Granulomatosis with polyangiitis (GPA) is a rare ANCA-associated small-vessel vasculitis that predominantly affects the respiratory tract and kidneys, while cutaneous manifestations occur less frequently. Opportunistic fungal infections complicating GPA are uncommon, particularly involving rare filamentous basidiomycetes. We describe a 32-year-old male with a prolonged history of crusting rhinitis, tinnitus, and progressive nodular and ulcerative skin lesions on the trunk and extremities, accompanied by fever and lower limb edema. Laboratory evaluation revealed elevated inflammatory markers and positive c-ANCA (anti-PR3). Histopathology demonstrated granulomatous inflammation consistent with GPA. The clinical course was complicated by a secondary cutaneous infection caused by Hormographiella aspergillata, isolated from a skin lesion. Initial antifungal therapy with itraconazole was ineffective; subsequent treatment with voriconazole resulted in resolution of the fungal infection. The patient was then successfully treated with systemic immunosuppressive therapy, achieving long-term remission. To our knowledge, this is the first reported case of GPA complicated by a cutaneous infection with H. aspergillata. This case highlights the diagnostic challenges of GPA with atypical skin manifestations and underscores the importance of microbiological evaluation of skin lesions prior to initiating aggressive immunosuppressive therapy. KEYWORDS: granulomatosis with polyangiitis; ANCA-associated vasculitis; Hormographiella aspergillata; opportunistic fungal infection Granulomatosis with polyangiitis (GPA), formerly Wegener's granulomatosis, is a necrotizing granulomatous vasculitis affecting small to medium-sized blood vessels and belonging to the group of ANCA-associated vasculitides (AAV) (1). The disease is characterized by granulomatous inflammation, necrotizing vasculitis, and the presence of antineutrophil cytoplasmic antibodies, most commonly proteinase-3 ANCA (PR3-ANCA) (2). GPA may involve virtually any organ system, with predominant involvement of the upper and lower respiratory tract and kidneys (3). Cutaneous manifestations are reported in approximately 30-50% of patients and are usually associated with systemic disease activity (4). Opportunistic infections may complicate the course of GPA, particularly in the context of delayed diagnosis or immunosuppressive therapy. Infections caused by rare filamentous fungi such as Hormographiella (H) aspergillata are exceptionally rare and have predominantly been reported in immunocompromised patients with hematological malignancies (5, 6). A 32-year-old male was admitted with multiple painful ulcerations and nodules on the trunk and extremities, accompanied by high fever and marked bilateral lower limb edema. Four months before admission, nodular lesions on the left auricle and right nipple regressed spontaneously after purulent discharge. Six weeks prior to referral, painless nodules on the back and right upper arm were surgically incised and treated with antibiotics, followed by clinical deterioration with fever, progressive ulcerations, and painful swelling of the feet and ankles (figures 1a and !b). The patient had a two-year history of nasal obstruction, crusting rhinitis, and intermittent right-sided tinnitus. Rhinoscopy revealed mucosal thickening and septal perforation with crusts and synechiae. Dermatological examination showed deep ulcerations with yellow-brown crusts on the back, right upper arm, and left cheek (figures 1a and 1b). Laboratory evaluation demonstrated elevated inflammatory markers (ESR 76 mm/h, CRP 47.4 mg/L), hypoalbuminemia, and positive c-ANCA (anti-PR3). Initial microbiological cultures were sterile. Histopathology revealed granulomatous panniculitis with abscess formation. Fungal culture isolated H. aspergillata. Itraconazole therapy was ineffective; subsequent voriconazole treatment led to complete resolution of the cutaneous infection. Due to persistent systemic inflammation and c-ANCA positivity, the patient was treated with high-dose glucocorticoids and cyclophosphamide, which gradually led to completely remission of skin lesions (figure 2). Renal involvement developed during treatment, manifested as proteinuria. Long-term immunosuppressive therapy resulted in sustained remission with mild residual renal impairment. GPA is a rare multisystem autoimmune disease with heterogeneous clinical presentation, often leading to delayed diagnosis. Cutaneous involvement may be the initial manifestation and includes purpura, nodules, necrosis, and ulcerations, reflecting underlying vasculitis and granulomatous processes (2). In