Allergic bronchopulmonary aspergillosis: an Indian perspective

PURPOSE OF REVIEW: Allergic bronchopulmonary aspergillosis is an immunologically mediated lung disease that is caused by hypersensitivity to antigens of the genus Aspergillus. This review summarizes the clinical presentation, radiologic profile, lung functions and immunologic studies on allergic bronchopulmonary aspergillosis from India. Data regarding Aspergillus sensitization in asthmatics are presented. The association of allergic bronchopulmonary aspergillosis with allergic Aspergillus sinusitis and aspergilloma is also highlighted. RECENT FINDINGS: Allergic bronchopulmonary aspergillosis is now an emerging disease in India. Sensitization to Aspergillus antigens is not uncommon in our patients with asthma. Although asthma commenced in these subjects in their early 20s, allergic bronchopulmonary aspergillosis was recognized more than a decade later. Allergic bronchopulmonary aspergillosis can also occur in patients without clinical asthma. Radiology is crucial to the diagnosis of allergic bronchopulmonary aspergillosis. The remarkable radiological similarity to pulmonary tuberculosis has important clinical implications in our country as patients with allergic bronchopulmonary aspergillosis often receive antituberculous therapy for a long time. Although oral corticosteroids still remain the cornerstone for management, itraconazole has emerged as an adjunct therapy in appropriate situations. Concomitant occurrence of allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis is now being increasingly recognized. SUMMARY: All asthmatic subjects with a positive skin prick test to Aspergillus antigens must be evaluated for allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis should be excluded.     

Emerging and less common fungal pathogens

Less common and emerging fungal pathogens are often resistant to conventional antifungal therapy and may cause severe morbidity and mortality in immunocompromised hosts. Some Scedosporium species may be completely resistant to antifungal therapy. Hyaline septated filamentous fungi, such as Fusarium species, Acremonium species, Paecilomyces species, and Trichoderma species, are increasingly reported as causing invasive mycoses refractory to amphotericin B therapy. Dematiaceous septated filamentous fungi, such as Bipolaris species may cause pneumonia, sinusitis, and CNS infections that are unresponsive to current medical interventions. Trichosporon spp are resistant to the fungicidal effects of amphotericin B. An increasing number of different members of the class Zygomycetes are reported as causing lethal infections, despite aggressive medical and surgical interventions. Infections due to these and other less common and emergent fungal pathogens will likely continue to develop in the settings of selective anti-fungal pressure, permissive environmental conditions, and an expanding population of immunocompromised hosts.     

Report of successful prolonged antifungal therapy for refractory allergic fungal sinusitis.

Allergic fungal sinusitis (AFS) is an increasingly recognized cause of refractory chronic sinusitis in the young immunocompetent host, analogous to allergic bronchopulmonary aspergillosis (ABPA), a related process in the lower respiratory tract. Most patients experience remittent disease despite corticosteroid therapy and aggressive sinus surgery. Because controlled trials have shown adjunctive antifungal therapy to be of benefit in treating ABPA, long-term oral itraconazole was used in a young man with remittent AFS, which was able to break the cycle of relapsing disease.     

Case Report: Allergic Bronchopulmonary Aspergillosis and Allergic Fungal Sinusitis Successfully Treated with Voriconazole

Allergic bronchopulmonary aspergillosis and allergic fungal sinusitis are closely related disorders that rarely present in the same individual. The mainstay of treatment for allergic bronchopulmonary aspergillosis is systemic corticosteroids. Itraconazole is used as adjunctive therapy in refractory cases. Allergic fungal sinusitis requires initial sinus surgery followed by systemic steroids. Antifungal therapy has not proven to be beneficial in allergic fungal sinusitis. We report a case of concomitant allergic bronchopulmonary aspergillosis and allergic fungal sinusitis that was refractory to standard therapy but had dramatic clinical response following treatment with voriconazole.     

呼吸系统曲霉菌病重叠综合症的新进展

肺部曲霉菌病是少见病,但近年逐年增多,包括变应性支气管肺曲菌病(allergic bronchopulmonary aspergillosis,ABPA)、曲菌球(aspergilloma)、慢性坏死性肺曲菌病(chronic necrotizing aspergillosis,CNA)、侵袭性肺曲菌病(invasive pulmonary aspergillosis,IPA)及全身播散性曲菌病等5型.其中ABPA、曲菌球甚至IPA可合并变应性曲霉菌性鼻窦炎(allergic Aspergillus sinusitis,AAS),可能与基础病及其治疗等因素有关.本文就近期文献报告的呼吸系统曲霉菌病重叠综合症作一综述.     

