Cutaneous Crohn disease presenting as "knife-edged" ulcers: a case report.

BACKGROUND: CCD presents as non-caseating granulomas within the skin at a site distant from the GI tract. CCD is a debilitating extraintestinal sequela of CD that can sometimes precede its GI manifestations. In the absence of GI symptoms, the histopathologic and clinical features of CCD can present as a variety of inflammatory skin conditions that can range from ruptured follicle-associated granulomas to cutaneous ulcerations. While a variety of therapeutic options for patients with CCD and concurrent luminal CD have been described in the literature, there is no standard treatment algorithm for the management of refractory CCD with limited or covert GI involvement. CASE REPORT: The authors discuss the case of a 33-year-old female who presented to the wound care clinic with multiple "knife-edged" cutaneous ulcerations involving the intertriginous spaces, found to be consistent with CCD. Her original cutaneous symptoms and diagnosis manifested with minimal GI involvement and responded to IVIG treatment. CONCLUSIONS: This case supports the inclusion of CCD in the differential diagnosis in patients with knife-edged granulomatous skin lesions in intertriginous locations. This clinical condition may present in the setting of no or limited GI symptoms. The management of CCD and a proposed treatment algorithm are also presented.

Efficacy Of Common Salt Application On The Umbilical Granuloma In Infants.

The objective of this study was to determine the efficacy of the application of common plain salt for the treatment of umbilical granuloma in infants. The study design was descriptive case series and was conducted over a period of 12 months at the paediatric unit, Mardan Medical Complex, Mardan, Pakistan. For this study a total of 50 infants with clinically evident umbilical granuloma were selected. Application of a pinch of common plain salt was advised on the granuloma twice a day for three consecutive days. Outcomes in the shape of complete resolution of the granuloma, adverse effects, and recurrence of granuloma were assessed. The number of patients responding well to the treatment was 45 (90%). The treatment showed good response and there was not any adverse effect or recurrence. It was concluded that the common plain salt is a simple, effective, safe, and cheaper option for the treatment of umbilical granuloma in infants.

A comparison of radiofrequency Coblation and cold steel excision in the treatment of idiopathic vocal process granulomas.

OBJECTIVE: To compare the effectiveness of radiofrequency Coblation assisted excision and cold steel excision in the treatment of idiopathic vocal process granulomas. METHODS: A retrospective study was performed of patients with idiopathic vocal process granulomas who underwent radiofrequency Coblation excision or cold steel excision between January 2013 and January 2020. The recurrence rate was compared among the two groups at six months post-operatively. RESULTS: Of the 47 patients with vocal process granulomas, 28 were in the cold steel excision (control) group and 19 were in the Coblation-assisted group. The recurrence rate in the control group was significantly higher than that in the Coblation-assisted group (60.7 per cent vs 5.3 per cent; p < 0.001). In addition, the voice recovery of the Coblation-assisted group was significantly better than that of the control group; vocal quality recovered one month after surgery in the Coblation-assisted group. CONCLUSION: Radiofrequency Coblation should be considered the optimal method when approaching idiopathic vocal process granulomas surgically.

Evaluación de la incidencia, factores predictivos y consideraciones sobre el tratamiento de los granulomas genitourinarios asintomáticos después de la terapia intravesical con bacilo de Calmette-Guérin / Evaluation of incidence and predictive factors, and treatment considerations for asymptomatic genitourinary granulomas after intravesical bacillus Calmette-Guérin therapy

