To emphasize the diagnostic value of cutaneous manifestations in disseminated invasive fungal disease (IFD). IFD carry high mortality and diagnosis isoften delayed, while early recognition is crucial for patient outcomes. This review focuses on skin manifestations of fungi of highest relevance according to the WHO: Candida spp., Aspergillus spp., Mucorales, Fusarium spp., and Scedosporium spp. Cutaneous signs in disseminated candidiasis typically manifest as maculopapular or nodular lesions. Frequency and morphology vary depending on the Candida spp. involved. Secondary cutaneous aspergillosis presents with variable morphologies, including erythematous papules, ulcerative nodules, hemorrhagic bullae, or necrotic eschars, and may appear before standard diagnostic tests yield positive results. In invasive fusariosis, lesions typically present as vesicles or papules and progress to necrotic eschars. The morphology of skin manifestations of generalized mucormycosis varies according to the underlying disease. The formation of a necrotic eschar is considered pathognomonic. In disseminated scedosporiosis, cutaneous manifestations include ecchymoses, hemorrhagic bullae, necrotic papules, ulcers, or infiltrative plaques, often resembling infections with aspergillosis or fusariosis. Diagnosis requires a multimodal approach combining histopathology, microbiological cultures and nonculture-based assays. Despite the variability in frequency and presentation, cutaneous manifestations provide a valuable clinical clue in disseminated IFD and may facilitate early recognition and intervention.

Introduction Invasive aspergillosis is a severe infection that usually affects immunocompromised patients. Primary cutaneous involvement is a rare presentation and presents a challenge for early diagnosis. We report a case of primary cutaneous aspergillosis (PCA) in an immunocompromised patient with no evident prior skin trauma and with pulmonary dissemination. Case report We report the case of primary cutaneous aspergillosis involving the left ankle in a 5-year-old girl with no history of preceding trauma. The patient was undergoing chemotherapy for lymphoblastic leukemia. Aspergillus hyphae were identified on skin biopsy. Cultures grew Aspergillus flavus. The diagnosis of cutaneous aspergillosis enabled the diagnosis of probable pulmonary aspergillosis, although there was no mycopathological proof of lung infection. The patient was treated with initial Amphotericin B followed by Voriconazole with complete skin and respiratory response. Conclusion This case underscores the critical need to consider cutaneous aspergillosis in immunocompromised patients with necrotic skin lesions— even in the absence of obvious trauma—as prompt diagnosis and treatment are vital to prevent dissemination and and improve outcomes.

Masked Menace: Primary Cutaneous Aspergillosis Disguised as a Ganglion Cyst in an Immunocompetent Rheumatoid Arthritis Patient

Primary cutaneous aspergillosis is a rare fungal infection in extremely preterm neonates. We report a male infant born at 25+5 weeks' gestation who developed necrotic lesions at the site of an umbilical catheter covered with an occlusive dressing. Culture confirmed Aspergillus fumigatus, and systemic liposomal amphotericin B combined with local enzymatic debridement and a non-adherent silicone wound contact layer was initiated after receipt of the culture result. The lesions resolved completely, leaving only a fine residual scar without functional impairment.This case emphasises the importance of early recognition, culture-based diagnosis and timely antifungal therapy in preterm neonates with catheter-related skin lesions, even when standard antifungal prophylaxis has been administered.

Primary cutaneous aspergillosis (PCA) is a rare form of Aspergillus infection that usually affects immunocompromised people. However, it also occurs in healthy individuals, where it is often mistaken for common dermatophyte infections. We describe a case of a 27-year-old woman, with a normal immune system, who developed persistent, itchy, red to darkened patches on both lower legs for over two years. Initial examination and KOH microscopy suggested tinea corporis. Despite using oral antifungal medications and topical urea cream, the lesions only improved slightly. A fungal culture later identified Aspergillus niger as the cause. She was treated with 200 mg of oral itraconazole daily and topical urea cream, resulting in significant improvement after eight weeks. PCA in patients with healthy immune systems is rare and often results from minor, unnoticed trauma introducing fungus. Although A. fumigatus and A. flavus are more common causes, A. niger is an uncommon culprit. This case highlights the diagnostic difficulties of PCA given its resemblance to a dermatophyte infection. Fungal culture is an important diagnostic step, if available. Healthcare providers should think about PCA in unusual or long-lasting skin conditions that do not respond to treatment, even in healthy individuals, to ensure quick diagnosis and proper antifungal therapy management.

