Specific antibodies to recombinant allergens of Aspergillus fumigatus in cystic fibrosis patients with ABPA

Background

Aspergillus fumigatus, a widely distributed fungus, has been implicated in causing life threatening infections as well as severe asthma and allergic diseases in man. Allergic affliction like allergic bronchopulmonary aspergillosis (ABPA) is a disabling lung disease frequently seen in patients with asthma and cystic fibrosis. Immunodiagnosis of the former is comparatively easier due to the availability of purified antigens and sensitive methods. However, this is not true with cystic fibrosis patients where the prevalence of ABPA is fairly high and the morbidity and mortality are significant.

Methods

In the present study, we have evaluated purified recombinant allergens from A. fumigatus, namely Asp f 1, f 2, f 3, f 4, and f 6 using ELISA and a semi-automated method (ImmunoCAP). We studied 17 patients each from cystic fibrosis with ABPA, and cystic fibrosis with asthma, 22 cystic fibrosis with no ABPA or asthma, and 11 age matched controls.

Results

The results indicate that no antigen, antibody or method is capable of differentiating cystic fibrosis (CF) with ABPA from other CF patients, although some allergens showed strong reaction or showed more prevalence among the patients studied.

Conclusion

When results of several allergens such as Asp f 1, f 2, f 3, f 4, and f 6 in their binding to IgA, IgG, and IgE antibodies were analyzed, a more strong discrimination of CF patients with ABPA was possible from the other groups studied.     

Allergic bronchopulmonary aspergillosis (ABPA): Studies on the general and specific humoral response

Serum specimens from 138 patients suffering from chronic respiratory disorders including 63 with allergic bronchopulmonary aspergillosis (ABPA), 20 with suspected ABPA, 25 with pulmonary tuberculosis, 14 with bronchial asthma, 10 with chronic bronchitis and 6 with miscellaneous pulmonary conditions were studied for circulating antibodies to Aspergillus. The ammonium sulfate test was employed with an iodine-125 labeled mycelial component derived from Aspergillus fumigatus. When compared to normal controls from the same area, this test indicated that sera from 82 per cent of patients with ABPA had elevated binding titers to the radiolabeled antigenic component. Immunodiffusion using a culture filtrate antigen from A. fumigatus, revealed precipitating antibody to this fungus in 89 per cent of sera from ABPA patients. The majority of patients with ABPA demonstrated marked elevations of total serum IgE, moderate elevations of serum IgA and IgD and slightly increased levels of IgG and IgM.This study was supported in part by Research Grant AI 10940 from the National Institutes of Health and by NHLI Contract N01-HL-3-2942(B), and forms a part of the Ph.D. thesis submitted by Z.U.K. to the University of Delhi.     

Immunoreactivity of antigen extracts of Aspergillus fumigatus isolated from different sources

Allergic bronchopulmonary aspergillosis (ABPA) is the result of hypersensitivity to Aspergillus antigens in patients with long-standing atopic asthma. In the present study mycelial and culture filtrate antigens from Aspergillus fumigatus cultures isolated from diverse sources were tested against sera of 10 ABPA patients and 10 control individuals by an ELISA methodology. The results indicate higher antibody reactivity against both antigens in the sera of ABPA patients, while culture filtrate antigens also gave non-specific reactivity with control sera. Mycelial extracts, in general, were useful in the diagnosis of ABPA.     

变应性支气管肺曲霉病的CT表现——附17例分析

目的探讨变应性支气管肺曲霉病(ABPA)的CT特点,进一步提高对该病的认识。方法回顾性分析17例AB-PA的CT表现,所有的患者均按目前的ABPA诊断标准进行诊断。结果 17例患者均有中心性支气管扩张征象,13例并支气管黏液栓形成,为分支状或挤牙膏状或长管状"Y"形,7例以树芽征为主要表现的小叶中心结节形成,9例有斑片状浸润影,2例随访见中心性支气管扩张有游走性。结论变应性支气管肺曲霉病(ABPA)的CT表现相对有特征性,以中心性支气管扩张为主,常伴有较高密度的支气管腔内黏液栓形成,结合临床一般能做出诊断。     

Occurrence of Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutations in Patients with Allergic Bronchopulmonary Aspergillosis Complicating Asthma

Background

Whether cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations contribute to the high prevalence of allergic bronchopulmonary aspergillosis (ABPA) in India remains unknown. We aimed to evaluate the occurrence of CFTR mutations in subjects with ABPA complicating asthma.

