Recurrent hemoptysis with Penicillium marneffei and Stenotrophomonas maltophilia in Job ’ s syndrome

1Department of Surgery; 2Department of Microbiology; Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China Correspondence: Dr Calvin SH Ng, Division of Cardiothoracic Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China. Telephone 852-2632-2629, fax 852-2637-7974, e-mail calvinng@surgery.cuhk.edu.hk Case presentation A 30-year-old man was admitted to hospital for the management of massive hemoptysis. He had a long history of childhood cutaneous infections and recurrent pneumonia complicated by empyema, and thoracic and pulmonary abscesses that required prolonged intravenous antibiotics and surgical decortications. His family history was unremarkable. A previous sweat test was negative. Further investigations revealed marked eosinophilia and grossly elevated serum immunoglobulin (Ig) E levels of 2510 IU/L (normal range 0 to 100 IU/L), but normal IgA, IgG and IgM levels, which led to the clinical diagnosis of Job’s syndrome. Despite prophylactic oral antibiotics (predominantly ampicillin-based), he suffered from further bouts of severe pneumonia with massive hemoptysis and the subsequent development of a large right upper lobe cavitating abscess that required lobectomy. Interestingly, the abscess culture grew Stenotrophomonas maltophilia, which was successfully treated with sulperazone (cefoperazone and sodium sulbactam). During the current admission 10 years later, he again presented with dyspnea and life-threatening hemoptysis. Multiple scars were noted from previous skin abscesses of the face and limbs, as well as from bilateral thoracotomy incisions. Breath sounds were reduced bilaterally, especially over the right side. A complete blood panel revealed leukocytosis (white blood cell count 16.4×109/L [normal range 4×109/L to 11×109/L]), predominantly neutrophils (85.1%) and eosinophils (9.5%). A chest radiograph showed consolidative changes and cavitations over the right lower zone. Computed tomography revealed multiple pneumatoceles (Figure 1), the largest being 5.5 cm in size, with fluid levels in the right lower lobe. Urgent angiography was performed and two culprit hypertrophic bronchial arteries supplying the right main and right lower lobe bronchi (Figure 2A) were successfully occluded by microsphere embolization (500 μm to 700 μm) (Figure 2B), with subsequent resolution of hemoptysis. In addition, percutaneous drainage of the dominant lung abscess was performed. Both sputum and abscess fluid cultures grew Penicillium marneffei, which produces a characteristic soluble red pigment at 30°C (Figure 3). The patient was treated with amphotericin B and the prophylactic antibiotic cefepime. Despite appropriate antifungal and antibiotic therapy, his contralateral lung also rapidly became infected and he finally succumbed to respiratory failure.


Case presentation
A 30-year-old man was admitted to hospital for the management of massive hemoptysis.He had a long history of childhood cutaneous infections and recurrent pneumonia complicated by empyema, and thoracic and pulmonary abscesses that required prolonged intravenous antibiotics and surgical decortications.His family history was unremarkable.A previous sweat test was negative.Further investigations revealed marked eosinophilia and grossly elevated serum immunoglobulin (Ig) E levels of 2510 IU/L (normal range 0 to 100 IU/L), but normal IgA, IgG and IgM levels, which led to the clinical diagnosis of Job's syndrome.Despite prophylactic oral antibiotics (predominantly ampicillin-based), he suffered from further bouts of severe pneumonia with massive hemoptysis and the subsequent development of a large right upper lobe cavitating abscess that required lobectomy.Interestingly, the abscess culture grew Stenotrophomonas maltophilia, which was successfully treated with sulperazone (cefoperazone and sodium sulbactam).
During the current admission 10 years later, he again presented with dyspnea and life-threatening hemoptysis.Multiple scars were noted from previous skin abscesses of the face and limbs, as well as from bilateral thoracotomy incisions.Breath sounds were reduced bilaterally, especially over the right side.A complete blood panel revealed leukocytosis (white blood cell count 16.4×10 9 /L [normal range 4×10 9 /L to 11×10 9 /L]), predominantly neutrophils (85.1%) and eosinophils (9.5%).A chest radiograph showed consolidative changes and cavitations over the right lower zone.Computed tomography revealed multiple pneumatoceles (Figure 1), the largest being 5.5 cm in size, with fluid levels in the right lower lobe.Urgent angiography was performed and two culprit hypertrophic bronchial arteries supplying the right main and right lower lobe bronchi (Figure 2A) were successfully occluded by microsphere embolization (500 µm to 700 µm) (Figure 2B), with subsequent resolution of hemoptysis.In addition, percutaneous drainage of the dominant lung abscess was performed.Both sputum and abscess fluid cultures grew Penicillium marneffei, which produces a characteristic soluble red pigment at 30°C (Figure 3).The patient was treated with amphotericin B and the prophylactic antibiotic cefepime.Despite appropriate antifungal and antibiotic therapy, his contralateral lung also rapidly became infected and he finally succumbed to respiratory failure.