our patient, prominent skin lesions preceded the diagnosis by several months and contributed to diagnostic uncertainty. Opportunistic infections are a recognized complication in GPA, particularly following immunosuppression; however, fungal infections caused by filamentous basidiomycetes are exceedingly rare (5, 6). Hormographiella aspergillata, the anamorphic form of Coprinopsis cinerea, is an environmental fungus that has been implicated almost exclusively in invasive infections in patients with hematological malignancies, with reported mortality rates up to 70% (5, 6). To our knowledge, no previous case of GPA complicated by cutaneous infection with H. aspergillata has been reported. The present case underscores the importance of thorough microbiological evaluation of atypical or non-healing skin lesions in patients with suspected systemic vasculitis, particularly before initiation of intensive immunosuppressive therapy. Failure to recognize opportunistic infections may lead to significant morbidity and mortality. This case emphasizes the crucial role of dermatologists in the early recognition of systemic vasculitis presenting with skin manifestations. Comprehensive clinical, histological, and microbiological assessment is essential to establish the correct diagnosis and to identify rare infectious complications. Multidisciplinary management and careful monitoring are necessary to achieve long-term remission and to minimize treatment-related complications.
Dear editor, Haemangiomas are common benign vascular tumours usually detected on skin, mucosal surfaces, and soft tissues. In some extremely rare cases, haemangiomas can occur within a lymph node and as such are classified as primary benign vascular tumours of the lymph nodes, along with lymphangiomas, haemangioendotheliomas, and angiomyomatous hamartomas (1-2). A study reported that the overall prevalence of benign primary vascular intranodal tumours is only 0.3% (3). Even though intranodal haemangiomas are benign and usually asymptomatic, in clinical practice it is often challenging to differentiate them from primary malignant intranodal tumours or secondary malignancies. Herein, we describe a rare case of a femoral intranodal haemangioma in a melanoma high-risk patient, which was initially diagnosed as a melanoma metastasis. This appears to be the first reported instance of an intranodal haemangioma considered as a differential diagnosis of a melanoma metastasis. A 45-year-old female patient was admitted to our Clinic in June 2021 for a regular check-up after a melanoma excision on her left upper leg three years earlier. Histologically, it was a nodular melanoma of 6.22 millimetres Breslow thickness, Clark IV level, and 5 mitoses per square millimetre. Shortly after the primary excision and due to the unfavourable histopathological parameters, a preoperative positron emission tomography/computerized tomography (PET/CT) was done in which no pathological accumulation of radiopharmaceutical was observed. In histopathological findings of subsequently performed scar reexcision and left groin sentinel lymph node biopsy (SLNB), no tumour cells were detected. Since then, the patient had regular check-ups every few months in which all clinical, ultrasound, and laboratory findings were normal. A control PET/CT for this high-risk melanoma patient was done three years later, in June 2021. In comparison with the first PET/CT, a progression in size was observed in a hyperdense lymph node in left femoral region, diameter of 15 mm, now with increased accumulation of radiopharmaceutical (Figure 1). To exclude melanoma metastasis, an ultrasound of the left femoral region was done in which a well-defined, hyperechoic lesion with increased vascularity on colour Doppler was seen. As recommended by a radiologist and due to an unclear diagnosis, a excisional biopsy of the described femoral lymph node was conducted. Histopathological analysis revealed an oval, circumscribed vascular formation within most of the lymph node tissue (Figure 2a and 2b), predominantly composed of cavernous-like blood vessels and vascular spaces filled with erythrocytes and lined with thinned endothelium (Figure 2c and 2d). The lesion was sharply demarcated from the surrounding nodal tissue. No nuclear atypia or mitotic activity was observed. The described histopathological features led to a diagnosis of a primary intranodal haemangioma. At present, four years after the primary excision of melanoma and one year after the detection of intranodal haemangioma, the patient remains disease-free. Although lymph nodes frequently show extensive vascularity associated with many different