Abstract A common fungal infection in immunocompromised patients is aspergillosis. Ubiquitous soil-and water-dwelling saprophytes of the genus Aspergillus are the causative organisms. Aspergillus fumigatus is responsible for 95% of human infections. A. fumigatus and Aspergillus flavus are the common causative organisms of the rare primary cutaneous disease. We present a case of primary cutaneous aspergillosis caused by A. flavus in a renal allograft recipient. Our patient was a 32-year-old live donor renal allograft recipient, on triple immunosuppression with tacrolimus, mycophenolate mofetil, and prednisolone along with antithymocyte globulin induction at 4 mg/kg. The patient presented with a gradually increasing swelling over the medial aspect of the left foot. Local examination revealed a single verrucous hyperpigmented plaque with erythematous base observed over the right medial malleolus, measuring around 4 cm × 3 cm. The diagnosis of A. flavus was confirmed on histopathological examination, and tissue culture of the punch biopsy was obtained from the site of the lesion. The patient was managed with surgical debridement and debulking, followed by oral voriconazole for 8 weeks, which is the standard management protocol for cases of primary cutaneous aspergillosis.

Primary cutaneous aspergillosis (PCA) is an uncommon manifestation of Aspergillus infection, typically occurring in immunocompromised individuals. We report a rare case of diffuse PCA in an immunocompetent patient who presented with multiple painless, discharging nodular lesions on the extremities over a 3-month period. Clinical examination revealed multiple nontender swellings with erythema, edema, desquamation, and purulent discharge. Direct microscopy with potassium hydroxide mount revealed thin septate hyphae with acute-angle branching. Fine-needle aspiration cytology and histopathology confirmed fungal elements consistent with Aspergillus. Fungal culture from the biopsy specimen yielded Aspergillus flavus. Based on clinical, cytological, histopathological, and microbiological findings, a diagnosis of PCA was established. The patient was treated with oral itraconazole 200 mg daily but was lost to follow-up. This case highlights the importance of considering fungal infections like PCA in immunocompetent individuals, especially when faced with atypical, nonhealing cutaneous lesions. Early recognition and appropriate antifungal therapy are crucial to prevent potential complications and dissemination.

Primary cutaneous aspergillosis can disseminate in premature infants. Voriconazole, dosed every 12 hours, is the preferred antifungal agent. Prior studies show difficulty achieving therapeutic targets with this regimen. We report the safety and attainment of therapeutic targets with voriconazole dosed q8h with careful therapeutic drug monitoring. Retrospective review of 4 extremely premature infants with primary cutaneous aspergillosis given voriconazole divided every 8 hours with therapeutic drug monitoring. Demographics, voriconazole administration, treatment duration, need for debridement and patient outcomes were analyzed. All patients survived with complete healing of affected skin. Median voriconazole duration was 69.5 days (min-max 36-84); 69% of voriconazole troughs on intravenous therapy were within the targeted range (1-5 mcg/mL). Troughs on enteral voriconazole were consistently under the targeted range. Few mild, transient adverse effects attributable to therapy were noted. Intravenous voriconazole every 8 hours was safe and consistently met therapeutic targets. Enteral administration consistently failed to achieve therapeutic concentrations.

