Clinical Scorecard: Skin Biopsy as a Diagnostic Tool in Fatal Histoplasmosis-Associated Hemophagocytic Lymphohistiocytosis: A Case Report
At a Glance
Category
Detail
Condition
Fatal histoplasmosis-associated secondary hemophagocytic lymphohistiocytosis (HLH) in a case report.
Key Mechanisms
The article describes HLH as a hyperinflammatory syndrome involving uncontrolled activation of cytotoxic lymphocytes and macrophages, producing multiorgan injury; disseminated histoplasmosis is a recognized infectious trigger.
Target Population
The reported patient was a 41-year-old man with psoriasis treated with adalimumab who developed histoplasmosis-associated HLH.
Care Setting
Tertiary-center hospital evaluation of suspected HLH and systemic infection, including dermatologic assessment and biopsy of newly recognized papules.
Key Highlights
The patient receiving adalimumab met HLH-2004 criteria in at least six domains.
Bone marrow fungal stains were negative, while a skin biopsy of subtle acneiform papules showed numerous invasive organisms.
Urine Histoplasma antigen was positive; the patient also had markedly elevated serum beta-D-glucan and positive Aspergillus galactomannan assays.
The case report describes fatal histoplasmosis-associated HLH; etoposide was planned but withheld because of severe gastrointestinal hemorrhage.
Guideline-Based Recommendations
Diagnosis
The authors state that HLH evaluation should account for suspected trigger and type of immunosuppression; they note that TNF-α inhibitor exposure increases concern for invasive fungal infection.
In this case, dermatologic assessment and biopsy of subtle papules identified invasive organisms after bone marrow fungal stains were negative.
Skin-specimen molecular testing identified Histoplasma capsulatum, according to the case report.
Management
The case report describes dexamethasone, ruxolitinib, and one dose of rituximab; low-level EBV viremia was also reported.
Etoposide was planned but withheld because of severe gastrointestinal hemorrhage.
Liposomal amphotericin B was included in the reported management; the supplied excerpt does not establish its dose or subsequent course.
Monitoring & Follow-up
The report documents monitoring of blood counts, liver and coagulation measurements, triglycerides, fibrinogen, ferritin, and soluble interleukin-2 receptor.
Final natural killer cell function and HLH genetic panel results were not available in the medical record.
Risks
The article states that TNF-α inhibition increases the risk of severe or disseminated histoplasmosis, including outside traditionally recognized endemic regions.
The introduction identifies infection, malignancy, autoimmune disease, and immunosuppressive therapy as frequent causes of secondary HLH in adults.
Patient & Prescribing Data
A 41-year-old man with psoriasis treated with adalimumab, presenting with systemic illness and HLH associated with Histoplasma capsulatum.
Treatment described included dexamethasone 20 mg intravenously daily, ruxolitinib 10 mg twice daily, one rituximab dose of 375 mg/m², and liposomal amphotericin B; etoposide 150 mg/m² was planned but never given because of gastrointestinal hemorrhage.
Clinical Best Practices
The authors state that suspected HLH evaluation should account for immunosuppression and potential triggers, including invasive fungal infection in patients exposed to TNF-α inhibitors.
The article describes focused assessment and biopsy of clinically pertinent, newly developed or atypical lesions as a way to investigate an infectious source in immunosuppressed patients.
In this case, negative bone marrow fungal stains did not exclude infection identified by skin biopsy and molecular testing.
