Cutaneous Granulomas Research Articles

Interstitial granulomatous dermatitis: a characteristic histological pattern with variable clinical manifestations.

Interstitial granulomatous dermatitis (IGD) is a distinct histopathological pattern with a diverse clinical appearance which can be associated with autoimmune systemic diseases or, rarely, with drug-related adverse reactions. The IGD is a rare entity, first described in 1993 by Ackerman, which belongs to a group of non-infectious cutaneous granulomas [1]. The disease affects mostly women, at the mean age of onset at 58 years [2]. The precise etiopathogenesis remains unknown, but the underlying inflammatory process of the dermis and granulomatous infiltrate can be involved in the development of the disease. One hypothesis suggests that the depositions of immune complexes in the dermal vessels may be the trigger, which is then followed by complement and neutrophil activation and damage of dermal collagen, which in response gives rise to a granulomatous infiltrate [3]. We present a case of IGD that seems to be a distinct entity with variable clinical manifestations, which can be easily differentiated from other granulomatous skin diseases on the basis of histopathological examination. Although the disease occurs more frequently in adults, we present a case of IGD in a child.

Live rubella virus vaccine long-term persistence as an antigenic trigger of cutaneous granulomas in patients with primary immunodeficiency

Granulomas may develop as a response to a local antigenic trigger, leading to the activation of macrophages and T-lymphocytes. Primary immunodeficiency (PID) is associated with the development of extensive cutaneous granulomas, whose aetiology remains unknown. We performed high-throughput sequencing of the transcriptome of cutaneous granuloma lesions on two consecutive index cases, and RT-PCR in a third consecutive patient. The RA27/3 vaccine strain of rubella virus—the core component of a universally used paediatric vaccine—was present in the cutaneous granuloma of these three consecutive PID patients. Controls included the healthy skin of two patients, non-granulomatous cutaneous lesions of patients with immunodeficiency, and skin biopsy samples of healthy individuals, and were negative. Expression of viral antigens was confirmed by immunofluorescence. Persistence of the rubella vaccine virus was also demonstrated in granuloma lesions sampled 4-5 years earlier. The persistence of the rubella virus vaccine strain in all three consecutive cutaneous granuloma patients with PID strongly suggests a causal relationship between rubella virus and granuloma in this setting.

Development of a microplate-reverse hybridization method for the detection and identification of common pathogens in lesions of cutaneous infectious granuloma

Objective To develop a microplate-reverse hybridization method combined with PCR-enzymelinked immunosorbent assay (simulant chip) for the detection and identification of common species of mycobacteria and fungi in lesions of cutaneous infectious granuloma.Methods Two universal primers for mycobacteria and fungi,as well as specific probes for 10 common pathogens of cutaneous infectious granuloma (including Mycobacterium tuberculosis,Mycobacterium leprae,Mycobacterium marinum,Mycobacterium abscessus,Mycobacterium fortuitum,Sporotrichum schencki,Cladosporium carrionii,Fonseceea pedrosoi,Fonseceea monophora and Candida albicans),were designed.To test the performance of the universe primers,PCR was performed with them to amplify corresponding fragments from the standard strains of the 10 pathogens followed by sequencing.A simulant chip method was developed with the specific probes,and used to detect 10 standard and 19 clinical strains of these pathogens in simulated tissue specimens.The sensitivity and specificity of this method were determined.Results The corresponding fragments were amplified from all the standard strains by PCR with the two pairs of universal primers,and these PCR products were confirmed to match with the expected genes.As the simulant chip method showed,the absorbance value was 0.041 ± 0.02 for negative specimens,and the cut-off point was determined as 0.101 for this method.At this cut-off point,the detection limit of the simulant chip method was 1 × 101 to 1 × 102 cells/ml for these pathogens.No cross reaction was observed for these specific probes between these 10 pathogens.The genotyping results for these clinical isolates were consistent between the simulant chip method and DNA sequencing.Conclusion The established simulant chip method is a rapid method for the detection and identification of common pathogens from cutaneous infectious granuloma. Key words: Granuloma; Mycobacterium infections; Fungal infections; Oligonucleotide reverse hybridization techniques