Abstract Introduction: Aspergillus, a filamentous fungus ubiquitous in the environment, infects primarily immunocompromised or chronic pulmonary disease patients. Its manifestations vary by immune status, from aspergilloma to invasive rhinosinusitis and bronchopulmonary aspergillosis. Pulmonary infections can disseminate hematogenously, with rising invasive cases noted in hospitalized patients, including those with severe COVID-19. Case: A 67-year-old female with a history of extensive deep venous thrombosis of the right popliteal veins, atrial fibrillation post-cardioversion on apixaban, tachycardia-induced cardiomyopathy, COPD on home oxygen, rheumatoid arthritis on prednisone, and chronic kidney disease IIIB (baseline Cr 1.6), presented from a nursing facility for hypoxia and leukocytosis, unresponsive to outpatient therapy with azithromycin, doxycycline, and increased prednisone. She reported a three-week history of productive cough and dyspnea. On arrival, she was afebrile, blood pressure 89/62 mmHg, pulse 85 bpm, respirations 20, and saturating 89% on 4L nasal cannula. Initial workup showed WBC 31,000 (91% neutrophils), BUN 89, Cr 2.2, CRP 9.8, and BNP 100. COVID-19 and RSV tests were negative, and procalcitonin was 0.31. Chest CT revealed bilateral diffuse patchy ground-glass opacities with peripheral bronchiolar dilatation and interstitial prominence. She was admitted for acute-on-chronic hypoxic respiratory failure secondary to multifocal pneumonia and COPD exacerbation, was started on ceftriaxone, methylprednisolone, and nebulizations. A non-infectious workup was initiated, and blood cultures remained negative. Respiratory cultures grew Aspergillus fumigatus, and elevated Aspergillus flavus IgE (1.73) raised concern for invasive aspergillosis. Initially treated with amphotericin B due to potential interactions of azole antifungals with amiodarone, later transitioned to oral isavuconazonium (Cresemba). Her course was complicated by new hemorrhagic lesions on her extremities, evolving into bullae and ulcers. Skin biopsy confirmed cutaneous aspergillosis. Despite initial improvement, she experienced recurrent respiratory failure and frequent readmissions. Ultimately, she transitioned to comfort care and passed away. Discussion: Untreated, invasive aspergillosis has a 100% mortality rate, reduced to 20% at six weeks with antifungal treatment. CNS dissemination remains universally fatal, highlighting the need for swift diagnosis and intervention. Growth of Aspergillus in sputum or lavage suggests infection, but tissue sampling is necessary for confirmation. Bronchoscopy and chest CT assess disease severity. Serum galactomannan aids diagnosis in hematologic and transplant patients. Our patient's chronic obstructive pulmonary disease and chronic steroids use put her at an elevated risk. Cutaneous aspergillosis in our patient is thought to be secondary to hematogenous spread from pulmonary infection, given the late onset of presentation. Voriconazole is the preferred treatment, alternatives are isuvaconazole and amphotericin B.

A 49-year-old man presented for immunologic evaluation due to recurrent infections since childhood. He had frequent staphylococcal skin infections related to minor skin trauma, including forceps used during delivery, but no abscesses requiring drainage. He was first hospitalized as a teenager with lymphadenitis and pneumonia. At 21 years, he had spontaneous splenic rupture requiring splenectomy. At age 25, he was hospitalized with pulmonary nocardiosis. At age 30, he was hospitalized with pulmonary aspergillosis for the first time. By the time of presentation, he had five episodes of pulmonary aspergillosis and one episode of cutaneous aspergillosis, each treated with prolonged courses of antifungals. He had not received antimicrobial prophylaxis outside these treatment courses. He continued to have bacterial pneumonias, cellulitis, and onychomycosis throughout adulthood. In his early 40s, he developed a chronic cough and dyspnea. A lung biopsy demonstrated noncaseating granulomas, favored to be hypersensitivity pneumonitis. His symptoms were controlled with mycophenolate monotherapy for two years until he stopped taking it and subsequently required chronic corticosteroids. Given the recurrent Aspergillus infections, a neutrophil oxidative burst was sent and found to be 7%, raising concern for chronic granulomatous disease (CGD). He had no family history of immunodeficiency. Further immunologic evaluation revealed normal quantitative immunoglobulins with protective levels of tetanus, diphtheria, and pneumococcal titers, and normal lymphocyte subsets. Repeat neutrophil oxidative burst was 1.3% with a normal control. Genetic testing for inborn errors of immunity was negative, including CGD-associated genes CYBB, CYBA, NCF2, and NCF4. Daily antifungal and antistaphylococcal prophylaxis were started. This case highlights a late diagnosis of CGD in the 5th decade of life. His infectious pattern was relatively mild until his 20s, when he began to have recurrent pulmonary infections with catalase-positive organisms, possibly due to some residual NADPH oxidase function. The mean age of diagnosis for X-linked CGD is 3 years, while the autosomal recessive form is diagnosed at a mean age of 7.8 years. Interestingly, initial genetic testing for this patient was negative, despite his phenotype being consistent with CGD and repeatedly abnormal oxidative burst. Additional testing, including NCF1, is being sent to further evaluate for a monogenic cause.