Methods

We sequenced the CFTR gene using genomic DNA from blood on the Illumina NextSeq500 platform. Before undertaking zygosity analysis by genome analysis toolkit, the known or novel single nucleotide polymorphisms (SNPs) and indels were called. For rigorous analysis, we included only high-quality SNPs (scores?>?500) and coverage ranging from 30 × 150x.

Results

We included 18, 12, and eight adult participants of ABPA, asthma, and healthy controls, respectively. The frequency of SNPs was higher in asthmatic subjects than ABPA or healthy controls, albeit not statistically significant (9/12 [75%] vs. 11/18 [61.1%] vs. 3/8 [37.5%], p?=?0.24). Of the 38 subjects, 23 yielded 50 variants (healthy controls [n?=?5], ABPA [n?=?22], asthma [n?=?23]) corresponding to six SNPs not previously linked with ABPA. Of these, four SNPs (rs213950, rs200735475, rs1800113, and rs1800136) were catalogued in the NCBI database. We identified two novel SNPs (chr7:117250703, chr7:117282655) in four (ABPA [n?=?1], asthma [n?=?3]) subjects without corresponding reference SNP. Most SNPs (85.5%) were heterozygous. The frequency of SNPs was higher in ABPA subjects with high-attenuation mucus (52.2%) and bronchiectasis (39.1%) than serological ABPA (8.7%).

Conclusions

Our study suggests the role of CFTR mutations in the pathogenesis of ABPA. The SNPs in the CFTR gene may contribute to disease severity in ABPA. Larger studies are required to confirm our findings.

     

HLA‐DRB1 and HLA–DQB1 genes on susceptibility to and protection from allergic bronchopulmonary aspergillosis in patients with cystic fibrosis

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity pulmonary disease that affects both patients with cystic fibrosis (CF) and those with asthma. HLA‐DRB1 alleles have previously been associated with ABPA–CF susceptibility; however, HLA‐DQB1 allele associations have not been clearly established. The aim of the present study was to investigate HLA class II associations in patients with ABPA–CF and determine their roles in susceptibility or protection. Patients with ABPA–CF, patients with CF without ABPA, patients with asthma without ABPA (AST), and healthy controls were included in this study. DNA was extracted by automatic extractor. HLA‐DRB1 and ‐DQB1 genotyping was performed by the Luminex PCR‐SSOP method (One Lambda, Canoga Park, CA, USA). Allele specific PCR‐SSP was also performed by high‐resolution analysis (One Lambda). Statistical analysis was performed with SSPS and Arlequin software. Both HLA‐DRB1*5:01 and ‐DRB1*11:04 alleles occurred with greater frequency in patients with ABPA–CF than in those with AST and CF and control subjects, corroborating previously published data. On the other hand, analysis of haplotypes revealed that almost all patients with ABPA–CF lacking DRB1*15:01 or DRB1*11:04 carry either DRB1*04, DRB1*11:01, or DRB1*07:01 alleles. In the HLA‐DQB1 region, the HLA‐DQB1*06:02 allele occurred more frequently in patients with ABPA–CF than in those with AST and CF and healthy controls, whereas HLA‐DQB1*02:01 occurred less frequently in patients with ABPA–CF. These data confirm that there is a correlation between HLA‐DRB1*15:01, –DRB1*11:04, DRB1*11:01, –DRB1*04 and –DRB1 * 07:01 alleles and ABPA–CF susceptibility and suggest that HLA‐DQB1*02:01 is an ABPA–CF resistance allele.     

Emotionally Triggered Asthma: A Review of Research Literature and Some Hypotheses for Self-Regulation Therapies

Asthma is a common disease whose morbidity and mortality are rapidly increasing. Panic disorder is common in asthma. Panic, other negative emotions, and a passive coping orientation may affect asthma by producing hyperventilation, increased general autonomic lability, a specific pattern of autonomic arousal that may cause bronchoconstriction, and/or detrimental effects on health care behaviors. Generalized panic is a risk factor for increased asthma morbidity. A repressive coping style also appears to be a risk factor for asthma morbidity because it is accompanied by an impaired ability to perceive symptoms, a necessary prerequisite for taking appropriate remediation. Several self-regulation strategies are hypothesized to be useful adjuncts to asthma treatment. Preliminary research has been done on relaxation therapy, EMG biofeedback, biofeedback for improved sensitivity in perceiving respiratory sensations, and biofeedback training for increasing respiratory sinus arrhythmia. It is hypothesized that finger temperature biofeedback also may be a promising treatment method, and that relaxation-oriented methods will have their greatest effect among asthmatics who experience panic symptoms, while improved perceptual sensitivity will be helpful both for patients who panic and those with repressive coping styles.     