E-Cadherin Is Expressed by Mono- and Multinucleated Histiocytes in Cutaneous Sarcoidal and Foreign Body Granulomas

E-cadherin, a member of the cadherin family of transmembrane adhesion receptors, is critical for cutaneous barrier function, as it promotes keratinocyte and Langerhans cell adhesion in the epidermis. Recent murine models of chronic inflammation identified new E-cadherin expressing subsets of mononuclear phagocytes, including alternatively activated macrophages and selected inflammatory dendritic cells. It has been shown in vitro that expression of E-cadherin by murine macrophages promotes their homotypic aggregation and fusion to multinucleated giant cells (MNGCs), a signature cell type of granulomatous inflammation. The purpose of this study was to assess E-cadherin expression on histiocytes and giant cells in cutaneous granulomas in humans. E-cadherin expression was evaluated by immunohistochemistry of formalin-fixed paraffin-embedded skin biopsies of foreign body granulomas (n = 21) and sarcoidosis (n = 21). The results showed consistent membranous E-cadherin staining pattern on mononucleated histiocytes and MNGCs in both granuloma types. These E-cadherin expressing histiocytes are distinct from dermal Langerhans cells because they lacked CD1a expression. Our findings suggest that E-cadherin expressing mononuclear histiocytes are likely precursors for MNGCs in cutaneous granulomas and may play a critical role in disease pathogenesis.

Infliximab for treatment of granulomatous disease in patients with common variable immunodeficiency.

Eight to 22 % of common variable immunodeficiency (CVID) patients exhibit granulomas of the lungs, spleen, liver, and/or skin. Granulomas can be the most medically significant day-to-day problem for CVID patients. Currently, there are limited options for treatment of granulomas associated with CVID. We treated five patients with CVID who exhibited significant clinical symptoms secondary to granulomas with infliximab. The patients were selected and treated based solely on clinical need and were not otherwise controlled or blinded to the therapy. After obtaining baseline studies (labs, spirometry, radiology) and excluding infection, they were treated with infliximab 5 mg/kg at week 0, 2, 6 and every 4 weeks thereafter. Post treatment improvements were seen in all 5 patients with significant clinical responses observed for both visceral and cutaneous granulomata. Four of the five patients were maintained on infliximab for 5 to 18 months (mean 9.4 months) without adverse reaction or increased susceptibility to infection. One patient completed 6 months of therapy with improvement of respiratory parameters but discontinued infliximab due to joint stiffness and rash that she attributed to the medication. In our series, infliximab (5 mg/kg monthly) was an effective treatment for cutaneous and visceral granulomas in patients with CVID.

Isolation of dematiaceous fungi from soil of Mashhad, Neyshabur(north-east) and Isfahan(center of Iran) cities

Dematiaceous fungi can infect patients who are immunocompetent and as well as may be related to in a wide variety of disorders.This study aimed to isolate and identify dematiaceous fungi from soil of Mashhad, Neyshabur and Isfahan cities.Of 93 strains isolated, the frequency of Ulocladium , Cladosporium , Aureobasidium and Alternaria were as 38.7%, 30.2%, 10.7% and 6.4%, respectively by microscopic examination. Also 13.9% were sterile hyphae. In this study, ulocladiumsp were the predominant fungi among all of the dematiaceous fungi. Although ulocladiumsp that formerly was identified as non-pathogenic saprophyte, have recently been reported in various diseases such as asthma, allergic rhinitis, hypersensitivity pneumonitis, chronic wounds, onychomycosis, cutaneous granulomas and keratitis

Expression of Notch Signaling Components in Cutaneous Foreign Body and Sarcoidal Granulomas and Fusing Macrophages