Cutaneous aspergillosis is a fungal infection caused by multiple genera of Aspergillus. Primary cutaneous Aspergillosis is associated with an immunocompromised state, with prior history of traumatic inoculation. This case report highlights the atypical nodular presentation of Primary cutaneous aspergillosis, contrary to its typical presentation of an ulcer or eschar and its need to be evaluated thoroughly for effective management. Early diagnosis of Primary cutaneous aspergillosis poses a challenge, but a comprehensive approach combining appropriate antifungal therapy with meticulous assessment for adjunctive surgical interventions shows promise in improving patient outcomes. Such an approach not only reduces the risk of systemic spread but also enhances the likelihood of achieving a definitive cure.

The aim of this study is to share our experience regarding the diagnosis and therapeutic management of primary cutaneous aspergillosis (PCA) in the burn patient, an uncommon infection associated with increased mortality, morbidity, and treatment costs. The uniqueness of this article is the presence of PCA in pediatric patients where the Meek micrografting technique was used. We performed a retrospective study from June 2020 to November 2024. The inclusion criteria were the concomitant presence of burn injuries and confirmed PCA. We identified six patients, aged between 12 and 17 years, admitted with deep burns ranging from 55% to 90% of the total body surface area (TBSA). They required complex ICU treatment and underwent extensive excision-grafting surgeries. The suspicion of infection was raised by changes in the appearance of wounds. Systemic and topical antifungal treatment was established in patients after a PCA diagnosis. Five out of the six cases had a favorable outcome. The use of the Meek micrografting technique in burn treatment represents a new challenge in the treatment of PCA due to the polyamide gauze that covers the micrografts. Early detection and appropriate topical antifungal agents combined with systemic treatment may save the infected grafts and limit the infection spread without necessarily removing the polyamide gauze.

Fungal infections are associated with high risk of morbidity and mortality in the neonatal population. Infants who are premature and extremely low birth weight (ELBW) are at increased risk for fungal infections due to their fragile skin barrier, immature immune systems, disruption of normal flora with antibiotic exposure, presence of central catheters, and corticosteroid use. In neonates, most invasive fungal infections are caused by the Candida species. Infections from other fungal species, such as Aspergillus, are rare. The case presented in this article describes an infant who is ELBW born at 23 weeks' gestation and their course with severe cutaneous A. fumigatus infection requiring multiple surgical debridement procedures. These fungal infections require a high index of suspicion for prompt identification and early treatment. Primary cutaneous aspergillosis should be suspected in high-risk infants with rapidly progressive ulcerative or necrotic skin lesions. [Pediatr Ann. 2025;54(4):e130-e134.].

