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ABSTRACT Background Methods Results Conclusion There is a known association between common variable immunodeficiency (CVID) and granulomas in multiple organ systems, including the skin, lung, liver, and spleen. Rubella virus has also been detected within cutaneous granulomas in both immunocompetent and immunocompromised hosts. We present a retrospective case series of patients with CVID and granulomatous skin disease and describe the spectrum of clinical and histopathologic features, including the status of rubella virus in the cutaneous granulomas.We retrospectively reviewed the clinical and histopathological characteristics of patients diagnosed with CVID at our institution, with cutaneous findings and skin biopsies available for review between 1990 and 2023, demonstrating granulomatous inflammation.Eight patients met the inclusion criteria. The most common histopathologic pattern was palisaded granulomatous inflammation, seen in five of eight cases. Three cases showed strictly sarcoidal granulomas. Background inflammation was peri‐granulomatous (8/8) and the predominant background inflammatory cell type was lymphocytic (6/8). Rubella virus testing was performed for seven of eight cases and found to be positive in one case.Cutaneous granulomatous disease in CVID can present with a spectrum of clinical morphologies, granulomatous patterns, and variable rubella virus persistence. Dermatopathologists should be aware of the spectrum of findings when considering cutaneous CVID–related granulomatous disease in the differential diagnosis. [ABSTRACT FROM AUTHOR]

A strong association between rubella virus (RuV) and chronic granulomas, in individuals with inborn errors of immunity, has been recently established. Both the RA27/3 vaccine and wild-type RuV strains were highly sensitive to a broad-spectrum antiviral drug, nitazoxanide (NTZ), in vitro. However, NTZ treatment, used as a salvage therapy, resulted in little or no improvements of RuV-associated cutaneous granulomas in patients. Here, we report investigations of possible causes of treatment failures in two ataxia-telangiectasia patients. Although a reduction in RuV RNA in skin lesions was detected by real-time RT-PCR, live immunodeficiency-related vaccine-derived rubella viruses (iVDRV) were recovered from granulomas, before and after the treatments. Tizoxanide, an active NTZ metabolite, inhibited replications of all iVDRVs in cultured A549 cells, but the 50% and 90% inhibitory concentrations were 10-40 times higher than those for the RA27/3 strain. There were no substantial differences in iVDRV sensitivities, neither before nor after treatments. Analysis of quasispecies in the E1 gene, a suspected NTZ target, showed no effect of NTZ treatments on quasispecies' complexity in lesions. Thus, failures of NTZ therapies were likely due to low sensitivities of iVDRVs to the drug, and not related to the emergence of resistance, following long-term NTZ treatments.

A strong association between rubella virus (RuV) and chronic granulomas, in individuals with inborn errors of immunity, has been recently established. Both the RA27/3 vaccine and wild-type RuV strains were highly sensitive to a broad-spectrum antiviral drug, nitazoxanide (NTZ), in vitro. However, NTZ treatment, used as a salvage therapy, resulted in little or no improvements of RuV-associated cutaneous granulomas in patients. Here, we report investigations of possible causes of treatment failures in two ataxia-telangiectasia patients. Although a reduction in RuV RNA in skin lesions was detected by real-time RT-PCR, live immunodeficiency-related vaccine-derived rubella viruses (iVDRV) were recovered from granulomas, before and after the treatments. Tizoxanide, an active NTZ metabolite, inhibited replications of all iVDRVs in cultured A549 cells, but the 50% and 90% inhibitory concentrations were 10–40 times higher than those for the RA27/3 strain. There were no substantial differences in iVDRV sensitivities, neither before nor after treatments. Analysis of quasispecies in the E1 gene, a suspected NTZ target, showed no effect of NTZ treatments on quasispecies’ complexity in lesions. Thus, failures of NTZ therapies were likely due to low sensitivities of iVDRVs to the drug, and not related to the emergence of resistance, following long-term NTZ treatments.