Multi-symptom asthma is closely related to nasal blockage,rhinorrhea and symptoms of chronic rhinosinusitis-evidence from the West Sweden Asthma Study

Background

We have previously shown that approximately 25% of those with asthma in West Sweden have multiple asthma symptoms, which may describe a group of patients with more severe disease. Furthermore, asthma is associated with several co-morbid diseases, including rhinitis and chronic rhinosinusitis. The aim of this study was to determine whether multi-symptom asthma is related to signs of severe asthma, and to investigate the association between multi-symptom asthma and different symptoms of allergic and chronic rhinosinusitis.

Methods

This study analyzed data on asthma symptoms, rhinitis, and chronic rhinosinusitis from the 2008 West Sweden Asthma Study, which is an epidemiologically based study using the OLIN and GA²LEN respiratory and allergy focused questionnaires.

Results

Multi-symptom asthma was present in 2.1% of the general population. Subjects with multi-symptom asthma had more than double the risk of having night-time awakenings caused by asthma compared with those with fewer asthma symptoms (P < 0.001). The prevalence of allergic rhinitis was similar in the fewer- and multi-symptom asthma groups, but nasal blockage and rhinorrhea were significantly increased in those with multi- versus fewer-symptom asthma (odds ratio 2.21; 95% confidence interval 1.64-2.97, versus 1.49; 1.10-2.02, respectively). Having any, or one to four symptoms of chronic rhinosinusitis significantly increased the risk of having multi- versus fewer-symptom asthma (P < 0.01).

Conclusion

An epidemiologically identified group of individuals with multiple asthma symptoms harbour to greater extent those with signs of severe asthma. The degree of rhinitis, described by the presence of symptoms of nasal blockage or rhinorrhea, as well as the presence of any or several signs of chronic rhinosinusitis, significantly increases the risk of having multi-symptom asthma.     

Recurrence of allergic bronchopulmonary aspergillosis after adjunctive surgery for aspergilloma: a case report with long-term follow-up

Background

Coexistence of aspergilloma and allergic bronchopulmonary aspergillosis (ABPA) has rarely been reported. Although the treatment for ABPA includes administration of corticosteroids and antifungal agents, little is known about the treatment for coexisting aspergilloma and ABPA. Furthermore, the impact of surgical resection for aspergilloma on ABPA is not fully understood. Here, we present an interesting case of recurrent ABPA with long-term follow-up after surgical resection of aspergilloma.

Case presentation

A 53-year-old man with a medical history of tuberculosis was referred to our hospital with cough and dyspnea. Imaging revealed multiple cavitary lesions in the right upper lobe of the lung, with a fungus ball and mucoid impaction. The eosinophil count, total serum immunoglobulin E (IgE), and Aspergillus-specific IgE levels were elevated. Specimens collected on bronchoscopy revealed fungal filaments compatible with Aspergillus species. Based on these findings, a diagnosis of ABPA with concomitant aspergilloma was made. Although treatment with corticosteroids and antifungal agents was administered, the patient’s respiratory symptoms persisted. Therefore, he underwent lobectomy of the right upper lobe, which resulted in a stable condition without the need for medication. Twenty-three months after discontinuation of medical treatment, his respiratory symptoms gradually worsened with a recurrence of elevated eosinophil count and total serum IgE. Imaging revealed recurrent bronchiectasis and cavities with mucoid impaction in the right lower lobe, suggesting relapse of aspergilloma and ABPA. Corticosteroids and antifungal agents were re-administered; aspergilloma improved slightly over a 5-year period, and ABPA remained well controlled with low-dose prednisolone (5?mg/day).

