Oral Prednisolone Therapy Research Articles

Experience of Epidural Steroids in Transverse Myelitis -A case report-

Transverse myelitis is a focal inflammatory disorder of the spinal cord characterized by motor, sensory, and autonomic dysfunction. A 41-year-old man with transverse myelitis and no pre-existing neurologic disease presented with hypesthesia, numbness, weakness in the both lower extremities, back pain, decreased libido, constipation, and dysuria. A MRI test showed intramedullary high signal intensity between T4 and T8 on a T2-weighted image. After high-dose intravenous methylprednisolone and oral prednisolone therapy, he showed facial swelling and acneiform eruption. Therefore, we injected 40 mg methylprednisolone via an epidural route. A 7-dose serial treatment improved most symptoms. A follow up MRI showed radiological improvement. We report a case of transverse myelitis treated by epidural steroids.

Hypereosinophilic Syndrome in a Medical Center in Taiwan-an Analysis of Fourteen Cases

Objectives: Hypereosinophilic syndromes are disorders with persistent overproduction of eosinophils. The diseases are characterized by damage to multiple organs due to eosinophilic infiltration and mediator release. This study aimed to investigate the clinical manifestation, frequency of organ involvement, treatment and outcome among patients with hypereosinophilic syndrome in a single medical center in Taiwan. Material and Methods: Patients admitted to our hospital due to hypereosinophilic syndrome from December 1986 to July 2007 were enrolled in this study. The initial symptoms, spectrum of organ involvement, total eosinophil count, therapeutic regimen and clinical outcome were retrospectively reviewed and documented. Result: A total of 14 cases were diagnosed with hypereosinophilic syndrome. The average age was 44.1 years old. The male/female ratio was 3.7: 1. The average duration of symptom onset to diagnosis was 14.3 months. The most common initial symptoms were skin rashes (50%), followed by gastrointestinal symptoms (abdominal pain and diarrhea, 36%) and fever (36%). The most frequently involved organ was cutaneous involvement (50%), followed by gastrointestinal involvement (43%) and peripheral vascular involvement (36%). The frequency of cardiovascular involvement was lower (14%) than in western countries. All patients received corticosteroid treatment initially. Most patients required long-term oral prednisolone and immunosuppressive therapy. Conclusion: This study displays clinical characteristics of hypereosinophilic syndrome in Taiwan. Cutaneous and gastrointestinal systems are the most frequently involved organs. A high clinical suspicious index and early biopsy of the involved organ helps in diagnosis of this rare disease.

Renal amyloidosis associated with extracapillary glomerulonephritis and vasculitis in a patient with inflammatory bowel disease treated with infliximab

A 70-year-old woman with an 11-year history of indeterminate inflammatory bowel disease developed rapidly progressive glomerulonephritis (RPGN) 3 months after the initiation of infliximab therapy. A renal biopsy showed Congo red-positive homogenous deposits in the mesangial area, glomerular capillary walls and arterial walls. Cellular and fibrocellular crescents were observed in 7 of 28 functioning glomeruli. There were findings of active tubulointerstitial nephritis and vasculitis of the small arteries. On electron microscopy, amyloid fibrils were observed in the deposits. Immunohistochemistry showed positive staining for amyloid A (AA) protein. After cessation of infliximab therapy, she was treated with methylprednisolone pulse therapy followed by oral prednisolone therapy. Thereafter, her RPGN was improved. This is a rare case of co-existent focal extracapillary glomerulonephritis with vasculitis and AA renal amyloidosis. Considering the temporal association of drug use with new onset of RPGN in our patient, we suggest a causal link between infliximab and RPGN due to extracapillary glomerulonephritis and vasculitis.

