UNASSIGNED: Fungal infections in neonates, particularly primary cutaneous aspergillosis (PCA), pose significant risks to premature infants with very low birth weight. This report chronicles the case of a 22-week gestational age female, with a birth weight of 430 g, who developed extensive cutaneous aspergillosis leading to extremity compartment syndrome- a first in the medical and surgical literature.
METHODS: A female micro preemie born at 22 weeks and 2 days was critically ill during her first week of life. On first day of life, attempts were made to establish intravenous access in all extremities. Eventually, the neonatal team established a peripherally inserted central catheter (PICC) in the left upper extremity. She had surfactant therapy due to lung immaturity and was on high frequency oscillatory ventilation. A large patent ductus arteriosus was treated soon after birth with intravenous acetaminophen. On day seven of life, she developed skin blisters rapidly progressing to necrotic eschars, particularly on the right lower extremity, leading to compromised limb circulation. Consultations with pediatric surgery and orthopedics one week later resulted in bedside medial and lateral escharotomies to salvage the limb. Tissue biopsy confirmed Aspergillus species, prompting a dual antifungal treatment with liposomal Amphotericin B and Voriconazole. The lesions gradually resolved with diligent wound care and aggressive physical therapy, yet a residual contracture of the right foot\'s dorsal area persisted, necessitating splinting.
UNASSIGNED: Over the course of treatment, her cutaneous lesions resolved, and no further debridement was required. Aggressive physical therapy was initiated for residual contractures that the infant developed due to full thickness necrosis of the cutaneous infection. Due to concurrent pulmonary complications and tracheomalacia, surgical intervention for the contracture has been postponed.
CONCLUSIONS: This case highlights the critical importance of early detection and treatment of PCA in preterm infants, the challenges in managing complex cases in the NICU and the need for a multidisciplinary approach to care.

Primary cutaneous aspergillosis (PCA) is a rare opportunistic infection caused by Aspergillus that can be life-threatening. PCA is mainly reported in immunocompromised hosts such as patients with AIDS, those with hematologic malignancy, or infants with occlusive dressings. However, no study has previously reported PCA associated with toxic epidermal necrolysis (TEN). This study reports four cases of TEN complicated with PCA, presenting with discrete gray or black spots over newly formed epithelia. Risk factors of PCA in patients with TEN include host factors, iatrogenic factors, indoor environment, and wound care. Two of the four cases eventually died, highlighting the importance of further exploring PCA in patients with TEN.

Aspergillosis of the newborn remains a rare but severe disease. We report four cases of primary cutaneous Aspergillus flavus infections in premature newborns linked to incubators contamination by putative clonal strains. Our objective was to evaluate the ability of matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) coupled to convolutional neural network (CNN) for clone recognition in a context where only a very small number of strains are available for machine learning. Clinical and environmental A. flavus isolates (n = 64) were studied, 15 were epidemiologically related to the four cases. All strains were typed using microsatellite length polymorphism. We found a common genotype for 9/15 related strains. The isolates of this common genotype were selected to obtain a training dataset (6 clonal isolates/25 non-clonal) and a test dataset (3 clonal isolates/31 non-clonal), and spectra were analysed with a simple CNN model. On the test dataset using CNN model, all 31 non-clonal isolates were correctly classified, 2/3 clonal isolates were unambiguously correctly classified, whereas the third strain was undetermined (i.e., the CNN model was unable to discriminate between GT8 and non-GT8). Clonal strains of A. flavus have persisted in the neonatal intensive care unit for several years. Indeed, two strains of A. flavus isolated from incubators in September 2007 are identical to the strain responsible for the second case that occurred 3 years later. MALDI-TOF is a promising tool for detecting clonal isolates of A. flavus using CNN even with a limited training set for limited cost and handling time.
Cutaneous aspergillosis is a rare but potentially fatal disease of the prematurely born infant. We described here several cases due to Aspergillus flavus and have linked them to environnemental strains using MLP genotyping and MALDI-TOF mass spectrometry coupled with artificial intelligence.

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.

UNASSIGNED: Aspergillosis is an uncommon fungal infection in which primary cutaneous sites are very rare, and most cases occur in patients with immunocompromised status. Although primary cutaneous aspergillosis is usually encountered in immunocompromised patients, it also occurs in immunocompetent individuals.
UNASSIGNED: We report a case of primary cutaneous aspergillosis in a 46-year-old immunocompetent woman with diabetes mellitus after tattooing. She presented with erythematous papules, papulopustules and a plaque on the right lower limb of more than two years duration which had failed to respond to antihistamine treatment. Histological examination of a skin biopsy sample showed oval spores in the corneous layer, a slightly thickened epidermis, and infiltrating lymphocytes and neutrophils around the blood vessels in the superficial dermis. Aspergillus fumigatus was isolated and identified in cultures. Clinical and biological examinations did not reveal any systemic localization of aspergillosis, ruling out a hypothesis of blood dissemination. Lesions resolved completely after systemic antifungal treatment with itraconazole.
UNASSIGNED: Clinical lesions of primary cutaneous aspergillosis are nonspecific and usually present as a variety of lesions, including macules, papules, nodules, plaques, purpura, blood blisters, and pustules. The nonspecific features and variety of lesions can lead to misdiagnosis and delayed treatment. Direct microscopy, microbiological culture, and histopathological examination are helpful for diagnosing primary cutaneous aspergillosis. Moreover, the physicians should be aware of the possibility of Aspergillus infection in tattooed cases.