infections and diseases, the verification of a primary vascular tumour in a lymph node is a very rare occurrence (6). Apart from Kaposi's sarcoma, only few examples of such intranodal vascular tumours have been reported, of which most of them were benign haemangiomas. Haemangiomas are ubiquitous tumours that can be found on skin, mucosa, and all internal organs, and are considered as the most common benign neoplasm of the liver. Histologically, there are 4 types of intranodal haemangiomas: capillary/cavernous, lobular, cellular, and epithelioid (1,6). Intranodal haemangiomas present as asymptomatic, solitary, palpable lymph nodes or as an incidental finding. They usually affect only one lymph node and rarely cause any functional impairment. In most of the previously published cases, intranodal haemangiomas have occurred within nodes of sites draining malignant tumours, i.e., after mastectomy following breast cancer diagnosis or salpingo-oophorectomy after ovarian cancer diagnosis (2,6,7). The treatment of primary lymph node haemangiomas includes surgical resection, which is considered curative (5,8,9). The prognosis is excellent, and the recurrence rate of these tumours has not been described (6,9). In our case, surgical extirpation was performed for the purpose of excluding metastatic disease. This appears to be the first reported instance of an intranodal haemangioma considered as a differential diagnosis of a melanoma metastasis. A causative relationship between melanoma and intranodal haemangioma has not been established but it is believed that these two lesions occur independently of each other. The identification of intranodal haemangiomas is important to avoid misdiagnosis as malignant vascular tumours, such as Kaposi's sarcoma or angiosarcoma, which are more common in lymph nodes. Since Kaposi's sarcoma can initially occur in lymph nodes, without the cutaneous involvement, this distinction requires special emphasis. Moreover, intranodal haemangiomas can also be suspected as secondary malignancies, especially in patients with high-risk malignant tumours, just like our patient was, so it is of great importance to think about intranodal haemangioma as a rare differential diagnosis of a lymphogenic metastasis.
Dear Editor, Genodermatoses are usually diagnosed in early childhood but diagnosis may be delayed in rare cases. Schöpf-Schulz-Passarge syndrome (SSPS) first described in 1971 is a rare type of autosomal recessive ectodermal dysplasia characterized by palmoplantar keratoderma, periocular and eyelid apocrine hidrocystomas, hypodontia, hypotrichosis, and nail dystrophy (1). Fewer than 40 cases have been reported up to 2018 (2) and the number has slightly increased with subsequent case reports. We report here a 73-year-old male patient whose parents were third-degree cousins presented to dermatology clinic for symptomatic palmoplantar hyperkeratosis (Figs 1a-1b) with a 30-years history. Physical examination determining mild alopecia (Fig. 1c), dental loss (Fig. 1d), micronychia (Figs 1e-1f) in association with numerous cystic lesions suggested the diagnosis of SSPS. Remarkably numerous hidrocystomas localized to the eyelids, periocular area, cheeks, nose, forehead, ears, shoulders, supraclavicular and axillary region showed three distinct morphologies; milia-like yellowish (Fig. 2a), bluish dome-shaped (Figs 2a-2b, 2d) and translucent (Fig. 2c) papular lesions. The histopatological examination determining the diagnosis of apocrine hidrocystoma (Figs 2e-2f) was followed by genetic confirmation of SSPS. A homozygous c.391G>A (p.Ala131Thr) variant was identified in WNT10A by Clinical Exome Sequencing. According to American College of Medical Genetics and Genomics criteria (3), this variant was classified as pathogenic (PS4, PM1, PM2, PM5, PP3, PP5). Rarely reported findings of SSPS including facial dysmorphism, loss of body hair (Fig. 2d), localized hyperhidrosis (Fig. 1f), generalized hypohidrosis, and atrophic tongue (Fig. 1d) was also associated. However, other rare supporting features, such as eccrine syringofibroadenoma, rosacea-like facial erythema, hypoplastic areolae and nipple, and ocular involvement were not observed (4-7). The patient had also a basal cell carcinoma on the nose (Fig. 2c) which has been occasionaly reported in SSPS (4). Furthermore, a 9 × 9 cm soft, subcutaneous mass located on the midline of the lumbar region, clinically suggestive of a lipoma, was also noted. In our case, although dental loss was the earliest presenting feature, major manifestations such as periocular and eyelid apocrine hidrocystomas and palmoplantar keratoderma emerged initially after the 5th