Introducción y objetivos Aunque las complicaciones de la terapia intravesical con el bacilo de Calmette-Guérin (BCG) están bien descritas, pocas veces se ha comunicado la formación posterior de granulomas genitourinarios asintomáticos, y su estrategia de tratamiento sigue siendo controvertida. El objetivo de este estudio es evaluar la tasa de incidencia de la formación de granulomas genitourinarios asintomáticos que imitan la recurrencia del cáncer de vejiga tras el tratamiento intravesical con el BCG, así como identificar las estrategias de diagnóstico y tratamiento según las características de los pacientes. Pacientes y métodos Se realizó una revisión retrospectiva de 162 pacientes sometidos a terapia intravesical con BCG. En los pacientes que desarrollaron granulomas, se evaluó el intervalo de tiempo entre la instilación de BCG y el desarrollo del granuloma, la presencia de bacterias acidorresistentes en las muestras de patología, los resultados del cultivo/reacción en cadena de la polimerasa, las estrategias de tratamiento de las lesiones y los resultados clínicos. Resultados Se desarrollaron masas genitourinarias asintomáticas en 14 pacientes, de los cuales 5 se sometieron a evaluaciones histológicas confirmando en todos los casos una inflamación granulomatosa. Los órganos afectados fueron el riñón, la vejiga, la próstata y el pene. Aunque 5 de los 5 pacientes no recibieron tratamiento para los granulomas, a uno de ellos se le administró medicación antituberculosa para evitar el empeoramiento de la lesión durante el periodo perioperatorio de la cistoprostatectomía programada. Ninguno de los pacientes experimentó empeoramiento o recurrencia de las lesiones granulomatosas. Los pacientes que desarrollaron masas asintomáticas (n=14) eran significativamente más jóvenes que ...(AU)

Introduction and objectives Although the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions.Patients and methods A retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes. Results Asymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n=14) were significantly younger than those who did not (P=.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (P=.032); however, none of the parameters were associated with histologically confirmed granuloma formation...(AU)

Cutaneous Sarcoidosis.

Sarcoidosis is a chronic, multisystem, inflammatory disorder that is characterized by noncaseating granulomas that cause organ dysfunction with various clinical subphenotypes. The incidence and prevalence of sarcoidosis varies greatly by ethnic background. There are significant racial disparities in prevalence, severity, and outcomes; however, there is a dearth of studies investigating the impact of structural racism. The skin is often the presenting and second most frequently involved organ with significant implications on diagnosis and management in patients with darkly pigmented skin. Workup should be comprehensive given the multisystem involvement. There are many therapies for sarcoidosis, although none is universally effective.

Sarcoidosis.

Sarcoidosis is a disease of unknown cause characterized by granulomatous inflammation. Although the lung is almost universally involved, any organ can be affected. Complex pathogenesis and protean clinical manifestations are additional features of the disease. The diagnosis is one of exclusion, although the presence of noncaseating granulomas at disease sites is a prerequisite in most cases. The management of sarcoidosis requires a multidisciplinary approach, particularly when the heart, the brain, or the eyes are involved. The paucity of effective therapies and the lack of reliable predictors of disease behavior greatly contribute to making sarcoidosis a challenging disease to manage.

Can vocal process granuloma location forecast the efficacy of anti-reflux treatment?

OBJECTIVE: The objective of this study was to evaluate the efficacy of anti-reflux therapy on the idiopathic vocal process granulomas. METHOD: This was a prospective case series study. The patients with vocal process granulomas who met the inclusion criteria were analysed. Proton pump inhibitors and vocal hygiene education were conducted for 8-20 weeks. RESULTS: Of the 16 patients with vocal process granulomas, 5 (31.25 per cent) patients achieved complete remission. The complete remission rate of granulomas was not significantly related to age (p = 1.000), sex (p = 0.296), side (p = 0.299), position (p = 0.100), endoscopic morphology (p = 0.263) or proton pump inhibitor treatment course (p = 0.543) but was significantly associated with granuloma location (p = 0.001) and granuloma size (p = 0.012). CONCLUSION: Granulomas in the vocal cord and the margin of the vocal process had an excellent response to proton pump inhibitors, but granulomas on the surface of vocal process and arytenoid cartilage body had little response to proton pump inhibitors. The prolonged period of proton pump inhibitor treatment did not increase the complete remission rate of vocal process granulomas.

[Sarcoidosis as prime example of a granulomatous disease]. / Sarkoidose als Paradebeispiel einer granulomatösen Erkrankung.