Aspergillosis is a systemic fungal infection that commonly affects immunocompromised individuals and, less frequently, immunocompetent individuals. It is the most common opportunistic fungal disease after candidiasis. This is primarily a pulmonary infection and can also involve other body sites like paranasal sinuses and cutaneous tissues. Aspergillus fumigatus , Aspergillus niger , and Aspergillus flavus are the common species infecting humans. Primary cutaneous aspergillosis (PCA) is usually caused by A. flavus and A. fumigatus . It is commonly seen in immunocompromised patients such as those suffering from diabetes, malignancies, tuberculosis, human immunodeficiency virus, or patients on long-term steroids and antibiotics. In this article, we report a case of PCA, in the immediate postoperative period, following a road traffic accident, in an immunocompetent patient. This posed a diagnostic challenge to the treating physicians. A. flavus was confirmed with 10% potassium hydroxide mount, lactophenol cotton blue, and growth on Sabouraud dextrose agar from tissue culture sample. Antifungal treatment was initiated with oral itraconazole 200 mg after performing antifungal susceptibility testing based on Clinical and Laboratory Standards Institute guidelines. The patient\'s condition improved and was discharged. Thus, early detection of PCA combined with medical and surgical intervention can successfully eradicate infection and help in preventing disseminated aspergillosis.

We describe a case of primary cutaneous aspergillosis caused by Aspergillus fumigatus, and elucidate the underlying genetic and immunological mechanisms.
Routine clinical and laboratory investigations were performed. Whole-exome sequencing of the patient\'s DNA suggested the presence of a CARD9 mutation, which was confirmed by Sanger sequencing. Innate and adaptive immunological responses of patient-derived CARD9-deficient cells were evaluated with ELISA and flow cytometry. Cutaneous and pulmonary aspergillosis models were established in Card9 knockout (KO) mice, which were compared with wild-type and immunosuppressed mice, to explore the pathogenesis and Aspergillus susceptibility.
A 45-year-old man presented with a 37-year history of skin lesions on his face. A diagnosis of primary cutaneous aspergillosis was made through histopathology, immunohistochemistry, and tissue culture. Sanger sequencing of CARD9 showed a homozygous frame-shift mutation (c.819_820insG, p.D274fsX60), which led to the lack of CARD9 expression. Peripheral blood mononuclear cells from the patient showed selective impairment of proinflammatory cytokines, and Th1-, Th17-, and Th22-associated responses upon fungus-specific stimulation. The cutaneous aspergillosis model established in Card9 KO mice presented with persistent infection, with fungal germs and short hyphae in tissue, consistent with the patient\'s lesions. Skin lesions in immunosuppressed mice were more severe, and led to death. Unlike our patient, Card9 KO mice were relatively susceptible to pulmonary aspergillosis, with reasons to be investigated.
This is, to our knowledge, the first report that links cutaneous aspergillosis to CARD9 mutation. This work enriches both the phenotypic spectrum of CARD9 deficiencies and the genetic background of cutaneous aspergillosis.

Primary cutaneous aspergillosis is a rare, life-threatening fungal infection in premature infants. We report a case of primary cutaneous aspergillosis caused by Aspergillus tamarii in an extremely low birthweight infant. The infant was delivered by cesarean section with complications from an intrauterine infection, brain intraventricular hemorrhage, tension pneumothorax and cardiac tamponade. On the 12th day of life, he developed erythematous maceration with erosion on his back. Septate hyphae were detected on two occasions from specimens of the skin lesion. The manifestations of the colony and slide culture showed the characteristics of A. tamarii. The nucleotide sequences of internal transcribed spacer regions of the ribosomal RNA gene, partial sequences of β-tubulin and calmodulin gene were compatible with those of A. tamarii. Of the known Aspergillus species, Aspergillus fumigatus and Aspergillus flavus have been reported in previous studies as the major causative agents in primary cutaneous aspergillosis, whereas human infection by A. tamarii is rare. We consider that A. tamarii is important as an unusual opportunistic human pathogen among premature infants.

Primary invasive cutaneous aspergillosis is a rare fungal infection that occurs mostly in immunocompromised patients. Newborns of very low birth weight present a high risk for this type of infection due to an immaturity of the cutaneous barrier and of the immune system.
We describe here a case of simultaneous invasive cutaneous aspergillosis in two preterm twins. Two male preterm bichorionic biamniotic twins (A & B) were born at a general hospital by spontaneous normal delivery at 24 weeks and 6 days of gestation. They were transferred to our hospital where they receive surfactant, antibiotics and hydrocortisone. Six days later, twin A showed greenish lesions in the umbilical region. The spectrum of antibiotic therapy was broadened and fluconazole was added. The umbilical catheters of the two twins were removed and replaced by epicutaneo-cava venous catheters and the cultures were positive for Aspergillus fumigatus. Fluconazole was replaced in both twins by liposomal amphotericin B and the incubators were changed. The serum galactomannan was also positive for both twins. At day 10, yellowish lesions appeared in the abdominal region in twin B. He died on day 18 following complications related to his prematurity. Concerning the twin A, serum galactomannan was negative on day 30; liposomal amphotericin B was stopped 1 week later, with a relay by econazole (cream). His condition improved and on day 66 he was transferred for follow-up at the general hospital where he was born.
The source of contamination by A. fumigatus was not identified, but other similar cases from the literature include construction work at or near the hospital, oximeter sensors, latex finger stalls, non-sterile gloves, humidifying chambers of incubators, bedding and adhesive tapes. The skin fragility of preterm newborns is an excellent potential entry point for environmental fungal infections. These cases highlight the importance of suspecting primary cutaneous aspergillosis in extremely low birth weight neonates with rapidly progressive necrotic lesions.