Allergic bronchopulmonary disease caused by Bipolaris hawaiiensis presenting as a necrotizing pneumonia: case report and review of literature

We report a case of allergic bronchopulmonary disease caused by Bipolaris hawaiisensis in an immunocompetent host, presenting with symptoms and radiographic findings suggestive of necrotizing pneumonia. Cultures of the plugs and bronchial washing yielded the pathogenic fungi. Laboratory tests revealed eosinophilia and elevation of serum IgE. This patient was successfully treated with steroids, amphotericin B lipid complex, and itraconazole. Review of 10 previously reported cases and their clinical manifestations and treatment are presented.     

Fungal rhinosinusitis: Diagnosis and therapy

Fungal rhinosinusitis presents in five clinicopathologic forms, each with distinct diagnostic criteria, treatment, and prognosis. The invasive forms are acute fulminant, chronic, and granulomatous ("indolent") invasive fungal sinusitis. The noninvasive forms are fungal ball ("sinus mycetoma") and allergic fungal sinusitis (AFS). AFS is the most common form of fungal rhinosinusitis. Patients with AFS are atopic to aeroallergens including the involved fungal organism, immunocompetent, have nasal polyps and chronic allergic rhinosinusitis, often produce nasal casts, and may occasionally present with proptosis from orbital extension of disease. Sinus CT shows sinus mucosal hypertrophy and often hyperattenuation of sinus contents. Diagnosis is made from surgical histopathology with or without an associated positive surgical sinus fungal culture. The histopathology shows extramucosal allergic mucin that stains positive for scattered fungal hyphae and eosinophilic-lymphocytic sinus mucosal inflammation. Bipolaris spicifera is the most common fungus cultured. The immunopathology of AFS has been shown to be analogous to allergic bronchopulmonary aspergillosis. Treatment requires surgery and aggressive postoperative medical management with close follow-up. Medical treatment includes allergy medications, allergen immunotherapy, and in many cases the addition of oral corticosteroids. Although medical management clearly improves patient outcomes, more studies are needed because AFS recurrence rates remain high.     

Allergic fungal sinusitis presenting as a paranasal sinus tumor

We present a case of allergic fungal sinusitis (AFB) in a 20-year old man with few months' history of bilateral nasal obstruction and discharge with unilateral proptosis that underwent maxillary antrostomy due to the mass in paranasal sinuses. Histological examination of tissue showed branching fungal hyphae interspersed with allergic mucin without fungal invasion to soft tissue. The patient received local steroid for 4 months and had no problem during follow up. Fungal culture was performed and Bipolaris fungus grew. Although most dematiaceous fungal infections occur in immunocompetent patients, the incorrect diagnosis and insufficient treatment may be life threatening.     

Cunninghamella infection post bone marrow transplant: case report and review of the literature

Cunninghamella spp., in the class Zygomycete and order Mucorales, are unusual opportunistic pathogens that have been identified with increased frequency in immunocompromised patients. Infections with this group of organisms have been seen most frequently in patients with hematologic malignancy. We describe an allogeneic bone marrow recipient who developed fungal pneumonitis and disseminated fungal dermatitis caused by Cunninghamella spp. To our knowledge, this is the first reported case of Cunninghamella infection in a BMT recipient. The case highlights the mortality associated with opportunistic infections in immunocompromised patients and confirms the risk factors associated with non-candida fungal infections after bone marrow transplantation.     

Allergic fungal sinusitis presenting with proptosis and diplopia: a review of ophthalmologic complications and treatment.