Sarcoidosis is the most frequent immunologically related granulomatous disease and can serve as a model for understanding diseases within this category. The evidence on the diagnostics and treatment is so far limited. It is therefore all the more important that two new and significant guidelines on diagnosis and treatment of sarcoidosis were published during the last 2 years. Additionally, there were more new publications, which were considered for this review article. In this context, this review article provides a current update and overview of sarcoidosis. Pathophysiologically, there is an increasing understanding of the complex processes and interactions involved in the inflammatory processes and granuloma formation. The probability of a diagnosis of sarcoidosis is determined by compatible histology, the exclusion of differential diagnoses and if possible evidence of a multiorgan manifestation. The clinical course is variable and ranges from an asymptomatic manifestation to severe life-threatening organ failure. The most frequently affected organ are the lungs. Pulmonary fibrosis is the most severe form and is also decisive for mortality. An increasing focus is on the extrapulmonary organ manifestations, in particular, cardiac, hepatosplenic, gastrointestinal, renal, ocular and neurological involvement. Treatment, which consists primarily of immunosuppression, should be initiated in cases of organ-threatening or quality of life-impairing activity of the disease. Additional organ-specific management must also be evaluated. In cases of organ failure transplantation should be considered. Due to the limited evidence especially for the treatment of multiorgan sarcoidosis, when possible, patients with this disease should be included in clinical trials.

Granulomatous Diseases of the Central Nervous System.

PURPOSE OF REVIEW: To discuss the pathophysiology, key clinical features, necessary diagnostic evaluation, and current treatment regimens for granulomatous diseases of the central nervous system. RECENT FINDINGS: The diagnosis and management of granulomatous disease of the central nervous system has been revolutionized by advances in diagnostic imaging. Nevertheless, tissue and/or cerebrospinal fluid (CSF) sampling remains necessary to establish the diagnosis in most cases. Establishing a specific diagnosis is critical because treatment selection needs to focus on the granulomatous process centering on either antibiotic or immunosuppressive agents. Particular for non-infectious granulomatous disease more aggressive immunotherapies may help in clinical outcome. There are multiple non-infectious and infectious etiologies for granulomatous disease of the central nervous system. Clinical manifestations result from local structural invasion of granulomas or granulomatous inflammation of the blood vessels and meninges. Rapid diagnosis and specific treatment is essential.

Targeting Molecular Inflammatory Pathways in Granuloma as Host-Directed Therapies for Tuberculosis.

Globally, more than 10 million people developed active tuberculosis (TB), with 1.4 million deaths in 2020. In addition, the emergence of drug-resistant strains in many regions of the world threatens national TB control programs. This requires an understanding of host-pathogen interactions and finding novel treatments including host-directed therapies (HDTs) is of utter importance to tackle the TB epidemic. Mycobacterium tuberculosis (Mtb), the causative agent for TB, mainly infects the lungs causing inflammatory processes leading to immune activation and the development and formation of granulomas. During TB disease progression, the mononuclear inflammatory cell infiltrates which form the central structure of granulomas undergo cellular changes to form epithelioid cells, multinucleated giant cells and foamy macrophages. Granulomas further contain neutrophils, NK cells, dendritic cells and an outer layer composed of T and B lymphocytes and fibroblasts. This complex granulomatous host response can be modulated by Mtb to induce pathological changes damaging host lung tissues ultimately benefiting the persistence and survival of Mtb within host macrophages. The development of cavities is likely to enhance inter-host transmission and caseum could facilitate the dissemination of Mtb to other organs inducing disease progression. This review explores host targets and molecular pathways in the inflammatory granuloma host immune response that may be beneficial as target candidates for HDTs against TB.

Laser in the Treatment of Granulomas on the Nose Produced by Polymethylmethacrylate: A Case Series.

