characterize their features and their association with EN. METHODS: Cases histologically diagnosed as granulomatous inflammation in breast tissue between 1995 and 2020 were retrospectively reviewed. RESULTS: Forty-two women were diagnosed with GM. The average age at diagnosis was 41.619years, and 59.5% were of South-American ethnicity. EN was associated with GM in 11.9% of the patients. Patients with EN were diagnosed earlier than isolated GM (0.4months vs 6.81months; P<.05). Ulceration in the GM was more prevalent in patients with associated EN (60% vs 14.7%; P<.05). CONCLUSION: EN in patients with GM may reduce the evolution time and may help to diagnose this rare condition that mimics breast carcinoma.

Dermatoscopy of Cutaneous Granulomatous Disorders.

Cutaneous granulomatous disorders represent diseases with underlying granulomas on histology and are broadly divided into infectious and noninfectious disorders. Although histology is sine qua non in diagnosis of granulomatous disorders, lately dermoscopy has come up as a useful tool assisting in diagnosis of granulomatous disorder. Dermoscopy of granulomatous disorder is characterized by localized or diffuse, structureless yellowish-orange areas, along with vessels. Dermoscopic features of granulomatous disorders can be overlapping among various disorders, but detailed accurate assessment of various findings and their pattern may be useful in differentiating among them. In addition to this, peculiar dermatoscopic findings seen can also prove useful in distinguishing between various disorders. Hereby, we discuss dermatoscopic findings of various granulomatous disorders.

Necrobiosis lipoidica-like lesions in a nondiabetic patient with systemic sarcoidosis: A case report and review of the literature.

Necrobiosis lipoidica-like lesions, in known cases of sarcoidosis, can be considered as a member of the broad spectrum of histologic changes in sarcoidosis.

Incidence and Presentation of Sarcoidosis With and Without HIV Infection.

BACKGROUND: Case reports describe incident sarcoidosis in persons with HIV (PWH). The association between HIV and risk of sarcoidosis, and differences in presentation in PWH, have not been systematically assessed. METHODS: Subjects were selected from the Veterans Aging Cohort Study (VACS), a longitudinal cohort study including veterans with HIV and matched uninfected veterans. This was a prospective observational analysis in which we evaluated both the incidence (via incidence rate ratio) and presentation and treatment (by comparison of rates of organ involvement and use of medications) of sarcoidosis in PWH compared with HIV-negative controls. We also assessed risk factors (via Cox regression) associated with the development of sarcoidosis including CD4 count and viral load trajectory. RESULTS: Of 1614 patients evaluated via chart review, 875 (54%) had prevalent sarcoidosis and 325 (20%) had confirmed incident sarcoidosis. Incident sarcoidosis occurred in 59 PWH and 266 uninfected. The incidence of sarcoidosis was lower in PWH than uninfected (incidence rate ratio [IRR], 0.61; 95% CI, 0.46-0.81) and especially low in patients with unsuppressed viremia (IRR, 0.04; 95% CI, 0.02-0.08) compared with uninfected). At diagnosis of sarcoidosis, the median CD4 count among PWH was 409 cells/mm3; 77% had HIV-1 RNA <500 copies/mL. No significant differences were observed between PWH and uninfected in terms of organ involvement, disease severity, or use of oral glucocorticoids. CONCLUSIONS: HIV, particularly with persistent viremia, was associated with decreased risk of incident sarcoidosis; severity and treatment were similar between PWH and uninfected.

Comorbidities Associated with Granuloma Annulare: A Cross-Sectional, Case-Control Study.

Background: Granuloma annulare (GA) is a cutaneous granulomatous disorder of unknown etiology. There are conflicting data on the association between GA and multiple systemic conditions. As a result, we aimed to clarify the reported associations between GA and systemic conditions. Methods: A retrospective, cross-sectional, case-control study was performed in which the medical records of biopsy-confirmed GA patients ≥18 years of age, who presented to the Johns Hopkins Hospital System between 1 January 2009 and 1 June 2019, were reviewed. GA patients were compared to controls matched for age, race, and sex. Results: After adjusting for confounders, GA patients (n = 82) had higher odds of concurrent type II diabetes (odds ratio (OR) = 5.27; 95% confidence interval (CI), 1.73-16.07; p < 0.01), non-migraine headache (OR = 8.70; 95% CI, 1.61-46.88; p = 0.01), and a positive smoking history (OR = 1.93; 95% CI, 1.10-3.38; p = 0.02) compared to controls (n = 164). Among GA patients, women were more likely to have ophthalmic conditions (p = 0.04), and men were more likely to have cardiovascular disease (p < 0.01) and type II diabetes (p = 0.05). No differences in systemic condition associations were observed among GA subtypes. Conclusions: Our results support the reported association between GA and type II diabetes. Furthermore, our findings indicate that GA may be associated with cigarette smoking and non-migraine headache disorders.

Sarcoidosis in Jordan: A Study of the Clinical Phenotype and Disease Outcome.