Conclusions

We describe the long-term follow-up outcomes of a patient with concomitant ABPA and aspergilloma, who underwent surgical resection for aspergilloma. Physicians should carefully monitor patients with coexisting ABPA and aspergilloma, as the condition may relapse after remission, even despite surgical resection for aspergilloma. Additionally, surgical resection for aspergilloma could result in resolution of ABPA.

     

Acute liver failure: a rare clinical presentation of visceral leishmaniasis

We recently re-examined a case of Visceral Leishmaniasis, in a 36-year-old caucasian immune-competent men with an unusual clinical presentation. Together with symptoms and signs of a severe acute liver involvement, he presented weight loss, huge spleen enlargement, pancytopenia and increased ?-globulin serum level with a high polyclonal peak. He had no fever, but over-abundant night sweats were frequent. The patient was considered to have liver cirrhosis, and the diagnosis of visceral leishmaniosis was made with a year's delay. From this case report we may learn that, despite an unusual clinical presentation, the diagnosis of visceral leishmaniasis should not be excluded when other characteristic signs and symptoms and laboratory abnormalities are present.     

Conformation of an immunoreactive undecapeptide fragment (10–20) of Asp f 1 by NMR and molecular modeling

Summary Allergic bronchopulmonary aspergillosis (ABPA), caused byAspergillus fumigatus, is a complication of allergic asthma. Asp f 1 secreted byA. fumigatus is reported to be a major allergen/antigen involved in pathogenesis of aspergillosis. A 11-mer immunodominant epitope (Leu-Asn-Pro-Lys-Thr⁵-Asn-Lys-Trp-Glu-Asp¹⁰-Lys) of Asp f 1 has shown immunoreactivity with specific IgG and IgE antibodies in the sera of patients with ABPA in ELISA inhibition assay. Various studies have suggested that the peptide has a potential use in the development of ELISA based diagnostic kit for early diagnosis of infections caused byA. fumigatus. In view of these interesting properties of the undecapeptide we have embarked on an investigation of its conformation to understand the relationship between structure and immunoreactivity. NMR and molecular modeling studies of the peptide suggest a structure with a β-turn spanning residues Asn⁶-Glu⁹ in water at pH 4.0, a β-pleated sheet in DMSO and α-helix in 40% HFA.     

Risk factors for asthma and allergy associated with urban migration: background and methodology of a cross-sectional study in Afro-Ecuadorian school children in Northeastern Ecuador (Esmeraldas-SCAALA Study)

Background

This study examined the attitudes and actions of 3415 physician-recruited adults aged ≥ 16 years with asthma in eleven countries who were prescribed regular maintenance therapy with inhaled corticosteroids or inhaled corticosteroids plus long-acting β₂-agonists.

Methods

Structured interviews were conducted to assess medication use, asthma control, and patients' ability to recognise and self-manage worsening asthma.

Results

Despite being prescribed regular maintenance therapy, 74% of patients used short-acting β₂-agonists daily and 51% were classified by the Asthma Control Questionnaire as having uncontrolled asthma. Even patients with well-controlled asthma reported an average of 6 worsenings/year. The mean period from the onset to the peak symptoms of a worsening was 5.1 days. Although most patients recognised the early signs of worsenings, the most common response was to increase short-acting β₂-agonist use; inhaled corticosteroids were increased to a lesser extent at the peak of a worsening.

Conclusion

Previous studies of this nature have also reported considerable patient morbidity, but in those studies approximately three-quarters of patients were not receiving regular maintenance therapy and not all had a physician-confirmed diagnosis of asthma. This study shows that patients with asthma receiving regular maintenance therapy still have high levels of inadequately controlled asthma. The study also shows that patients recognise deteriorating asthma control and adjust their medication during episodes of worsening. However, they often adjust treatment in an inappropriate manner, which represents a window of missed opportunity.     