Abstract Background Schizophyllum commune, a basidiomycetous fungus, is a common invader of rotten wood. This fungus rarely causes mycotic disease in humans, especially cutaneous infection. In this paper, we describe the first case of cutaneous granuloma caused by S. commune in a Chinese woman. Case presentation A 25-year-old female with a two-year history of erythema, papules, nodules, and scales on her sole of left foot was presented to our outpatient center. Samples were obtained by the scraping of lesion and for light microscopy. Hyphae were observed by microscopic examination. We carried out a skin tissue biopsy, which showed multiple granulomatous nodules. Biopsy specimens were also inoculated onto media. After being cultured on SDA at 27 °C for 7 days, spreading-woolly-white colonies grew on the inoculation sites of media containing chloramphenicol only and there,s no other colonies grew. S. commune was identified by morphology methods, biochemical tests, and PCR sequencing. Pathological findings also aided in diagnosing cutaneous fungal granuloma. Oral itraconazole was applied. After 1 month of therapy, rashes on her left foot and pain were improved. Conclusion We describe the first case of cutaneous granuloma caused by Schizophyllum commune, which illustrates the importance of recognizing uncommon pathogenic fungal infections.

Ataxia-telangiectasia (AT) is an autosomal recessive disorder due to defective DNA damage repair. It is characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias and immune system dysregulation resulting in recurrent and progressive sino-pulmonary infections. We present a case of a 4 year old male child with delayed motor development and recurrent sino-pulmonary infections and complaints of multiple asymptomatic plaques over knees and nodules over elbows since 3 years. On investigations and genetic testing he was diagnosed as a case of AT. Biopsy of the lesion over knees showed non- infectious granulomas. We report the case owing to rarity of association of non-infectious cutaneous granuloma with AT. [ABSTRACT FROM AUTHOR]

Cutaneous granulomas in dolphins were believed to be caused by Lacazia loboi, which also causes a similar disease in humans. This hypothesis was recently challenged by reports that fungal DNA sequences from dolphins grouped this pathogen with Paracoccidioides brasiliensis. We conducted phylogenetic analysis of fungi from 6 bottlenose dolphins (Tursiops truncatus) with cutaneous granulomas and chains of yeast cells in infected tissues. Kex gene sequences of P. brasiliensis from dolphins showed 100% homology with sequences from cultivated P. brasiliensis, 73% with those of L. loboi, and 93% with those of P. lutzii. Parsimony analysis placed DNA sequences from dolphins within a cluster with human P. brasiliensis strains. This cluster was the sister taxon to P. lutzii and L. loboi. Our molecular data support previous findings and suggest that a novel uncultivated strain of P. brasiliensis restricted to cutaneous lesions in dolphins is probably the cause of lacaziosis/lobomycosis, herein referred to as paracoccidioidomycosis ceti.

Background: Histopathologic diagnosis of borderline tuberculoid leprosy (BTL) is fraught with hurdles. It overlaps with other granulomas and documenting nerve involvement is the key to correct diagnosis. This is difficult on H and E sections alone. S-100 immunostaining may help in this regard. Objectives: To study the patterns of nerve involvement in BTL and other cutaneous granulomas using S-100 immunostain and compare its sensitivity with that of H and E staining, in both adequate and inadequate biopsies. Materials and Methods: A total of 20 cases of BTL were reviewed. And, 19 biopsies from other cutaneous granulomas were taken as controls. S-100 immunostaining was done on paraffin sections. The pattern of nerve involvement was graded as intact, infiltrated and/or fragmented, intact with perineural inflammation. Results: Of the 20 cases of BTL, S-100 demonstrated infiltrated and/or fragmented nerves in 15 and absent nerves in 5 cases. H and E stain identified neuritis in eight cases. The sensitivity of S-100 and H and E is 0.78 and 0.41. In the 19 controls, S-100 identified normal nerves in 16 with 7 showing perineural inflammation only and their absence in 2 cases. H and E identified normal nerves in nine cases. The sensitivity of S-100 and H and E is 0.83 and 0.41. In biopsies where subcutis was absent, the sensitivity of S-100 in identifying nerve involvement is 0.66 compared with H and E 0.33. Conclusion: S-100 staining is an efficient ancillary aid in distinguishing BTL from other granulomas and is superior to H and E in identifying nerve involvement, even where subcutis is absent. Infiltration and/or fragmentation of nerves by S-100 is the only reliable marker of BTL. [ABSTRACT FROM AUTHOR]