OBJECTIVES: This study aims to evaluate the clinical phenotypic features of sarcoidosis in a single-center academic hospital in Jordan. PATIENTS AND METHODS: A retrospective file review was performed at an academic medical center in Jordan that included all patients diagnosed with sarcoidosis between January 2000 and December 2018. A total of 150 patients with sarcoidosis (38 males, 112 females; mean age 47.8±11.7 years; range, 17 to 79 years) were evaluated. Clinical data extracted from the files included the sex of the patient, the age at time of diagnosis, diagnosis date, the season during which the diagnosis was established, and smoking history. Biopsy histopathology, spirometry, nerve conduction, echocardiography, and imaging reports including plain radiographs, ultrasonographic, magnetic resonance and computed tomography reports were reviewed. Data including laboratory values, medication usage, clinical outcomes, and morbidity/mortality were collected. Pulmonary function tests including spirometry and lung volumes along with the diffusing capacity for carbon monoxide were reviewed for the presence of restriction, obstruction or reduction in the diffusion capacity of carbon monoxide. Identification of extra-thoracic organ involvement was determined in each patient in accordance with the criteria suggested by the updated World Association of Sarcoidosis and Other Granulomatous Disorders. RESULTS: A total of 77.3% of the patients were diagnosed by biopsy. One case of Lofgren's syndrome was identified. Of the patients, 18.0% had isolated pulmonary sarcoidosis, 75.3% had pulmonary and extra-pulmonary sarcoidosis and 6.7% had isolated extra-pulmonary sarcoidosis while 81.3% had respiratory symptoms, mostly shortness of breath and cough. Extra-thoracic organ involvement mostly involved the musculoskeletal system (33%) followed by the skin (20%). Female patients had more extra-thoracic involvement but the sex difference was only statistically significant for cutaneous involvement. Of the patients, 84% received treatment while 20% had disease remission during the first two years after diagnosis and 70% required treatment beyond two years after diagnosis. CONCLUSION: Various sarcoidosis clinical phenotypes are seen among Jordanian patients. Jordanian females are more affected by the disease and have more extra-thoracic involvement compared to male patients. A large number of the study patients received treatment.

Clinical Manifestations, Diagnosis, and Treatment of Sarcoidosis.

The focus of this review is current knowledge about the epidemiology, clinical manifestations, diagnosis, and treatment of both pulmonary sarcoidosis and extrapulmonary sarcoidosis. Although intrathoracic involvement is the hallmark of the disease, present in over 90% of patients, sarcoidosis can affect virtually any organ. Clinical presentations of sarcoidosis are diverse, ranging from asymptomatic, incidental findings to organ failure. Diagnosis requires the presence of noncaseating granuloma and compatible presentations after exclusion of other identifiable causes. Spontaneous remission is frequent, so treatment is not always indicated unless the disease is symptomatic or causes progressive organ damage/dysfunction. Glucocorticoids are the cornerstone of treatment of sarcoidosis even though evidence from randomized controlled studies is lacking. Glucocorticoid-sparing agents and biologic agents are often used as second- and third-line therapy for patients who do not respond to glucocorticoids or experience serious adverse effects.

Ultrasound imaging of abdominal sarcoidosis: State of the art.

Since it has been recognized that sarcoidosis (SA) is not an exclusive disorder of the lungs but can also affect other organs such as the liver and spleen, efforts have been made to define specific imaging criteria for the diagnosis of the single organ involvement, and the concept has been reinforced that the exclusion of alternative causes is important to achieve the correct diagnosis. Ultrasound (US) is a useful tool to evaluate patients with suspected abdominal SA, such as of the liver, spleen, kidney, pancreas and other organs, showing findings such as organomegaly, focal lesions and lymphadenopathy. While the diagnosis of abdominal SA is more predictable in the case of involvement of other organs (e.g., lungs), the problem is more complex in the case of isolated abdominal SA. The recent use of contrast-enhanced ultrasound and endoscopic ultrasound elastography has provided additional information about the enhancement patterns and tissue rigidity in abdominal SA. Here we critically review the role of US in abdominal SA, reporting typical findings and limitations of current evidence and by discussing future perspectives of study.

Dermatoscopy of Granulomatous Disorders.

Although diagnosis of cutaneous granulomatous disorders (CGDs) is usually suspected based on morphologic findings, localization, and anamnestic data, clinical differentiation from each other and from similar dermatoses may be challenging. Recently, dermatoscopy has been demonstrated to be a useful tool for assisting the recognition of several CGDs. This article provides a current overview of the dermatoscopic features of the main noninfectious and infectious CGDs, including sarcoidosis, necrobiosis lipoidica, granuloma annulare, rheumatoid nodules, and leishmaniasis. Other, less common, CGDs are briefly addressed, including granulomatous rosacea, acne agminata, and leprosy.

A granulomatous conundrum: Concurrent necrobiosis lipoidica, cutaneous sarcoidosis and erythema nodosum in a nondiabetic patient.

Necrobiosis lipoidica (NL) and cutaneous sarcoidosis are granulomatous disorders with a largely unknown aetiopathogenesis. Evidence of co-existing NL and sarcoidosis in the same patient may suggest a degree of overlap between these entities through shared granulomatous inflammatory pathways. Occasionally, one condition can mimic the other, making their distinction difficult. We report a novel case of a non-diabetic woman who presented with concurrent NL, cutaneous sarcoidosis and erythema nodosum. We discuss some of the complexities distinguishing these entities and propose that they may represent different stages of the same granulomatous process linked through yet unknown pathomechanisms.

Calcitriol-mediated hypercalcemia secondary to granulomatous disease caused by soft-tissue filler injection: a case report.

Soft-tissue filler (STF) injections have been used worldwide for cosmetic reasons. In most cases, they are not approved by the United States Food and Drug Administration (FDA). Regulatory boards in Latin American countries do not allow the medical use of STF injections; however, these injections are still widely used. A case of calcitriol-mediated hypercalcemia with ectopic calcifications, chronic kidney disease, nephrolithiasis and calcinosis is presented. The reported case highlights the consequences of STF use, including calcitriol-mediated hypercalcemia secondary to granulomatous reactions years after an esthetic procedure.