The evolutionarily conserved Notch signaling pathway affects tissue-specific cell differentiation, proliferation, and apoptosis. In the immune system, Notch has been implicated in the development and function of both adoptive and innate immune cells. Notch signaling is initiated by Notch receptor binding to cognate ligands, which results in the enzymatic cleavage and intranuclear translocation of the intracellular domain of Notch receptor (ICN). Recent murine models of chronic inflammation highlighted a critical role for a Notch ligand, Delta-like ligand (Dll)-4, in granuloma formation. In this study, we aimed to assess Notch-1 receptor activation and Dll4 expression in human cutaneous granulomas and in cultured human macrophages and multinucleated giant cells. ICN1 and Dll4 expression was evaluated by immunohistochemistry of cutaneous foreign body (n = 15) and sarcoidal (n = 19) granulomas. The results showed consistent intranuclear staining for ICN1 in foreign body but not in sarcoidal granulomas and strong cytoplasmic staining for Dll4 in mononuclear histiocytes and multinucleate giant cells in both types of granulomas. Additionally, immunofluorescence confocal microscopy showed ICN1 and Dll4 expression by cultured human macrophages undergoing fusion in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. These findings indicate a potential role for the Notch-1-Dll4 signaling pathway in foreign body-induced granulomatous reactions and possibly distinct Notch pathway utilization in sarcoidal granulomas.

Expression of IFN‐γ, IL‐4, and IL‐17 in cutaneous schistosomal granuloma

Cutaneous schistosomal granuloma (CSG) is a rare dermatological disease, the clinical and histopathological features of which are well defined. Although a panoramic picture of its immunopathogenesis in humans is not yet available, it is believed to be induced by T helper1 (Th1), Th2, or Th17 cytokines in animals. This study evaluated the expression of different types of Th cytokines, including Th1 cytokine interferon-γ (IFN-γ), Th2 cytokine interleukin-4 (IL-4), and Th17 cytokine IL-17, in human CSG. This study included nine patients with CSG. Dermatological examinations were conducted in all subjects. Skin biopsy specimens were stained with hematoxylin and eosin (H&E). Immunohistochemical examination was performed using three monoclonal anti-human antibodies against IFN-γ, IL-4, and IL-17 to evaluate Th1, Th2, and Th17 cytokines, respectively. The most common site of CSG manifestation was the paraumbilical area, which was affected in 66.7% of patients. All lesional skin biopsy specimens revealed multiple dermal granulomas surrounding schistosomal eggs. Positive immunoreactivity for IFN-γ, IL-4, and IL-17 was present in dermal inflammatory infiltrate in 88.9, 11.1, and 88.9% of subjects, respectively. There were statistically significant negative correlations between the duration of disease and both IFN-γ and IL-17 (P≤0.05), and a statistically significant positive correlation between IFN-γ and IL-17 (P≤0.05). This study suggests that CSG is formed by the action of both Th1 (IFN-γ) and Th17 (IL-17) cytokines, which have been shown to be directed against the schistosomal egg to induce a cell-mediated immune response.

Cutaneous Granulomas and Epidermodysplasia Verruciformis in Early Onset Combined Immunodeficiency Syndrome

Cutaneous granulomas with prominent caseating necrosis are a rare manifestation of immunodeficiency. Extensive and recalcitrant cutaneous viral infections can also be seen. We present a case of an 18-year-old white man with an early onset poorly characterized combined immunodeficiency syndrome who, over the past 5 years, developed enlarging tender red-purple plaques on his extremities and pink near-confluent macules on his chest and back. Previous biopsies of the red-purple plaques showed features of granuloma annulare. Histopathological examination of old and new biopsies revealed both sarcoidal and palisading necrobiotic granulomas with perforating features and elastophagocytosis. Stains and tissue cultures were negative for bacterial and fungal organisms. In addition, biopsy of a macule on the back demonstrated verruca plana with characteristics of epidermodysplasia verruciformis. As an infant, the patient had failure to thrive and a combined immunodeficiency, but was lost to follow-up for 15 years. He currently continues to have severe hypogammaglobinemia and cellular immunodeficiency. Intravenous immunoglobulin and prednisone were initiated and his plaques improved rapidly. Topical imiquimod was ineffective for the verruca plana. The patient and his parents are currently undergoing whole exome sequencing including evaluation for epidermodysplasia verruciformis 1 and 2 gene mutations. This case highlights the importance of including genetic immunodeficiency disorders in the clinical and histopathological differential diagnosis for cutaneous sarcoidal or palisading necrobiotic granulomas and for extensive cutaneous viral infection.