BACKGROUND: The search for aesthetic non-surgical procedures is growing. The use of polymethylmethacrylate (PMMA) as a filling material in the nose represents one of the many options among these aesthetic procedures. Its use, however, can lead to complications. The treatment of these complications is often challenging. METHODS: We performed a retrospective clinical analysis of the medical records of patients undergoing treatment of PMMA granulomas of the nose at a private clinic from January, 2015, to January, 2021. A short-pulsed neodymium-YAG (Nd:YAG) laser was applied intranasally or directly by cutaneous incision in the granulomas. Laser-tissue interaction heats the alloplastic material, fragments the product and creates cleavage paths, thereby facilitating the removal of PMMA, either by intercartilaginous removal or aspiration. RESULTS: Twenty-seven patients were included in the study. All had a history of PMMA injection in the nose. All patients were treated with an intralesional pulsed 1064nm Nd:YAG laser. The material removed after laser-tissue interaction was sent for histopathological examination; this showed the presence of microparticles of exogenous material compatible with PMMA. The partial removal of the alloplastic material was shown to be effective in all cases. One patient developed a small blister in the nasal dorsum. Follow-up ranged from six to 47 months. CONCLUSIONS: The use of intralesional Nd:YAG laser for the treatment of PMMA granulomas on the nose proved to be an effective and safe procedure with improvement of nasal shape, without compromising respiratory function. This technical option represents yet another alternative in the treatment of PMMA granuloma complications. J Drugs Dermatol. 2021;20(11): 1161-1166. doi:10.36849/JDD.6550.

RAG1 splicing mutation causes enhanced B cell differentiation and autoantibody production.

Hypomorphic RAG1 or RAG2 mutations cause primary immunodeficiencies and can lead to autoimmunity, but the underlying mechanisms are elusive. We report here a patient carrying a c.116+2T>G homozygous splice site mutation in the first intron of RAG1, which led to aberrant splicing and greatly reduced RAG1 protein expression. B cell development was blocked at both the pro-B to pre-B transition and the pre-B to immature B cell differentiation step. The patient B cells had reduced B cell receptor repertoire diversity and decreased complementarity determining region 3 lengths. Despite B cell lymphopenia, the patient had abundant plasma cells in the BM and produced large quantities of IgM and IgG Abs, including autoantibodies. The proportion of naive B cells was reduced while the frequency of IgD-CD27- double-negative (DN) B cells, which quickly differentiated into Ab-secreting plasma cells upon stimulation, was greatly increased. Immune phenotype analysis of 52 patients with primary immunodeficiency revealed a strong association of the increased proportion of DN B and memory B cells with decreased number and proportion of naive B cells. These results suggest that the lymphopenic environment triggered naive B cell differentiation into DN B and memory B cells, leading to increased Ab production.

Nódulos palpebrales en el granuloma aséptico facial idiopático / Eyelid nodules in idiopathic facial aseptic granuloma

El granuloma aséptico facial idiopático (GAFI) es una entidad recientemente descrita y poco frecuente. Se considera una forma de rosácea granulomatosa infantil. Es menos frecuente el GAFI con nódulos faciales y palpebrales asociados. Describimos 3casos GAFI que presentan esta asociación. Son niños sanos sin ningún antecedente traumático. El examen de la biopsia realizada en uno de los pacientes reveló granulomas inflamatorios no caseificantes. Se han ensayado distintos tratamientos médicos que parecen acelerar su curación, aunque su tendencia es la resolución espontánea en el plazo de varios meses. Los nódulos palpebrales indoloros de repetición se pueden confundir con el chalazión. Debemos pensar en GAFI ante nódulos palpebrales de larga evolución (AU)

Idiopathic facial aseptic granuloma (IFAG) is a recently described and rare condition. It is considered a form of infantile granulomatous rosacea. IFAG with facial and eyelid nodules is very rare. A description is presented of 3cases of IFAG eyelid nodules. They concern healthy children with no history of trauma. Biopsy examination revealed non-caseating inflammatory granulomas. Different medical treatments have been tried that seem to accelerate its healing, although its tendency is spontaneous resolution within several months. Painless recurrent eyelid nodules can be confused with chalazion. The diagnosis of IFAG should be considered in chronic eyelid nodules (AU)

Concurrent diffuse dermal angiomatosis and granuloma inframammary adultorum of the breast.