Primary cutaneous aspergillosis secondarily invasive in an immunocompromised patient: A case report and literature review

Fungal infections in preterm infants are uncommon but serious infections that carry a high mortality rate. Preterm infants who are extremely low birth weight are at high risk for fungal infections due to immaturity of their immune system and skin barrier. Factors which further reduce host immunity in premature infants include prolonged use of broad-spectrum antibiotics and corticosteroids. Our case presentation involves an extremely low-weight 23-week preterm infant diagnosed with primary invasive cutaneous aspergillosis (PCA) confirmed by skin biopsy and cultures obtained from skin debridement. His inoculation was thought to be secondary to either a thermal burn or macerated skin from prolonged incubation. This case highlights the importance of keeping fungal infections at the forefront of one's differential diagnosis when an extremely low-weight infant presents with cutaneous lesions, as disseminated fungal infections carry a high mortality rate.

714 Primary cutaneous aspergillosis in extremely premature neonates: a case series

Primary cutaneous aspergillosis (PCA) is a rare disease caused by a few pathogenic species of Aspergillus. It manifests in immunocompromised patients as different types of localised lesions, the treatment has evolved and the latest reviews ensure better results with a combined therapy. We present a 27-year-old male gardener with a history of human immunodeficiency virus infection and a nodular presentation of PCA. He received surgical and antifungal medication, showing a good response and no dissemination or recurrence of the disease.

Aspergillosis is a severe and fatal complication that causes infection in transplant recipients and patients with immunodeficiency syndrome, neutropenia, chronic granulomatosis, and hematologic malignancies. Invasive Aspergillosis has been reported as one of the fungal infections with high mortality in transplant recipients. This study aimed to describe the manifestations, prevalence, management and outcome of invasive Aspergillosis fungal infections in liver transplant patients. This descriptive cross-sectional study was conducted on patients with liver transplantation who were infected with invasive Aspergillosis fungal infections. The data were extracted from the medical records of the archive of Montasryieh Hospital, Mashhad, Iran, between August 2019 and August 2020. In general, 86 patients who had liver transplantation were hospitalized at Montasryieh Hospital from August 2019 to August 2020. Among them, 10 patients were infected with invasive Aspergillosis. Only 6.7% of the patients were categorized under late-onset (> 90 days after liver transplantation), and 93.3% of them were early-onset (< 90 days after liver transplantation). Invasive Aspergillosis fungal infections were suspected based on clinical or radiological signs (possible in 30% of cases; n = 3). The probable diagnosis was reported in 60% (n = 6), and the proven diagnosis was observed only in one patient. In addition, 80% of the patients were diagnosed with Pulmonary Aspergillosis, and two patients had pulmonary Aspergillosis in combination with the central nervous system and cutaneous Aspergillosis. A correlation was found between a comorbid disease and the type of Aspergillosis (r = 0.69; P = 0.02). Voriconazole was effective to treat invasive Aspergillosis in all patients. The prevalence rate of Aspergillosis is relatively high among liver transplant recipient populations (11%). All recipients infected with Aspergillosis had at least one risk factor, including an underlying disease. It seems that Voriconazole therapy is effective among transplant patients with pulmonary Aspergillosis.

Aspergillosis is a fungal infection, usually affecting the lungs, mostly in immunocompromised patients. Musculoskeletal or cutaneous involvement is extremely rare and when it does occur, the diagnosis and treatment is delayed. We present a case of primary cutaneous aspergillosis presenting as a cyst in the foot of a 54-year-old immunocompetent female. She presented with the complaint of painful lump over right foot at the region of the fourth webspace. Magnetic Resonance Imaging (MRI) was suggestive of infected ganglion cyst. However, histopathological examination showed granulomas with areas of caseous necrosis and silver stain showed multiple fungal hyphae with morphology suggestive of Aspergillus species.

Select Aspergillus species can produce oxalate as a fermentation byproduct, which may react with calcium ions to produce insoluble calcium oxalate crystals in tissues. These crystals are frequently associated with pulmonary Aspergillus infections, yet are rarely described in primary cutaneous aspergillosis. Herein, we report the presence of calcium oxalate crystals detected on cutaneous specimens from primary cutaneous Aspergillus niger and Aspergillus fumigatus infections in an immunocompromised, premature infant. No metabolic sources of oxalosis were found.