Allergic fungal sinusitis is a noninvasive, but vigorous, inflammatory response to mold that occurs in immunocompetent patients with chronic sinusitis and nasal polyposis. It typically occurs in patients who have a history of atopic disease. Occasionally, the patients with allergic fungal sinusitis present with ophthalmic signs and symptoms--most commonly proptosis and diplopia. We report the case of a 23-year-old man with right-sided proptosis, diplopia, and nasal obstruction. He had a history of sinusitis in the past. On presentation, sinus computed tomography scan showed pansinusitis. Subsequent workup revealed elevated immunoglobulin E and positive skin testing to several molds including Bipolaris spicifera and Aspergillus fumigatus. Functional endoscopic sinus surgery was performed, and the surgical specimen revealed allergic mucin with eosinophils, Charcot-Leyden crystals, and a silver stain showing fungal elements. His symptoms, including proptosis and diplopia, improved after surgical debulking and use of systemic corticosteroids.     

Dematiaceous fungi

Dematiaceous fungi are the etiologic agents of phaeohyphomycosis and are increasingly recognized as causing disease in humans. A wide variety of infectious syndromes are seen, from local infections due to trauma to widely disseminated infection in immunocompromised patients. Pulmonary disease may be divided into allergic bronchopulmonary and nonallergic syndromes, depending on the species. These fungi have unique pathogenic mechanisms owing to the presence of melanin in their cell walls, which imparts the characteristic dark color to their spores and hyphae. Melanin is a known virulence factor in certain fungi, including Cryptococcus neoformans and Wangiella dermatitidis. Therapy depends upon the clinical syndrome. Local infection may be cured with excision alone, whereas systemic disease is often refractory to therapy. Azoles such as itraconazole and voriconazole have the most consistent in vitro activity, though there is more clinical experience with itraconazole. Further studies are needed to better understand the pathogenesis and treatment of these uncommon infections.     

Invasive and Allergic Fungal Sinusitis

Fungal sinusitis encompasses a wide range of clinical syndromes. Disease is classified into four major categories: 1) acute invasive fungal sinusitis, 2) chronic invasive fungal sinusitis, 3) mycetoma, and 4) allergic fungal sinusitis. Acute disease is most often a fulminant, life-threatening process seen in immunocompromised patients. Treatment requires prompt antifungal therapy and extensive surgical debridement. Other types of fungal sinusitis are more indolent. For chronic invasive sinusitis, a combination of surgical debridement and antifungal agents is the cornerstone of treatment. Mycetomas can usually be extirpated surgically and do not require therapy with antifungal agents. Treatment of allergic fungal sinusitis remains controversial, but most current management regimens utilize surgical debridement combined with corticosteroid therapy, rather than antifungal agents.     

ALLERGIC FUNGAL SINUSITIS PRESENTING AS A PARANASAL SINUS TUMOUR

Allergic fungal rhinosinusitis is a rare complication of atopic upper airways disease which may present initially as an expansive tumour of the paranasal sinuses. This reported case was caused by the rare fungal pathogen Bipolaris hawiiensis and illustrates typical clinical and laboratory features of this disorder. Although the optimum management of allergic fungal sinusitis is controversial, combined therapy with surgical clearance, antifungal agents and corticosteroids produced a favourable outcome.     

New spectrum of fungal infections in patients with cancer

We report on 44 cancer patients who had serious infections with unusual fungal pathogens and who were cared for at our cancer center between 1974 and 1986. Twelve different fungal species accounted for these infections, including Trichosporon beigelii, Fusarium species, Geotrichum candidum, Curvularia species, Drechslera species, Penicillium species (but not Penicillium marneffei), Rhodotorula rubra, Pseudallescheria boydii, Pichia farinosa, Torulopsis pintolopesii, Saccharomyces cerevisiae, and Cunninghamella bertholletiae. Skin lesions were noted in seven patients, and sinusitis occurred in four. Twenty-four patients had disseminated infection, 12 had involvement of a single organ, and eight had fungemia alone. Features that correlated with a poor prognosis were persistent neutropenia and disseminated visceral infection but not fungemia alone. We suggest that unusual fungi have now emerged as significant pathogens in this patient population. Fungal sinusitis, previously caused by Aspergillus species and the phycomycetes, also occurs as a result of some of these newly recognized fungi. A high level of suspicion should be maintained when any of these unusual fungi are cultured from clinical specimens from immunocompromised patients.     