Diffuse dermal angiomatosis (DDA) is a cutaneous reactive angiomatosis. Typically presenting as ulcerated, erythematous, violaceous, or purpuric plaques on the breast or lower extremities, DDA is believed to be a reaction to tissue ischemia. Granuloma inframammary adultorum (GIA) is a type of irritant dermatitis of multifactorial etiology, clinically presenting as papules and nodules. Herein, we report an interesting rash presenting as fungiform papulonodules overlying a large violaceous plaque on the left breast. Biopsy revealed an exuberant epidermal proliferation and a diffuse and deep dermal proliferation, consisting of small slit-like blood vessels in between collagen bundles. In light of these clinical and histopathologic findings in the setting of an indurated plaque on a pendulous breast of a woman with multiple risk factors for local tissue ischemia, a diagnosis of concurrent diffuse angiomatosis of the breast (DDAB) and GIA was rendered. This case highlights the critical importance of clinicopathologic correlation in the diagnosis of multiple diagnostic entities.

Interventional therapy via flexible bronchoscopy in the management of foreign body-related occlusive endobronchial granulation tissue formation in children.

BACKGROUND: Occlusive granulation tissue formation, as one of the most common sequelae of chronic foreign body aspiration, can cause tracheobronchial obstruction and delayed fixed airway stenosis necessitating interventions. The aim of this study was to explore the clinical efficacy and safety of interventional therapy via flexible bronchoscopy for treatment of granulation tissue related airway obstruction secondary to foreign body aspiration in children. METHOD: Patients with long-term foreign body related granulation tissue were treated with flexible bronchoscopy therapeutic modalities, including forceps, cryotherapy, holmium laser, and balloon dilatation. Clinical efficacy was evaluated by clinical symptoms and endoscopic manifestations. RESULTS: A total of eight patients with granulation tissue hyperplasia caused by foreign body in bronchus, with a median age of 29.5 (range, 18-54) months, underwent interventional therapy between January 2016 and December 2019. Four patients received forceps and CO2 cryotherapy and one patient required forceps only. The remaining three patients received holmium laser combined with CO2 cryotherapy, and one of them required additional balloon dilatation. Four cases required a second cryotherapy procedure, and one case received three cryotherapy procedures for extensive granulation tissue. The treatment efficacy was 100% without complications. CONCLUSION: Interventional procedure via flexible bronchoscopy is a safe, reliable, and effective method in the management of tracheobronchial obstruction and stenosis caused by foreign body-related granulation tissue hyperplasia. It is worthy of clinical application.

Chronic Granulomatous Invasive Fungal Sinusitis: A Case Series and Literature Review.

Chronic granulomatous invasive fungal sinusitis (CGIFS) is a peculiar disease of the paranasal sinuses due to its rarity, patient subset, and disease course. We describe 7 cases of histopathologically confirmed CGIFS with different treatment plans and varying outcomes. Of particular note was that one of these patients developed allergic fungal rhinosinusitis after complete resolution of his primary invasive disease, a finding that has never been reported in the literature. Another patient had an atypical fungal species (Aspergillus nidulans) on fungal stain and culture, while one immunodeficient patient had a large intracerebral disease component and died after 2 months of treatment. We also present a review of the pertinent literature investigating this rare disease.

Clinical Features and Prognostic Factors in Northern Chinese Patients with Peripheral Granuloma Type of Ocular Toxocariasis: A Retrospective Cohort Study.