Animal models of allergic bronchopulmonary aspergillosis

Among the allergic fungi, Aspergillus fumigatus, a saprophytic mold, distributed widely in the environment is a frequently recognized etiologic agent in a number of allergic conditions. Among the different allergic diseases caused by this fungus, allergic bronchopulmonary aspergillosis (ABPA) is by far the most significant one. The immunopathogenesis of this disease is not fully understood. Although several immunomodulatory treatments are available for allergic disease, none of them are applicable or relevant or useful in fungal induced allergy. It is essential to understand the pathogenesis of the disease including the antigen induced immunoregulation and the resulting factors, such as cytokine, chemokines, pathways activating factors, inflammatory and airway remodeling factors need to be understood for intervening with appropriate treatment. Animal models are essential in understanding these features of the disease. Several models of allergic aspergillosis have been developed in recent years in various animals. However, murine models have been studied more carefully and extensively. The exposure to antigen in mice leads to allergy very similar to ABPA with high IgE, elevated peripheral blood and lung eosinophils, pulmonary inflammation, and airway hyperreactivity. The role of various cytokines and chemokines and their receptors were also studied. In addition, immunotherapy and vaccination have been attempted in recent years using the murine model of ABPA. This review covers the murine model of Aspergillus induced allergy and asthma and presented critically our current understanding of the subject and the potential application of such a model in future for developing treatment modalities. This revised version was published online in June 2006 with corrections to the Cover Date.     

Insights into animal models for cell-based therapies in translational studies of lung diseases: Is the horse with naturally occurring asthma the right choice?

Human asthma is a widespread disease associated with chronic inflammation of the airways, leading to loss of quality of life, disability and death. Corticosteroid administration is the mainstream treatment for asthmatic patients. Corticosteroids reduce airway obstruction and improve quality of life, although symptoms persist despite treatment in many patients. Moreover, available therapies failed to reverse the lung pathology present in asthma. Animal models, mostly rats and mice, in which the disease is experimentally induced, have been studied to identify new therapeutic targets for human asthma. Alternative animal models could include horses in which naturally occurring asthma could represent an important step to test therapies, potentially designed around mouse studies, before being translated to human testing. Horses naturally suffer from asthma, which has striking parallels with human asthma. Severe equine asthma (SEA) is characterized by reversible bronchospasms and neutrophil accumulation in the lungs immunologically mediated mainly by Th2. Moreover, the pulmonary remodelling that occurs in SEA closely resembles that of human asthma, making the equine model unique for investigation of tissue repair and new therapies. Cell therapy, consisting on mesenchymal stromal cells (MSCs) and derivatives (conditioned medium and extracellular vesicles), could represent a novel therapeutic contribution for tissue regeneration. Cell therapy may prove advantageous over conventional therapy in that it may repair or regenerate the site of injury and reduce the reaction to allergens, rather than simply modulating the inflammatory process.     

支气管哮喘急性发作期超敏C-反应蛋白、白细胞、中性粒细胞比例检测的意义及比较

探讨超敏C-反应蛋白（hs-CRP）、血白细胞总数（WBC）、中性粒细胞比例（N％）在支气管哮喘（简称哮喘）急性发作期诊治中的临床意义。方法：分析60例患者治疗前及自觉症状缓解时hs—CRP、WBC、N％动态变化情况,观察上述指标在急性发作期的阳性率以及自觉症状缓解时的阴性率。结果：①hs-CRP、N％、WBC在自觉症状缓解时均明显低于哮喘急性发作期（P〈0．05）;②哮喘患者急性发作期hs—CRP、N％阳性率均高于WBC阳性率,且与后者比较均具有统计学差异（P〈0．05）;③哮喘患者经治疗自觉症状缓解时hs-CRP、WBC阴性率均高于N％阴性率,且与后者比较均具有统计学差异（P〈0．05）。结论-血清hs-CRP既可作为哮喘患者急性发作期感染的敏感指标,又是反映急性发作期治疗效果的早期评判指标,比WBC、N％更迅速、敏感。     

Estimation of the Burden of Chronic and Allergic Pulmonary Aspergillosis in India

Background and Objectives

It would be of considerable interest to clinicians if the burden of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA) in India were known. Herein, we estimate the burden of CPA following pulmonary tuberculosis (PTB), and ABPA (and severe asthma with fungal sensitization [SAFS]) complicating asthma.

Methods

We used the population estimates for India from the 2011 census data. The burden of asthma was estimated using three different methods (Global Initiative against Asthma [GINA] report statement, World Health Survey [WHS] estimates, Indian study on the epidemiology of asthma and chronic bronchitis [INSEARCH]). Global and India-specific figures were used for calculating the prevalence of ABPA and SAFS. The World Health Organization estimates were used for calculating PTB rates while the frequency of CPA was assessed from a previously published scoping review. Sensitivity analysis was performed to determine the burden in various scenarios.