S-100 immunostaining in the Distinction of Borderline Tuberculoid Leprosy from other Cutaneous Granulomas.

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.

Sea urchin spine arthritis of the proximal interphalangeal joint of the hand: radiological, intraoperative and histopathological findings.

Penetrating sea urchin spine injuries, can lead to devastating, irreversible consequences. Persistent inflammation, cutaneous granuloma, neuroma, tenosynovitis, arthritis and destructive arthritis, leading to permanent loss of function and digit amputation, can occur. We present a case of a patient who developed sea urchin spine arthritis of the proximal interphalangeal joint. Only 17 cases of sea urchin spine arthritis of the hand have been documented in the medical literature. However, in this case, the article also includes sequential radiographs, histopathological slides, and intra-operative photographs.

Bacillus Calmette-Gu�rin (BCG) Vaccine-Induced Disease in Healthy Infants: Identification of BCG Gene from Formalin-Fixed Paraffin-Embedded Tissue

Background: Bacillus Calmette-Guérin (BCG) vaccineinduced systemic complication is rare but localized skin lesion develops in the site of inoculation in healthy infants. Methods: In this report, we described three cases of BCG vaccineinduced skin lesions in healthy immunocompetent infants and a method of identification of BCG gene by polymerase chain reaction (PCR) form fresh frozen of formalin-fixed and paraffinembedded tissue samples. Results: These cases had a history of BCG vaccination but no family history of tuberculosis and no contact with patients of tuberculosis. Two cases developed cutaneous granuloma in the axilla of ipsilateral side of BCG inoculation. Another case showed granulomatous osteomyelitis of the left 6th rib. Histological examination demonstrated typical pathologic findings for epithelioid granuloma with caseation necrosis, indicating mycobacterium infection. PCR analysis from fresh frozen or formalin-fixed paraffin-embedded tissue rapidly confirmed the infection of Mycobacterium bovis BCG but not M. tuberculosis. Conclusion: BCG infection should be considered even in healthy infants with a history of BCG vaccination and histology of epithelioid granuloma with caseation necrosis. In such cases, BCG gene identification by PCR would be useful even from formalin-fixed and paraffin embedded tissue samples.

Treatment of Pediatric Pyogenic Granulomas Using β‐Adrenergic Receptor Antagonists

Propranolol and timolol are nonselective ß-adrenergic antagonists that induce peripheral vasoconstriction and affect angiogenic cytokines. Oral and topical ß-blocker therapy has become the de facto first-line treatment for complicated infantile hemangiomas because of its superior efficacy and tolerability. Pyogenic granulomas or lobular capillary hemangiomas are common acquired vascular tumors accounting for 0.5% of all skin nodules in children. Although they are benign vascular proliferations, treatment is often sought because of recurrent episodes of bleeding and for cosmetic considerations. Numerous treatment options are available, but recurrence rates are high. Noninvasive methods of treatment are being sought, particularly for young children. Herein we report a series of seven cases of cutaneous and mucosal pyogenic granulomas treated successfully using oral or topical ß-blockers.

Skin Manifestations of Primary Immune Deficiency

Cutaneous manifestations are common in primary immune deficiency diseases, affecting between 40 % and 70 % of patients with diagnosed primary immune deficiency. Skin infections characterize many primary immune deficiencies, but there are also frequent noninfectious cutaneous manifestations seen in many of these disorders, including eczematous lesions, erythroderma, cutaneous granulomas, dysplasia of skin, hair, and nails, autoimmune conditions, and frank vasculitis. For the patient with suspected primary immunodeficiency, much can be inferred by evaluating the presenting cutaneous findings, including various infectious susceptibilities, presence of atopy, and evidence of impaired or overactive inflammatory response. The skin manifestations of primary immune deficiency diseases are often early or heralding findings of the underlying immunologic disease. Therefore, awareness of associations between skin findings and immune deficiency may aide in the early detection and treatment of serious or life-threatening immunologic defects. This review summarizes the common skin manifestations of primary immune deficiency diseases and provides the reader with a differential diagnosis of primary immune defects to consider for the most common skin manifestations.