The assessment of immunologic and clinical changes occurring during corticosteroid therapy for allergic bronchopulmonary aspergillosis

Twenty-two patients with allergic bronchopulmonary aspergillosis have been treated and evaluated for a period ranging from two months to nine years. Twelve are available for periodic blood sampling. Data are presented suggesting the following: (1) Patients with allergic bronchopulmonary aspergillosis have high initial levels of total serum immunoglobulin E (IgE). These levels are significantly higher in those patients who had not been previously treated with prednisone for the control of asthma. (2) Treatment with alternate day prednisone (0.5 mg/kg given on alternate days) caused clinical and roentgenologic improvement as well as marked decreases in total serum IgE but does not necessarily prevent recurrence of the disease. (3) Total and specific IgE against Aspergillus antigen may increase prior to and during exacerbations of disease. (4) Specific IgG and IgE against Aspergillus antigen are increased in most patients with allergic bronchopulmonary aspergillosis and reflect disease activity as evidenced by x-ray and clinical exacerbations in some cases. (5) Lymphocyte transformation using Aspergillis antigen, as measured by the whole blood technic, is present in patients with allergic bronchopulmonary aspergillosis, but serial changes in lymphocyte transformation do not correlate with disease activity. (6) Precipitin reactions are present in patients with allergic bronchopulmonary aspergillosis, but presence or absence does not reflect disease activity in most cases.     

Sinusitis and asthma: Associated airway diseases

Sinusitis and asthma often coexist in patients. In fact, these airways disorders are similar histologically, with tissue eosinophils, increased glandular tissue, and edema. Medical or surgical therapy for sinusitis often greatly improves asthma, suggesting that sinusitis may exacerbate asthma. Possible mechanisms by which asthma could be worsened by sinus disease include neural reflex pathways and interference with the important nasal functions of heating, humidification, and filtration. Health professionals treating asthmatic patients should consider sinusitis as a possible underlying cause, in addition to other triggers (eg, allergic rhinitis and gastroesophageal reflux disease).     

Nocardiosis: a review.

Infections caused by Nocardia species are infrequent but challenging to clinicians. They cause a wide variety of diseases in both normal and immunocompromised patients. In recent years, the number of case reports has been increasing, and this can be attributed to the improvements in diagnostic capabilities and the higher clinical index of suspicion accompanying the increased prevalence of immunosuppressed patients. The treatment of nocardiosis also requires expertise. This report reviews the epidemiology, physiopathology, clinical manifestations, diagnosis and treatment of this aerobic bacterial disease.     

The spectrum of CFTR-related disease.

There is increasing appreciation for the presence of diseases which do not fit the criteria for classic cystic fibrosis but are caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR). This case describes a patient with documented CFTR dysfunction by nasal potential difference measurement who presents with chronic idiopathic pancreatitis, sinusitis, and allergic bronchopulmonary aspergillosis (ABPA), but not congenital bilateral absence of the vas deferens (CBAVD) or other classic symptoms of cystic fibrosis. This rare case demonstrates both the spectrum of disease which can be seen with CFTR dysfunction and the steps required to document CFTR involvement.     

Nontuberculous mycobacterial infections of the lung

There is an increasing appreciation for the role of nontuberculous mycobacteria (NTM) as pathogens causing pulmonary disease, disseminated disease, or both in immunocompetent and immunocompromised individuals. Species previously considered nonpathogenic have been shown to cause pulmonary infection. The majority of immunocompetent patients with NTM pulmonary infection have underlying lung disease. New diagnostic techniques such as gene probes, gas-liquid and high-pressure chromatography, and polymerase chain reaction offer significant advantages in the rapid identification of NTM species. Some of these techniques allow identification of mycobacteria directly from clinical specimens. The fluoroquinolones, rifabutin, and newer macrolides offer advances in the treatment of infections that are caused by NTM and are resistant to the traditional antimycobacterial drugs.     

Aspergillosis and lung defenses

Aspergillosis refers to any of the illnesses caused by fungi that are members of the genus Aspergillus. The diseases range from allergic responses that occur in the absence of fungal growth (asthma, hypersensitivity pneumonitis), to colonization with or without an allergic component (allergic bronchopulmonary aspergillosis, aspergilloma, saprophytic involvement of infarcted tissue), to invasion and destruction of lung parenchyma (invasive aspergillosis, chronic necrotizing pulmonary aspergillosis). The development of lung infection and/or disease depends on interaction among three factors: the characteristics of the fungus (virulence factors), the status of host defense mechanisms, and the type of exposure. The purpose of this article is to review these factors and their relationship to the clinical syndromes of aspergillosis.