Simultaneous determination of prednisolone, prednisone, cortisol, and cortisone in plasma by GC–MS: Estimating unbound prednisolone concentration in patients with nephrotic syndrome during oral prednisolone therapy

Individual variability of the pharmacokinetics of prednisolone based on the unbound concentration in plasma is of significant clinical consideration. The unbound concentrations of prednisolone were measured in 10 patients with nephrotic syndrome, two patients with systemic lupus erythematosus, and one patient with dermatomyositis by examining protein bindings of prednisolone on one or more occasions during prednisolone treatment. In this study, plasma concentrations of prednisolone, prednisone, cortisol, and cortisone were simultaneously analyzed by GC–MS by using stable isotope-labeled internal standards. Equilibrium dialysis was employed to accurately estimate the unbound fractions of prednisolone in plasma. The unbound fraction of prednisolone changed depending on plasma total prednisolone concentration and plasma albumin concentration. The unbound fraction of prednisolone ( Y) is calculated: Y = (−0.0101 x′ + 0.0736) x + 10.23, where x′ is the plasma albumin concentration and x is the total prednisolone concentration. The estimated concentrations of unbound prednisolone by using the above equation were in good agreement with the measured concentrations of unbound prednisolone. Since the protein binding of prednisolone did not change in the presence of prednisone (114.0 ng/ml), it appeared that prednisone produced from the therapeutic dose of prednisolone did not affect the unbound fraction of prednisolone.

Two courses of rituximab (anti‐CD20 monoclonal antibody) for recalcitrant pemphigus vulgaris

Pemphigus vulgaris (PV) is a severe autoimmune blistering disease involving the skin and mucous membranes. The response to therapy varies greatly amongst patients and treatment may be challenging. Rituximab is a chimeric monoclonal antibody that selectively targets cell surface antigen CD20, thus depleting mature B cells in vivo. We report the results of rituximab treatment in two patients with severe PV. In both patients, high-dose oral prednisolone and adjuvant therapy with intravenous immunoglobulins and mycophenolate mofetil failed to control disease activity. Consequently, the patients were treated with two courses of four weekly intravenous infusions of rituximab (375 mg/m(2)) with a 6-month interval. Clinical improvement was already noticeable 3-6 weeks after the first infusion. After the second course, complete remission was achieved. Oral prednisolone was reduced and treatment with mycophenolate mofetil was continued. The patients remained in full remission 6 months after the last rituximab infusion. These cases suggest that two courses rather than a single course of rituximab may be a preferable mode of treatment. Rituximab should be considered as a promising treatment option for recalcitrant PV.

Effect of a Short Course of Prednisolone in Infants With Oxygen-Dependent Bronchopulmonary Dysplasia

The purpose of this work was to determine whether oral prednisolone is effective in weaning infants with bronchopulmonary dysplasia, after 36 weeks' postmenstrual age, off supplemental oxygen and to identify factors associated with successful weaning. Data were abstracted from a standardized prospectively collected database at the John Dempsey Hospital NICU. Logistic regression and receiver operating curve analyses were used. Of 385 infants, 131 (34%) received oral prednisolone and 254 (66%) did not. There was no significant difference in race, gender, birth weight, or gestational age between the groups receiving and not receiving oral prednisolone. Infants in the oral prednisolone group were more likely to have received previous dexamethasone therapy, had longer duration of mechanical ventilation, had longer length of hospital stay, and were more likely to be discharged from the hospital on oxygen. Of those in the oral prednisolone group, 63% responded to treatment. Pulmonary acuity score and PCO2 were the only parameters that remained significant on multiple logistic regression analyses. The oral prednisolone-responsive group had a lower pulmonary acuity score compared with the oral prednisolone-nonresponsive group. A pulmonary acuity score value of < or = 0.5 had a sensitivity of 20% and specificity of 97.4%, with positive and negative predictive values of 94.1% and 42.1%, respectively. Capillary PCO2 values were significantly lower in the oral prednisolone-responsive group compared with the oral prednisolone-nonresponsive group. In predicting a successful response to oral prednisolone, a capillary PCO2 value of < 48.5 mmHg had a sensitivity of 50% and specificity of 89.7%, with positive and negative predictive values of 89.1% and 51.8%, respectively. Oral prednisolone therapy is effective in weaning off supplemental oxygen in a postterm infant with oxygen-dependent bronchopulmonary dysplasia who has a pulmonary acuity score of < 0.5 and PCO2 of < 48.5 mmHg. In addition, if a single course of prednisolone fails, there is no clear benefit of using multiple courses.

