INTRODUCTION: Aspergillus tracheobronchitis (ATB) is a rare manifestation of invasive aspergillosis. Various forms described include ulcerative, nodular-obstructing, and pseudomembranous. The ulcerative type is the least common and was first described in heart-lung and lung transplant patients. Ulcerative aspergillus involving the tracheobronchial tree has been described in AIDS patients. Nodular-obstructing and pseudomembranous tracheobronchitis have been described in lupus, diabetes, bone marrow transplant (BMT), and stem cell transplant (SCT) patients. We report the first case of ulcerative type in a SCT patient.
CASE PRESENTATION: A 54 year old woman diagnosed with myelodysplastic syndrome received matched sibling SCT 6 months prior to admission was admitted with a 3 day history of painful and pruritic rash involving limbs, face and back. She received treatment for graft versus host disease (GVHD), with methylprednisolone and tacrolimus. Stage II GVHD was confirmed with a skin biopsy. Micafungin was added for fungal prophylaxis. Physical showed macular hyperpigmented maculopapular rash. The Chest X-ray (CXR) was normal, and laboratory evaluation revealed elevated liver enzymes, thrombocytopenia and anemia without neutropenia.One week into the hospital stay, patient developed cough, and CXR and CT demonstrated a new left lower lobe (LLL) consolidation and a right upper lobe nodular density. Patient was started on broad-spectrum antibiotics for bacterial pneumonia and Voriconazole for presumed invasive aspergillus. After platelet transfusion she underwent bronchoscopy with intent to biopsy the LLL. Bronchoscopy revealed multiple shallow approximately 0.5 cm ulcers throughout the tracheobronchial tree. Ulcers had a dusky appearance, with shallow base and raised edges; with no evidence of pseudomembrane or nodules or increased respiratory secretions. Multiple biopsies for histopathology and cultures were obtained from the tracheal ulcers and LLL. Differential diagnosis included infectious etiology(viral, fungal, bacterial)GVHD, drug reaction. The histology of the LLL biopsies demonstrated poorly preserved fungal hyphae in the tissue, confirmed by special stains. The tracheal biopsies revealed detached fungal colonies suggestive of aspergillus as well as invasive fungal hyphae. BAL Cultures confirmed the presence of aspergillus species. The patient was continued on voriconazole and discharged without complications.
DISCUSSIONS: All cases of ATB in SCT/BMT patients reported in literature were of the pseudomembranous or nodular-obstructing variety, which were uniformly fatal. This is the first case to our knowledge, of an ulcerative variety of ATB in a SCT patient. It is unclear if the various forms of tracheobronchitis represent a progression of the disease from the mild ulcerative to the fulminant pseudomembranous and nodular-obstructing or represent distinct varieties of invasive ATB. Our patient was on fungal prophylaxis with micafungin, which has activity against aspergillus and may have contributed to a benign course. Our patient's risk factor for invasive aspergillus may have been GVHD and corticosteroid use. Although, tracheobronchial involvement versus lung involvement remains obscure. In lung transplant patients, it is hypothesized that decreased muco-ciliary clearance leads to ulcerative ATB. This is evident in single lung transplant patients who have involvement of the transplanted lung. It is possible that the ulcerative variety, which does not seem to follow a fulminant course, may be a result of prompt recognition and treatment in lung transplant patients, where the bronchoscopy threshold is low, thus, preventing progression to the more fulminant forms. Though the ulcerative variety has been described in lung transplant and AIDS patients ours is the first where gross antemortem pictures have been obtained for review.
CONCLUSION: In conclusion, our patient had a benign course because of early recognition and prompt treatment and perhaps, prophylactic micafungin therapy. ATB, though rare, is a potentially serious or fatal complication in SCT and GVHD. However early recognition and treatment maybe life saving. The optimal duration of treatment is unknown, but a prolonged course may be warranted to prevent relapse.
DISCLOSURE: Ajit Moghekar, None.