Efectividad del etanol absoluto intralesional en pacientes adultos con granuloma piogénico cutáneo recidivante

Pyogenic granuloma is a reactive vascular hyperplasia. The treatment of choice for de novo lesions is shaving or curettage with electrocoagulation of the base. For recurrent lesions the preferred treatment is surgical excision. Ideally, all treatment modalities should allow histopathologic confirmation of the diagnosis.The percentage of recurrence varies from 0 to 43.5%. The therapeutic arsenal for recurrent lesions is wide and includes sclerosing agents. Absolute ethanol was proposed in 2004 for the treatment of this entity. ObjectiveTo evaluate the effectiveness of absolute ethanol in the treatment of recurrent cutaneous pyogenic granuloma in adult patients. Material and methodsAll patients aged 18 years old or older with a diagnosis of recurrent cutaneous pyogenic granuloma between October 2010 and July 2011 were included.All patients were treated with intralesional injection of absolute ethanol and were evaluated weekly until disappearance of the lesion. Any patients not cured by the fifth week of absolute ethanol application were scheduled to be treated by surgical excision. ResultsThe median age was 35 years; there were four men and three women. The predominant topography was the right upper extremity. All patients reported pain during the application, intensity being 8 out of 10 on a subjective scale. All showed mild edema immediately after treatment. There were no adverse events. All lesions were resolved in a median of 21 days. One patient showed no scar, one had an atrophic post-treatment scar and the remaining patients had eutrophic scars. There were no recurrences 3 months after treatment. ConclusionAbsolute ethanol was effective in the patients treated and constitutes a therapeutic option for recurrent cutaneous pyogenic granulomas in adults.

Ulcerated and nonulcerated nontuberculous cutaneous mycobacterial granulomas in cats and dogs

Mycobacterial granulomas of the skin and subcutis can be caused by one of a number of pathogens. This review concentrates on noncultivable species that cause diseases characterized by focal granuloma(s), namely leproid granuloma (in dogs) and feline leprosy (in cats). Clinically indistinguishable lesions can be caused by tuberculous organisms (Mycobacterium bovis and Mycobacterium microti) and members of the Mycobacterium avium complex. Rapidly growing mycobacterial species that cause infection of the subcutaneous panniculus associated with draining tracts are not discussed. Disease caused by Mycobacterium ulcerans is an important emerging differential diagnosis for ulcerated cutaneous nodules in certain localized regions. CLINICAL LESIONS: Lesions comprise one or multiple nodules in the skin/subcutis. These are generally firm and well circumscribed, and typically become denuded of hair. They may or may not ulcerate, depending on the virulence of the causal organisms and the immune response of the host. The most inexpensive, noninvasive means of diagnosis is by submission of methanol-fixed, Romanowsky-stained smears to a Mycobacterium Reference Laboratory after detecting negatively stained or acid-fast bacilli on cytological smears. Scrapings of material from slides usually provide sufficient mycobacterial DNA to enable identification of the causal organism using sequence analysis of amplicons after PCR using specific mycobacterial primers. Therapy relies upon a combination of marginal resection of easily accessible lesions and treatment using two or three drugs effective against slowly growing mycobacteria, choosing amongst rifampicin, clarithromycin, clofazimine and pradofloxacin/moxifloxacin.