Conjunctival Involvement in Chronic Recurrent Multifocal Osteomyelitis

To report a case of chronic recurrent multifocal osteomyelitis (CRMO) with conjunctival involvement. Retrospective chart review. A 10-year-old girl who complained of fatigue and debilitating pain in both hips and legs for >1 year had recurrent episodes of redness and discharge in both eyes with little response to different topical medications. The diagnosis of CRMO was confirmed with the help of magnetic resonance imaging, bone scan, and bone biopsy results. She had moderate hyperemia and multiple discrete salmon-colored lesions in both palpebral and fornical conjunctivae. Biopsy revealed chronic inflammatory infiltration composed predominantly of lymphocytes forming a follicular pattern. Conjunctival lesions worsened during relapses of skeletal symptoms, improved during remission, and resolved shortly after the initiation of oral prednisolone therapy. No recurrence was observed during 16 months of follow-up. Salmon-colored conjunctival lesions may accompany CRMO and respond favorably to systemic steroid therapy.

Effects of Bisphosphonates on Fracture Incidence and Bone Metabolism in Rheumatoid Arthritis Patients in General Practice Taking Long-Term Corticosteroid Therapy

There is a risk that disturbances of activities of daily living (ADL) due to rheumatoid arthritis (RA) are increased by the occurrence of fractures, including vertebral compression fractures and femoral neck fractures, in RA patients receiving oral corticosteroid therapy. Bisphosphonates are most commonly used in the treatment of postmenopausal osteoporosis. In a large-scale, randomized, double-blind, placebo-controlled study that was performed to assess the prophylactic efficacy of bisphosphonates, alendronic acid decreased the incidence of vertebral fractures by approximately 50% compared with placebo in postmenopausal patients. A similar result has also been reported with risedronic acid. The present long-term retrospective study evaluated the effects of alendronic acid and risedronic acid therapy on development of new vertebral/non-vertebral fractures in RA patients receiving long-term oral prednisolone therapy at an average dose of 5 mg/day. The subjects were 138 general practice patients aged 50-79 years with RA (alendronic acid group 80; risedronic acid group 58) who received oral prednisolone at a dose of 2-15 mg/day for at least 1 year combined with bisphosphonate therapy (alendronic acid 5 mg/day or risedronic acid 2.5 mg/day) for at least 10 months. Patients with five or more vertebral fractures at the start of bisphosphonate therapy were excluded from the study. Vertebral fractures were detected by obtaining plain x-ray films of the thoracic and lumbar spines at the start of bisphosphonate therapy and on completion of follow-up. We measured the incidence of new fractures, the speed of sound (SOS) at the calcaneus as measured by quantitative ultrasound, and levels of crosslinked N-telopeptide of type I collagen (NTX), a marker of bone resorption. The percentage change at each measuring point was tested using the paired t-test. The incidence of new fractures was compared between groups using the Cox proportional hazard model. The incidence of new vertebral fractures was 6.3% in the alendronic acid group and 13.8% in the risedronic acid group; the incidence of new non-vertebral fractures was 6.3% and 12.1%, respectively. The incidence of any fracture was significantly higher and severe fractures tended to be more common in the risedronic acid group. Analysis by the Cox proportional hazard model revealed a significant difference between the two groups with respect to the cumulative incidence of new fractures (p = 0.0386). The SOS of the calcaneus showed no appreciable difference between the two groups. NTX measurements indicated that antiresorptive activity was maintained from 6 months of treatment onwards in the alendronic acid group but not in the risedronic acid group. These findings suggest that alendronic acid has a stronger prophylactic effect against fractures than risedronic acid in RA general practice patients taking long-term corticosteroid therapy.

Acute retinal necrosis by cytomegalovirus in an immunocompetent adult: case report and review of the literature

A rare case of acute retinal necrosis caused by cytomegalovirus in an immunocompetent adult, diagnosed by polymerase chain reaction of vitreous aspirate, with good visual outcome after intravitreal and intravenous ganciclovir and oral prednisolone therapy, is reported. A 50-year-old healthy lady presented with redness and diminution of vision in her right eye of 10 days duration. She had anterior chamber inflammation, marked vitritis, and anterior retinal necrosis in the right eye. Blood and other investigations did not reveal any infectious diseases and HIV testing was negative. The retinal lesions and panuveitis resolved with treatment. Two months later she developed retinal detachment which was treated successfully. The best-corrected vision was 6/12 in the right eye. Seven cases of cytomegalovirus ocular infection in immunocompetent healthy adults, reported in the literature, were reviewed. The different presentations of this disease and the importance of suspecting this causative agent are highlighted.