PURPOSE: To summarize the clinical features and probable factors associated with recurrence within 6 months in northern Chinese ocular toxocariasis (OT) patients. METHODS: A retrospective cohort study (38 OT eyes) was conducted. Clinical features, aqueous inflammatory cytokines, complications, and parameters associated with recurrence after treatment were analyzed. RESULTS: The initial best-corrected visual acuity (BCVA) was related to the anterior inflammation grade at the onset (P = .028). The mean BCVA and anterior inflammation improved significantly (P < .05) after treatment. The OT eyes had higher aqueous humor cytokine levels (IL-6, IL-8, and IL-10) compared with the normal eyes (P < .001). More severe anterior inflammation grade or longer duration of uveitis were more likely to increase the probability of recurrence (P = .008 and P = .025), TA injection during/after vitreous surgery can reduce the probability of recurrence (P = .031). CONCLUSIONS: The combination therapy of vitreoretinal surgery, steroids, and albendazole therapy may reduce inflammation and recurrence of OT effectively.Abbreviations: BCVA: best-corrected visual acuity; BFGF: basic fibroblast growth factor; CFT: central foveal thickness; CI: confidence interval; ELISA: Enzyme-linked immunosorbent assay; ERM: epiretinal membrane; IOP: intraocular pressure; IQR: interquartile range; IL: interleukin; LFM: laser flare meter; MH: macular hole; OCT: optical coherence tomography; OR: odds ratio; OT: ocular toxocariasis; RD: retinal detachment; TA: triamcinolone acetonide; TCLA: Toxocara canis larva crude antigen; TGF: transforming growth factor; VCAM: vascular cell adhesion molecule; VEGF: vascular endothelial growth factor.

Rubella virus-associated chronic inflammation in primary immunodeficiency diseases.

PURPOSE OF THE REVIEW: The aim of this article is to summarize recent data on rubella virus (RuV) vaccine in chronic inflammation focusing on granulomas in individuals with primary immunodeficiencies (PIDs). RECENT FINDINGS: The live attenuated RuV vaccine has been recently associated with cutaneous and visceral granulomas in children with various PIDs. RuV vaccine strain can persist for decades subclinically in currently unknown body site(s) before emerging in granulomas. Histologically, RuV is predominately localized in M2 macrophages in the granuloma centers. Multiple mutations accumulate during persistence resulting in emergence of immunodeficiency-related vaccine-derived rubella viruses (iVDRVs) with altered immunological, replication, and persistence properties. Viral RNA was detected in granuloma biopsies and nasopharyngeal secretions and infectious virus were isolated from the granuloma lesions. The risk of iVDRV transmissibility to contacts needs to be evaluated. Several broad-spectrum antiviral drugs have been tested recently but did not provide significant clinical improvement. Hematopoietic stem cell transplantation remains the only reliable option for curing chronic RuV-associated granulomas in PIDs. SUMMARY: Persistence of vaccine-derived RuVs appears to be a crucial factor in a significant proportion of granulomatous disease in PIDs. RuV testing of granulomas in PID individuals might help with case management.

Granulomas and nongranulomatous nodules after filler injection: Different complications require different treatments.

Dermal fillers are widely used for facial rejuvenation and reconstruction and present fewer risks than surgical approaches. Nevertheless, several complications may occur, including nodule formation. A nodule is a clinical sign corresponding to different etiologies, such as overcorrection, infection, allergic reaction, or granuloma. However, their treatment represents a diagnostic challenge. We present a retrospective review of 26 consecutive patients who underwent a biopsy for facial nodule formation more than 3 months after filler injections, to determine the diagnosis of the nodule and type of filler used. All patients were women (mean age, 57.8 years). Some patients suffered from different localizations: lip, 14 cases; nasolabial folds, 6; cheeks, 5; infraorbital region, 5; the glabella, 2; the temporal region, 1; and chin, 1 case. Only 5 (19.2%) patients knew the type of filler used, and in another 4 cases, the injector was able to provide some information. In 65.4% of cases, the filler type was unknown. Histopathological analysis revealed a "granulomatous" nodule in 30 sites and a "non-granulomatous" nodule in 4 cases. Concerning the type of filler, 5 different histopathological patterns were found. Our results demonstrate that a clinical history and histopathological analysis whether to confirm or not to confirm the diagnosis of granuloma and to identify the type of filler are essential tools to achieve an accurate diagnosis of the problem-oriented treatment of nodules after dermal filler injections. We propose an algorithm for the management of nodules after filler injection.