Results

The total Indian population in 2011 was 1.2 billion. The asthma prevalence in adults was estimated at about 27.6 (range, 17–30) million. The burden of ABPA ranged from 0.12–6.09 million with different assumptions (best estimate, 1.38 [range, 0.86–1.52] million). The prevalence of SAFS was approximated at about 0.52–1.21 million (best estimate, 0.96 [range, 0.6–1.06] million). The incident TB cases were about 2.1 million while the annual incidence of CPA varied 27,000-0.17 million cases, with different estimates. If the mortality of CPA is estimated as 15% annually, the 5-year prevalence of CPA was placed at 290,147 cases with 5-year prevalence rate being 24 per 100,000.

Conclusion

There is a significant burden of ABPA, SAFS and CPA in India. Prospective community-based studies are required to accurately determine the prevalence of these disorders.     

How to achieve better outcome in treatment of asthma in general practice.

The symptoms of many asthmatic patients are poorly controlled, and there are several reasons why this may be so. Doctors fail to find out about symptoms that asthmatic patients are experiencing. Doctors wrongly assume that regular use of bronchodilators in small doses is satisfactory treatment for asthma and that taking high doses of bronchodilator in an asthma attack may be dangerous. Doctors think that inhaled steroids may be dangerous and are reluctant to use them in effective doses. Doctors do not check that patients can use their inhalers properly and do not make enough use of large volume spacers, the best available method for giving inhaled asthma treatment. Doctors undermine patients'' confidence in advice on treatment by failing to ensure that consistent advice is given and often make the management of asthma more troublesome for the patient than the symptoms of asthma.     

Changes of immunomodulatory cytokines associated with omalizumab therapy for severe persistent asthma

Omalizumab is an anti-IgE monoclonal antibody that was proven effective for the treatment of severe asthma. IgE plays a central role in allergic asthma, and an anti-allergic effect of omalizumab has been confirmed in terms of its impact on Th2 cytokines. The objective of the present study is to determine the influence of omalizumab on clinical parameters and circulating immuoregulatory cytokines. Patients with severe allergic asthma were enrolled and given four months of omalizumab therapy. Changes of symptoms and other parameters were assessed, including the asthma control test (ACT) score, morning peak expiratory flow (PEF), peripheral eosinophil count, total serum IgE, and pulmonary function tests. The use of corticosteroids and short-acting bronchodilators, as well as the number of unscheduled hospital visits, were monitored. Circulating levels of cytokines were analyzed with a multiplex cytokine immunoassay in patients with or without omalizumab therapy. Asthma symptoms (evaluated by the ACT score and morning PEF) improved with omalizumab treatment, while total IgE was elevated. Use of corticosteroids and short-acting bronchodilators and the number of unscheduled hospital visits for exacerbation of asthma were all reduced by omalizumab treatment. The level of macrophage inflammatory protein 1-δ (MIP1-δ) was significantly reduced after omalizumab therapy and was high in patients without omalizumab. IL-16 also tended to decrease with omalizumab therapy. Both MIP1-δ and IL-16 decreased as asthma improved over the 4-month period of omalizumab therapy. These findings suggest that omalizumab may act via IgE-mediated immunoregulation of MIP1-δ and IL-16.     

Deep dermatophytoses in association with atopy anddiabetes mellitus: Majocchi's granuloma tricophyticum ordermatophytic pseudomycetoma?

Two patients presenting with subcutaneous nodules, plaques, papules and ulceration caused by dermatophytes are described in this report. The first case was atopic and had used low dosesystemic corticosteroids intermittently for his asthma. The second case was a poorly controlled and long-standing diabetic patient. The diagnoses were suspected after direct microscopical examinations of the discharge materials which revealed the presence of hyaline hyphae and spores, and histological examination which showed an inflammatory infiltrate with fungal elements in the dermis. Cultures of puncture materials and skin biopsies confirmed the diagnosis identifyingTrichophyton rubrumand T. mentagrophytes var interdigitale,in the first and second case respectively. Antifungal therapy with itraconazole was successful in both patients. The cases are presented to emphasize the possibility of this unusual condition in association with atopy and diabetes mellitus as in profoundly immunosuppressed cases. The nomenclature concerning this type of dermatophyte infections is also discussed. This revised version was published online in June 2006 with corrections to the Cover Date.