Formaldehyde‐induced urticarial vasculitis

A 40-year-old male medical student presented with urticarial vasculitis secondary to occupational formaldehyde exposure. Serum sickness and delayed pressure urticaria also featured prominently during his illness. Initial symptom control was achieved with oral prednisolone (25 mg/day tapered to zero over 2 weeks) and oral antihistamine therapy (fexofenadine 180 mg once daily, promethazine 20 mg once daily, ranitidine 150 mg twice daily); however, subsequent exposures to formaldehyde produced transient symptom flares that broke through the prednisolone cover. A complete recovery occurred only after strict elimination of all exposure to formaldehyde, both occupationally and in the home environment, was achieved.

Tonsillectomy in the treatment of pediatric Henoch-Schönlein nephritis

The exact pathophysiology of HSN remains to be elucidated. Hence, a therapeutic strategy that enables curative treatments for all the various grades of HSN patients has yet to be established. We report our experience performing tonsillectomy combined with steroid therapy for 16 pediatric proteinuric Henoch-Schönlein nephritis (HSN) patients. All patients exhibited hematuria and proteinuria in their first HSN attack with the mean age of onset 7.7 years (range 4.75 - 13.9 years). Nine patients were diagnosed with clinically severe HSN presenting with massive proteinuria (> 1 g/m(2)/day). Renal biopsy findings performed in 6 patients were Grade II (3), Grade III (2) and Grade IV (1) according to the International Study of Kidney Diseases in childhood classification. Tonsillectomy was performed after 1-4 cycles of methylprednisolone pulses during oral prednisolone (0.5 - 1.5 mg/kg/day) therapy. In 2 patients, oral cyclophosphamide therapy was added before the tonsillectomy. The interval between the onset of HSN and tonsillectomy was 97.4 +/- 24.5 days (range 27 424 days). In all patients, proteinuria had disappeared by 6 months after the tonsillectomy and the urine findings had normalized. The interval between therapy initiation and complete remission was 9.6 +/- 2.0 months (range 2 - 26 months). Over follow-up periods of 4.9 +/- 0.6 years (range 2.2 - 9.3 years), no recurrences of Henoch-Schonlein purpura or HSN were observed. There was a significant correlation between early tonsillectomy performance and decreased time until normalization of the urine findings, indicating that the tonsils may have pivotal roles in the initiation and progression of HSN. Their elimination might promote the reversal of nephritis. Although this study is retrospective, we suggested that tonsillectomy at an early stage of HSN may be beneficial by shortening the period of illness and contributing to clinical recovery. Randomized controlled trials will be needed to confirm this supposition.

A prospective, randomized, double‐blind trial to evaluate the role of a short reducing course of oral corticosteroid therapy in the treatment of chronic prostatitis/chronic pelvic pain syndrome

To assess the validity of our observational experience that a short course of oral prednisolone therapy might be of value in the management of symptoms of chronic pelvic pain syndrome (CPPS) in men. Twenty-one men with CPPS (inflammatory or non-inflammatory) for > or =6 months, and who had failed to improve with standard antibiotic therapy, were randomized to receive either a 1-month reducing course of oral prednisolone (nine) or an equivalent placebo regimen (12 men). The outcome measures used were the McGill Pain Questionnaire, the Hospital Anxiety and Depression Scale (HADS), General Health Questionnaire-30 (GHQ-30) and the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI), which were completed at baseline and 3 months. Outcomes were analysed for the 18 patients (six treated, 12 placebo) who completed the 3 months of follow-up. At both baseline and 3 months, respectively, there was no statistically significant difference between the groups in the NIH-CPSI total score (P = 0.48 and 0.62; Mann-Whitney U-test), or in the HADS (anxiety, P = 0.85 and 0.67; depression P = 0.96 and 0.74), and there was no significant improvement or deterioration over time. Although not statistically significant, there was a trend to improvement in the depression score for the active group (P = 0.13). However, the clinical significance is doubtful, as both baseline and follow-up depression scores were within the normal range. No patient had clinically negative changes in depression. A 3-month follow-up analysis was not possible for the McGill Pain Questionnaire or GHQ-30 as not all patients completed the questionnaire. Whilst the study showed no clinical benefit of using corticosteroids in the management of CPPS, the few patients recruited limited the validity of firm conclusions from the data. There was a trend towards an improvement of depression levels amongst subjects. The study highlights the difficulties of recruitment and illustrates the complex psychological profiles of patients with CPPS.

