INTRODUCTION: Invasive aspergillosis is a severe infection that usually affects immunocompromised patients. We report a case of invasive pulmonary aspergillosis in a young, otherwise seemingly healthy woman.
CASE PRESENTATION: A 35 year old woman with mild intermittent asthma presented with a 3 day history of fever to 103.7°F, non-productive cough and dyspnea. There was no sore throat, rash,arthralgia or diarrhea. She is an avid runner and lifetime nonsmoker. She enjoys gardening and recently deposited some cut grass in a nearby compost. There was no recent travel and her only medication was an albuterol inhaler.Her physical examination was remarkable for bilateral crackles at the bases.CXR revealed diffuse reticulonodular infiltrates (see figure 1) and CBC was significant for 7% eosinophils (see table2 initial presentation). She was given an outpatient course of azithromycin.Without improvement, she returned 3 days later with persistent fever and dyspnea. Her oxygen saturation on room air was 86% prompting hospital admission. Bronchoscopy with bronchoalveolar lavage (BAL) revealed 69% eosinophils. Bacterial, viral and mycobacterial cultures were negative (table 1st admission). Workup for autoimmune disease and stool for ova and parasites were negative. Her IgE level was elevated at 2440 (table 1st admission). A diagnosis of acute eosinophilic pneumonia was made and systemic corticosteroids were started with remarkable clinical and radiological improvement. She was discharged on a prednisone taper and TMP-SMX for pneumocystis jiroveci pneumonia prophylaxis (PJP). The patient returned 5 days later with worsening dyspnea and recurrent fever. Her PaO2 was 66 mmHg on room air and CXR revealed worsening bilateral infiltrates. She was admitted to the intensive care unit. Bronchoscopy was repeated and transbronchial biopsy revealed evidence of hyphae branching at 45° angle with possible vasculitis. Video assisted thoracoscopic surgery with lung biopsy, fungal stain and culture confirmed the presence of invasive aspergillosis without vasculitis. Immunoglobulin subclasses, HIV and screening for cystic fibrosis were negative. Nitroblue tetrazolium test was positive. Genetic testing confirmed the presence of autosomal recessive chronic granulomatous disease (CGD). Final diagnosis: fulminant invasive pulmonary aspergillosis and autosomal recessive CGD. Antifungals, gamma interferon and systemic steroids were started and after a prolonged hospital course, she was discharged to a rehabilitation facility where she completed her recovery and returned home. CXR revealed remarkable resolution of the infiltrates.
DISCUSSIONS: CGD is a rare group of inherited diseases with annual incidence of 1/255,000 live births and characterized by recurrent infections with catalase positive microorganisms including many bacteria and fungi. The gene mutation in the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme complex renders the leukocyte unable to kill the ingested microorganisms. The X-linked form of the disease (gp91phox) is more common and carries a worse prognosis. It affects females more often and manifests with recurrent infections early in life. The autosomal recessive form (P22phox, P47phox, and P67phox) is less common,affects males more than females and carries a better prognosis. Patients with this form may present with infections in late adulthood. Pulmonary disease is most common however, cellulitis, osteomyelitis and abscesses were reported. Mortality rate is 17.6% and pneumonia due to aspergillus or Burkholderia cepacia is the most common cause of death. Prophylaxis with TMP-SMX and interferon gamma was shown to reduce the rate of infections. Systemic corticosteroids were reported to be beneficial in reducing the exuberant inflammatory response in life threatening infections.
CONCLUSION: CGD is rare inherited disease characterized by increased susceptibility to recurrent infections. Acute invasive aspergillosis in the absence of known immunodeficiency should prompt consideration of CGD.
DISCLOSURE: Ghazwan Acash, No Financial Disclosure Information; No Product/Research Disclosure Information