DisCussion
The term Job's syndrome was coined in 1966 by Davis et al (1), who described a rare condition characterized by recurrent staphylococcal skin infections, sinusitis, otitis media and pulmonary infections.Other clinical manifestations described since then include candida endocarditis, keratitis and corneal perforation, craniofacial and dental abnormalities, and skeletal deformities (2).Pulmonary complications such as recurrent pneumonia, pneumatocele formation and lung abscesses caused by bacterial and fungal infections are also common (3-7) (Table 1).
The mode of inheritance appears to be autosomal dominant with incomplete penetrance, although most cases are sporadic in nature (2,8,9) Pulmonary infection caused by the opportunistic organisms Penicillium marneffei and Stenotrophomonas maltophilia in patients with Job's syndrome is rare and not well documented.The case of a 30-year-old man with Job's syndrome who developed recurrent pneumonia and lung abscesses caused by P marneffei and S maltophilia, complicated by massive hemoptysis, is described.Bronchial artery embolization was successful in controlling the hemoptysis; however, the infection proved fatal despite appropriate antimicrobial therapy.A brief review of the literature on Job's syndrome and its associated infective pulmonary manifestations is also presented.

Hémoptysie récurrente avec Penicillium marneffei et Stenotrophomonas maltophilia dans le syndrome de Job
L'infection pulmonaire opportuniste causée par Penicillium marneffei et Stenotrophomonas maltophilia chez des patients atteints du syndrome de Job est rare et peu documentée.Les auteurs décrivent ici le cas d'un homme de 30 ans atteint du syndrome de Job ayant présenté une pneumonie et des abcès pulmonaires récurrents à P. marneffei et S. maltophilia, compliqués par une hémoptysie massive.L'embolisation de l'artère bronchique a été réalisée avec succès et a permis de maîtriser l'hémoptysie.Toutefois, l'infection s'est révélée fatale malgré l'administration d'une antibiothérapie appropriée.Les auteurs présentent en outre une brève revue de la littérature sur le syndrome de Job et les manifestations infectieuses pulmonaires qui y sont associées.8).Interferongamma, a lymphokine that enhances neutrophil respiratory burst and bactericidal activity, has also been found to be at significantly lower levels or undetectable in patients with Job's syndrome.Recombinant human interferon-gamma was demonstrated to enhance neutrophil chemotactic response in Job's syndrome (10).Furthermore, antihistamines (ie, H 2 receptor antagonists) such as cimetidine, have been suggested   as another possible treatment to enhance neutrophil chemotactic ability (11).Pulmonary pathogens that have been commonly associated with Job's syndrome include Staphylococcus, Pseudomonas, Aspergillosis and Candida species (Table 1).Of interest, our patient's lung abscesses were caused by the atypical organisms P marneffei and S maltophilia.The associations of these two organisms with Job's syndrome have not been well documented in the English literature.P marneffei was discovered in 1956 as a naturally occurring sylvatic fungus within numerous bamboo rat species endemic to southeast Asia and southern China.It commonly causes respiratory, cutaneous and systemic infections in immunocompromised patients, especially those with AIDS or receiving renal and bone marrow transplantation (12).In contrast, S maltophilia is an aerobic Gram-negative bacillus and an infrequent pathogen in humans.It is known to be a frequent colonizer in the hospital setting, in irrigation solution and in intravenous fluids.The organism is also associated with respiratory tract infection in immunocompromised patients, particularly those with cystic fibrosis (13).S maltophilia is usually resistant to multiple anti-microbial agents -the most effective agents are cefepime and trimethoprim with sulfamethoxazole.In our case, both amphotericin B and cefepime were administered to account for both organisms.

Recurrent hemoptysis in
The other challenge is the management of severe hemoptysis in the immunocompromised patient.Bronchial artery embolization (BAE) is quickly becoming a popular, less invasive approach for the treatment of hemoptysis.However, its clinical efficacy for infective causes of hemoptysis in immunocompromised patients, such as Job's syndrome, is not well documented.Only one other case of a successful BAE for massive hemoptysis from pneumonia and bronchial artery pseudoaneurysm (in a 2-year-old girl with Job's syndrome) is reported in the English literature (7).In the past, lung resections in Job's syndrome were reserved for uncontrolled pneumonia and pulmonary abscess rather than hemoptysis (3-7) (Table 1).One should also consider that the risk of postoperative infective complications and bronchopleural fistula would be significantly higher in the immunocompromised patient.BAE remains the initial treatment of choice for this select group of patients presenting with hemoptysis.
Job's syndrome Can Respir J Vol 16 No 4 July/August 2009 e51 dysfunction are thought to be the underlying deficiencies in Job's syndrome.Raised serum IgE levels and eosinophilia, which are diagnostic of Job's syndrome, are in fact not the principal cause because IgE production involves T cell stimulation and the ability of B cells to class switch into IgE production.The humoral immune system is dependent on cell-mediated immunity.Individuals with humoral immunodeficiency are prone to recurrent infections by pyogenic agents, especially encapsulated bacteria, such as Haemophilus influenzae, Streptococcus pneumoniae and staphylococci (

Figure 1 )Figure 2 )a
Figure 1) Computed tomography scan revealing multiple pneumatoceles with fluid level.The largest one is 5.5 cm in size (in the right lower lobe)

Figure 3 )
Figure3) Sputum culture at 30°C produced a mold.Identification was aided by the formation of a soluble red pigment that diffused into the agar

Table 1 Summary of the literature of pulmonary involvement in patients with Job's syndrome Pulmonary involvements Treatment and outcome Patient age, years/sex author (reference)
Right lower lobe pneumonia and life-threatening hemoptysisEmbolization with polyvinyl ethanol Pulmonary angiogram: Pseudoaneurysm from a hypertrophic bronchial artery