A Case of Henoch-Schönlein Purpura Associated with Diffuse Large B Cell Lymphoma

A 69-year-old female was referred to our institution due to abdominal pain and palpable purpura on both buttocks and legs. A skin biopsy of her purpura revealed granulocyte infiltration and leucocytoclasia around the arterioles and venuoles at the dermis, as well as an elevated serum immunoglobulin A level, hematuria and proteinuria. Therefore she was diagnosed with Henoch-Schonlein purpura. She had been diagnosed with diffuse large B cell lymphoma after a biopsy of her left inguinal lymph node 12 years ago and received 6 cycles of CHOP (cyclophosphamide, doxorubici n, vincristine and prednisone) chemo- therapy, which was followed by a complete remission. Abdominal and chest CT revealed multiple lymph node enlargement and bowel wall thickening at the ileocecal area, and lesions were observed in a whole body PET CT scan. Recurrence of the diffuse large B cell lymphoma was confirmed by a biopsy of the ileocecal area via colonoscopy. The purpura was improved after oral prednisolone therapy and etopo- side, oxaliplatin and ifosfamide salvage combination chemotherapy was used to treat the lymphoma.

Granulomatous rosacea-like demodicidosis

Demodicidosis may present as pityriasis folliculitis, papulopustular lesions, rosacea-like eruptions, and granulomatous rosacea-like eruptions. We report a case of demodex granuloma presenting with recurrent granulomatous rosacea-like papules on the face in a middle-aged woman. The diagnosis of demodicidosis was made by finding extrafollicular mites in the perifollicular inflammatory infiltrate. The papules resolved after 3 weeks of systemic and topical metronidazole, and low-dose oral prednisolone therapy. In summary, demodex granuloma may be mistaken for granulomatous rosacea-like papules. Correct diagnosis can be facilitated by finding extrafollicular demodex mites in skin biopsy specimens.

Usefulness of oral corticosteroid in Rosai?Dorfman disease

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a benign self-limiting disorder of unknown aetiology, which is frequently mistaken for lymphoma. There is no consensus as to the proper management of this disorder. In the past, potentially harmful treatments, such as antineoplastic drugs, have been advocated. We describe a 25-year-old woman with RDD who has had a remarkably favourable response to oral prednisolone therapy. Our observation strengthens the conclusions of previous case reports as to the effectiveness of corticosteroids in this condition. This article is aimed at creating awareness among clinical oncologists about this pseudolymphomatous disorder and emphasizing the therapeutic role of corticosteroids.

Long-Term Outcome of Autoimmune Pancreatitis After Oral Prednisolone Therapy

Background: We investigated the long-term outcome of autoimmune pancreatitis (AIP) including morphological changes in the pancreas, pancreatic duct, biliary tract, pancreatic function, and changes in the clinical manifestations after oral prednisolone (PSL) therapy. Methods: We prospectively followed 12 patients for a period of over 12 months (median follow-up period: 41 months; range: from 13 to 133 months). All twelve patients were treated with PSL. The morphological findings consisted of pancreatic enlargement (n = 12), irregularly narrowed main pancreatic duct (n = 12), and bile duct stricture (n = 10) and salivary gland swelling was observed in six patients. The initial dose of PSL was 30-40 mg/day, and it was subsequently tapered. Results: All 12 patients responded to PSL therapy. The enlargement of the pancreas and the irregularly narrowed main pancreatic duct improved to almost normal. Pancreatic atrophy developed in four of them (4/12, 33%) but, no pancreatic calcification was observed in any of the patients. The bile duct stricture improved to various degrees in all 10 patients , but it persisted in the lower part of the bile duct in four of them (4/10, 40%). The salivary gland swelling also improved after PSL therapy. There were no recurrences of the enlargement of the pancreas or irregularly narrowed main pancreatic duct after PSL therapy, but the bile duct stricture recurred in one case, and in three cases there was a relapse of the salivary gland swelling that required a temporary increase in PSL dose during tapering. No deterioration of pancreatic exocrine function was detected in any of the patients. A malignant tumor was diagnosed in two patients during PSL therapy: early gastric cancer in one and rectal cancer in the other. All patients are alive. Conclusions: AIP treated with PSL has a favorable long-term outcome based on the morphological findings and assessments of pancreatic function. However, since some patients developed a malignancy during PSL therapy, and strict follow up should be part of the management of AIP.