decade, leading to a delay in diagnosis. Whereas extraocular localizations of apocrine hidrocystoma is described in sporadic cases (8), it has not been highlighted in the context of SSPS. Our patient, however, exhibited numerous lesions in multiple additional sites including the nose, cheeks, forehead, external ears, upper trunk and axillae, broadening the recognized clinical distribution of this hallmark finding. A noteworthy finding in this patient was the concurrent presence of three morphologically distinct types of facial apocrine hidrocystomas. While a review of previously reported cases revealed that lesions with different morphologies can coexist in individual patients (2), this phenotypic diversity has rarely been explicitly highlighted in the literature. WNT10A mutations, inherited in an autosomal recessive manner, have been documented in both homozygous and compound heterozygous states (7, 9). These mutations can result in a wide phenotypic spectrum, ranging from isolated hypodontia and oligodontia to more complex ectodermal dysplasia syndromes such as odonto-onycho-dermal dysplasia (OODD) and SSPS (5, 6, 9). On the other hand some authors suggest that these two conditions may represent phenotypic variations of the same underlying genetic defect rather than distinct entities (10). While our patient exhibited overlapping features with OODD, including hypodontia, palmoplantar hyperkeratosis, hypotrichosis, and nail dystrophy, the presence of numerous apocrine hidrocystomas was distinctive for SSPS (5)D. In conclusion, SSPS can be recognized even decades after onset of the mild dermatological manifestations (2). Awareness of the rich clinical spectrum of apocrine hidrocystomas as they are not limited to eyelids or periocular area and present with papulonodules in different size and color may be crucial (5)D. Although a therapeutic option for SSPS still does not exist timely recognition may prevent unnecessary diagnostic and therapeutic interventions and enable appropriate genetic counseling of the family members.
Sweet's syndrome (acute febrile neutrophilic dermatosis) is an inflammatory condition characterized by the abrupt onset of erythematous, oedematous plaques or nodules and a dense neutrophilic dermal infiltrate. Although usually associated with fever and tender lesions on the face and upper extremities, its clinical spectrum is broad, and atypical presentations may pose diagnostic challenges. We report the case of a 50-year-old female patient who presented with an acute eruption of widespread, annular, erythematous, and oedematous plaques predominantly involving the trunk and extremities, accompanied by severe pruritus. The patient denied fever or other systemic symptoms. Laboratory investigations demonstrated marked leukocytosis with neutrophilia and elevated inflammatory markers. An extensive infectious, immunological, and malignancy workup was unremarkable. Histopathological examination revealed a dense neutrophilic dermal infiltrate with leukocytoclasia in the absence of true vasculitis, consistent with Sweet's syndrome. Direct immunofluorescence was negative. The patient reported a history of similar episodic eruptions over two decades, often temporally associated with respiratory infections. Systemic glucocorticoid therapy led to rapid clinical improvement and normalization of inflammatory parameters, with complete resolution at follow-up. This case highlights the clinical heterogeneity of Sweet's syndrome, demonstrating that prominent pruritus, truncal predominance, and afebrile presentation may occur. Recognition of atypical manifestations is essential to avoid misdiagnosis, particularly with urticarial or allergic disorders. Thorough evaluation for associated systemic disease and careful documentation of recurrent patterns remain crucial. Early histopathological confirmation and prompt initiation of appropriate therapy enable rapid disease control and favourable outcomes.
Folliculitis decalvans, typically observed in adult males, is rare in pediatric populations. This case report explores the diagnosis and management of a 12-year-old boy with this condition, marking a rare pediatric case in Greece. The patient, a 12-year-old boy of Greek descent, initially presented with symptoms of hair loss beginning at three years of age. Over the years, he developed alopecic patches on the scalp characterized by perifollicular erythema, hyperkeratosis, and tufted hair, accompanied by mild itching and discomfort The report discusses the diagnostic challenges (dermoscopy, histological examination), treatment strategies, and the patient's response to a multimodal treatment regimen.
