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Chronic granulomatous disease with pulmonary mass-like opacities secondary to hypersensitivity pneumonitis: a case report
© Katsuya et al.; licensee BioMed Central Ltd. 2014
Received: 5 April 2014
Accepted: 27 May 2014
Published: 2 July 2014
Chronic granulomatous disease, one of the primary immunodeficiency syndromes, is characterized by failure of phagocytic capacity due to loss of reactive oxygen species production, as well as formation of granulomas in organs. Clinically, dysregulated inflammation by excessive cytokine production due to loss of reactive oxygen species production is suggested as a cause of noninfectious inflammatory problems such as chronic granulomatous disease colitis. We experienced a rare case of a patient with chronic granulomatous disease with unique pathological and radiological presentations of hypersensitive pneumonitis, which to our knowledge has never been previously reported.
A 20-year-old Japanese man with chronic granulomatous disease was referred due to cough and abnormal chest imaging findings. Computed tomography of his chest showed diffuse, bilateral, centrilobular nodules and multiple mass lesions in lower lobes that do not fit a common image of hypersensitivity pneumonitis. Pathological findings of both nodules and mass lesions on surgical lung biopsy were homogeneous, and excessive granulomas in the bronchioles and alveolar duct as well as lymphocytic alveolitis were seen, all consistent with hypersensitivity pneumonitis. The radiological and laboratory abnormalities did not improve after antigen avoidance; however, they disappeared after high-dose steroid therapy.
When we encounter a case of hypersensitive pneumonitis showing atypical pulmonary mass-like opacities in a patient with chronic granulomatous disease, we should consider hyperinflammatory status and excessive granuloma formation of chronic granulomatous disease and start with high-dose steroid therapy as treatment.
Chronic granulomatous disease (CGD) is a hereditary immunodeficiency disease characterized by failure of phagocytic capacity due to a defect of nicotinamide adenine dinucleotide phosphate reactive oxygen species production and lack of bacterial killing, which causes recurrent life-threatening infections. The mechanism for granuloma formation remains unclear, but the neutrophilic response persists for an abnormally long period at sources of inflammation and results in chronic inflammation. However, reactive oxygen species also regulate cell signaling by activating nuclear factor-κB and other transcription factors and the production of cytokines such as interleukin-1β and tumor necrosis factor-α, even in nonphagocytic cells. Clinically, dysregulated inflammation by excessive cytokine production due to loss of reactive oxygen species production is suggested as a cause of noninfectious inflammatory problems such as CGD colitis[1, 2]. Here, we report unusual pathological and radiological presentations of hypersensitive pneumonitis in a patient with CGD, which have never been reported.
A 20-year-old Japanese man was referred due to nonproductive cough and abnormal findings on chest imaging. His mother was a heterozygous carrier of CGD, and he was diagnosed as having X-linked recessive CGD lacking gp91phox at the age of 1 year. He was given prophylaxis with trimethoprim-sulfamethoxazole and itraconazole and had been well for 19 years. When he was 19-years old, he developed CGD-related colitis and started treatment with prednisone 45mg per day. He started working at a warehouse 4 months later. After 3 months, a routine chest X-ray showed abnormalities. He then developed a nonproductive cough unresponsive to either antibiotics or antifungals.
Considering the negative findings for infectious disease, high-dose steroid therapy was started. The centrilobular nodules then disappeared, the mass lesions shrank, and his serum KL-6 decreased.
According to the analysis of 25 CGD surgical specimens, granulomas in patients with CGD were typically 100μm or less in diameter and contained central neutrophil microabcesses surrounded by a layer of palisading epithelioid histiocytes and giant cells. They spread not only in airways, but also in lung parenchyma. In the same specimens, Aspergillus species were isolated in 44% and bacterial organisms were cultured in 28%[3, 4].
In this case, the following three differential diagnoses of mass-like opacities were considered: CGD, fungal or bacterial infection, and hypersensitivity pneumonitis. First, the granulomas were loosely formed and relatively larger than those of CGD, they did not contain central microabcesses, and they spread through the airway to the lymph tract, consistent with hypersensitivity pneumonitis. Second, bacterial or fungal infection was proven neither histologically nor bacteriologically. Although no inhaled antigen was proven, his past history of working at a warehouse indicated that fungal exposure might have caused hypersensitivity pneumonitis.
Recent reports show an excessive release of inflammatory cytokines such as from neutrophils in patients with CGD. Animal models of CGD also show the hyperinflamed immune dysregulation seen in CGD, which explain excessive granuloma formation in organs such as the gastrointestinal system and the genitourinary system. Experiments performed in this case showed that the patient’s T cells in the bronchoalveolar lavage fluid produced excessive cytokines after incubation with or without antigen stimulation in vitro (data not shown). These findings lead to the possibility that excessive inflammation in T cells of patients with CGD explains atypical granuloma formation, such as the homogeneous and excessive amount of loose-formed granulomas through the airway spreading into the lymph tracts, despite the subacute clinical course.
When we encounter a case of hypersensitive pneumonitis showing atypical pulmonary mass-like opacities in a patient with CGD, we should consider hyperinflammatory status and excessive granuloma formation of CGD and start with high-dose steroid therapy as treatment.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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