Abstract: Cutaneous infections can present with a great variety of histological findings. Granulomatous infiltrates represent a reaction pattern commonly seen in this setting. However, it cannot be forgotten that granulomatous infiltrates do not equate an infective process. In the present article, we present a review of current concepts regarding the definition, pathogenesis, classification and diagnosis of cutaneous granulomatous infiltrates. The main types of granulomas associated with infectious processes are reviewed, including suppurative, tuberculoid and the so-called “histiocytic granulomas” (diffuse infiltrates composed of histiocytes frequently containing intracellular organisms). The most representative infections in immunocompetent patients associated with each group are discussed. In suppurative granulomas, the discussion includes deep fungal infections and atypical mycobacterioses. In tuberculoid granulomas, the main entities discussed include tuberculosis, tuberculoid leprosy and syphilis. With respect to histiocytic granulomas, emphasis will be put on cutaneous leishmaniasis, with a brief mention of other entities. The main non-infectious entities included in the differential diagnosis of each of these granulomatous infiltrates will also be discussed. [Copyright &y& Elsevier]

Background: Non-infective cutaneous granulomas with unknown pathogenesis occur in various primary immunodeficiencies (PIDs) including ataxia telangiectasia (A-T). Objective: To find a common immunological denominator in these cutaneous granulomas. Methods: The dermatological and immunological features of 4 patients with A-T and cutaneous granulomas were described. The literature on skin granulomas in A-T and in other PIDs is reviewed. Results: All 4 A-T patients had progressive granulomas on their limbs and showed decreased IgG and IgA concentrations with normal IgM levels. They had a marked decrease in B cells and naïve T cells coinciding with the appearance of the cutaneous granulomas. Similar B- and T-cell abnormalities were described in patients with other PIDs with skin granulomas. Conclusions: We hypothesize that the pathogenesis of these skin granulomas is related to immune dysregulation of macrophages due to the absence of naïve T cells with an appropriate T-cell receptor repertoire and the unopposed activity of γδ T cells and/or natural killer cells. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cutaneous granulomas are uncommon in primary immunodeficiency disorders. We report cutaneous granulomas in a child with ataxia telangiectasia (AT) and compare the clinical course with similar lesions in an adult with common variable immunodeficiency (CVI). A 4-year-old female with AT developed cutaneous granulomas as erythematous plaques. The largest lesion appeared on her left cheek and continued to progress despite treatment with topical and intralesional steroids. Disease control was obtained initially with oral antibiotics and low-dose oral steroids. On cessation of oral steroids, significant relapse of the facial granuloma occurred. Pulsed and then oral steroids were required to stop the disease process leaving significant scarring. The second case is of cutaneous granulomas in a 66-year-old man, with CVI, who presented with an erythematous reticulate rash on the legs. We consider it useful to report this patient here as disease control was obtained in a similar way with systemic immunosuppression. In this patient a combination of oral steroids and azathioprine was used. These cutaneous granulomas are thought to be a manifestation of immune dysregulation. No infectious cause has been found so far. We recommend the use of broad-spectrum antibiotics in conjunction with systemic steroids for progressive granulomas, as these patients are immunosuppressed and infection with an unidentified organism cannot be excluded. [ABSTRACT FROM AUTHOR]

Development of cutaneous granulomas in 8 patients with ataxia-telangiectasia is reported from the Departments of Pediatrics and Dermatology, Northwestern University Medical School, Chicago, IL; the Hospital for Sick Children, Toronto, Canada; Henry Ford Hospital, Detroit, MI; and University of North Carolina, Chapel Hill.

Background: Schizophyllum commune, a basidiomycetous fungus, is a common invader of rotten wood. This fungus rarely causes mycotic disease in humans, especially cutaneous infection. In this paper, we describe the first case of cutaneous granuloma caused by S. commune in a Chinese woman.Case Presentation: A 25-year-old female with a two-year history of erythema, papules, nodules, and scales on her sole of left foot was presented to our outpatient center. Samples were obtained by the scraping of lesion and for light microscopy. Hyphae were observed by microscopic examination. We carried out a skin tissue biopsy, which showed multiple granulomatous nodules. Biopsy specimens were also inoculated onto media. After being cultured on SDA at 27 °C for 7 days, spreading-woolly-white colonies grew on the inoculation sites of media containing chloramphenicol only and there,s no other colonies grew. S. commune was identified by morphology methods, biochemical tests, and PCR sequencing. Pathological findings also aided in diagnosing cutaneous fungal granuloma. Oral itraconazole was applied. After 1 month of therapy, rashes on her left foot and pain were improved.Conclusion: We describe the first case of cutaneous granuloma caused by Schizophyllum commune, which illustrates the importance of recognizing uncommon pathogenic fungal infections. [ABSTRACT FROM AUTHOR]