Botryomycome lingual néonatal (à propos d’une observation)

The botryomycoma is a benign tumor that develops as a response to a local trauma. Generally, it occurs in the fingers, the face and the oral cavity. It is often easily recognized. However, the diagnosis between this tumor and other oral tumors, whether benign or malignant, may be difficult in some cases. We report a particular case of a botryomycoma that occurred with no history of a trauma at an earlier age in the tongue, which is an unusual site for this tumor. A 7-month-old infant presented with a polypoid and sessile swelling on the dorsal side of the tongue. This tumor gradually increased in size since birth. Clinically, the appearance of this mass with the gathered vessels inside was similar to that of a benign vascular tumor. A possibly malignant nature was not excluded. A complete resection under general anesthesia was performed. The histologic examination confirmed the diagnosis of pyogenic granuloma. Pyogenic granuloma is a rare benign tumor which is most likely to occur between the age of 11 and 40. The most frequent location encountered for oral cavity is the gingiva. The tongue is rarely a site for its occurrence. Cutaneous pyogenic granuloma may have different aspect from mucosal type and thus may make the diagnosis difficult. Treatment consists on surgical excision and removal of etiological factors that may be source of recurrence.

Cutaneous mercury granuloma

Cutaneous mercury granuloma is rarely encountered. Clinically it may pose difficulty in diagnosis. Here, we report a 23-year-old male presented with erythematous, nodular lesions over the forearm and anterior aspect of chest wall. Metallic mercury in tissue sections appear as dark black, opaque, spherical globules of varying size and number. They are surrounded by granulomatous foreign-body reaction. It is composed of foreign body giant cells and mixed inflammatory infiltrate composed of histiocytes, lymphocytes, plasma cells, and few eosinophils.

A case of disseminated cutaneous granuloma caused by Trichophyton rubrum

A case of disseminated cutaneous granuloma due to Trichophyton rubrum is reported.A 35-year-old man presented with generalized pruritic erythema,plaques and nodules for 8 years.Dermatological examination revealed patchy papules,erythema,infiltrated plaques and nodules on the scalp,face,trunk and limbs,and some of the lesions were slightly scaling and crusting with clear borders and atrophic scar.Also,his bilateral eyelids were swollen,right auricle was impaired,left auricle was deformed,hair,eyebrows and eyelashes were lost,and nails of the fingers and toes were thickened,impaired and even broken.Direct microscopic examination of scrapings from skin lesions showed the presence of branched and septate hyphae,and fungal culture grew Trichophyton rubrum.Skin biopsy specimen revealed epidermal hyperplasia,stratum spinosum hyperplasia and thickening,epithelioid granuloma in the superficial and mid dermis consisting mainly of lymphocytes and plasmocytes with scattered eosinophils and multinucleated giant cells.Periodic acid-Schiff(PAS)and silver stain both showed branched and septate hyphae within the upper dermis.A diagnosis of disseminated cutaneous granuloma caused by Trichophyton rubrum was made.After 3 months of treatment with itraconazole,the lesions subsided with hyperpigmentation and atrophic scar left,and both microscopic examination and fungal culture turned negative.No side effects were observed during the treatment. Key words: Trichophyton; Granuloma; Itraconazole; Dermatomycoses

Detection and characterization ofHistoplasma capsulatumin a German badger (Meles meles) by ITS sequencing and multilocus sequencing analysis

A wild badger (Meles meles) with a severe nodular dermatitis was presented for post mortem examination. Numerous cutaneous granulomas with superficial ulceration were present especially on head, dorsum, and forearms were found at necropsy. Histopathological examination of the skin revealed a severe granulomatous dermatitis with abundant intralesional round to spherical yeast-like cells, 2-5 μm in diameter, altogether consistent with the clinical appearance of histoplasmosis farciminosi. The structures stained positively with Grocott's methenamine silver and Periodic acid-Schiff stains, but attempts to isolate the etiologic agent at 25 and 37°C failed. DNA was directly extracted from tissue samples and the ribosomal genes ITS1-5.8S-ITS2 were partially sequenced. This revealed 99% identity to sequences from Ajellomyces capsulatus, the teleomorph of Histoplasma capsulatum, which was derived from a human case in Japan, as well as from horses from Egypt and Poland. Phylogenetic multi-locus sequence analysis demonstrated that the fungus in our case belonged to the Eurasian clade which contains members of former varieties H. capsulatum var. capsulatum, H. capsulatum var. farciminosum. This is the first study of molecular and phylogenetic aspects of H. capsulatum, as well as evidence for histoplasmosis farciminosi in a badger, further illuminating the role of this rare pathogen in Central Europe.