Long-term Outcome of Autoimmune Pancreatitis after Oral Prednisolone Therapy

We investigated the long-term outcome of autoimmune pancreatitis (AIP) including morphological changes in the pancreas, pancreatic duct, biliary tract, pancreatic function, and changes in the clinical manifestations after oral prednisolone (PSL) therapy. We prospectively followed 12 patients for a period of over 12 months (median follow-up period: 41 months; range: from 13 to 133 months). All twelve patients were treated with PSL. The morphological findings consisted of pancreatic enlargement (n=12), an irregularly narrowed main pancreatic duct (n=12), and bile duct stricture (n=10), and salivary gland swelling was observed in six patients. The initial dose of PSL was 30-40 mg/day, and it was subsequently tapered. All 12 patients responded to PSL therapy. The enlargement of the pancreas and the irregularly narrowed main pancreatic duct improved to almost normal. Pancreatic atrophy developed in four of them (4/12, 33%), but no pancreatic calcification was observed in any of the patients. The bile duct stricture improved to various degrees in all 10 patients , but it persisted in the lower part of the bile duct in four of them (4/10, 40%). The salivary gland swelling also improved after PSL therapy. There was no recurrence of enlargement of the pancreas or irregularly narrowed main pancreatic duct after PSL therapy, but the bile duct stricture recurred in one case, and in three cases there was a relapse of salivary gland swelling that required a temporary increase in PSL dose during tapering. No deterioration of pancreatic exocrine function was detected in any of the patients. A malignant tumor was diagnosed in two patients during PSL therapy: early gastric cancer in one and rectal cancer in the other. All patients are alive. AIP treated with PSL has a favorable long-term outcome based on the morphological findings and assessments of pancreatic function. However, since two of the twelve patients developed a malignancy during PSL therapy, strict follow up should be part of the management of AIP.

Pulsatile ocular blood flow change after treatment with systemic steroid in patients with Graves' ophthalmopathy

Our previous study has demonstrated an impairment of pulsatile ocular blood flow (POBF) in patients with Graves'ophthalmopathy (GO). Here we further evaluate the haemodynamic change in GO patients after systemic steroid. In a prospective, interventional, consecutive clinical case series, all patients with active and moderately severe GO who underwent systemic steroid treatment were evaluated. The change of POBF and the clinical activity and severity of the disease were assessed. In total, 11 patients underwent intravenous methylprednisolone pulse therapy followed by 2-month oral prednisolone therapy. POBF improved from a mean value of 476.5 to 614.7 microl/min (P<0.001) after treatment. Likewise, the mean clinical activity score reduced from 4.8 to 1.6. However, systemic steroid had less effect on the severity of GO. It also revealed that there is a greater improvement of POBF in those with more clinical activity score (>4) at the onset. Following treatment with systemic steroid we have demonstrated a significant improvement in POBF in patients with GO.

Intractable chronic inflammatory demyelinating polyneuropathy treated successfully with ciclosporin

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous disorder and both clinical course and response to treatment vary widely. Because of the propensity for relapse, CIDP requires maintenance therapy...

Aspergillosis in Amazon Parrots After Corticosteroid Therapy for Smoke-inhalation Injury

Seven blue-fronted Amazon parrots (Amazona aestiva aestiva), housed in 1 aviary, were presented within 8 hours of exposure to fire and smoke. The parrots exhibited variable degrees of dyspnea that developed between 1 and 4 hours after the exposure. Clinical signs of dyspnea resolved within hours after treatment with corticosteroids and furosemide. Because of a misunderstanding by the owner, oral prednisolone therapy was continued daily for 20 days. Within 14–20 days, 5 birds developed signs of severe dyspnea and 3 birds died or were euthanatized. Results of necropsy revealed severe mycotic airsacculitis and pneumonia due to Aspergillus fumigatus. Prolonged corticosteroid treatment in these birds may have caused immunosuppression, predisposing them to development of aspergillosis.