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958 Gerhart and Kalaaji Stevens-Johnson syndrome, and toxic epidermal necrolysis. Given these adverse effects, many dermatologists are reluctant to give prophylaxis to patients who are on long-term immunosuppressive therapy for immunobullous and connective tissue diseases. No apparent standard of care exists among dermatologists regarding PCP prophylaxis. Therefore, the aim of this study was to identify the frequency of PCP development in patients with immunobullous and connective tissue disease receiving immunosuppressive therapy. METHODS This study was approved by our institutional review board. We performed a retrospective review of patients receiving long-term immunosuppressive therapy for connective tissue disease or a bullous disorder at our institution from 1980 through 2006, in whom pneumonia developed. We used our institutional medical record registry, cross-index system, and paper chart archives to CAPSULE SUMMARY identify patients. Patients were excluded from analysis if their diagnosis of immunobullous or connective tissue disease was not supported by biopsy specimen, immunofluorescence, or serum test results or if there was no record of a systemic immunosuppressive drug used for treatment of the disease. Immunosuppressive drugs (prednisone, azathioprine, methotrexate, mycophenolate mofetil, hydroxychloroquine, dapsone, intravenous immunoglobulin, sulfasalazine, sulfapyridine, methylprednisolone, and cyclophosphamide) were defined as being used for the dermatologic disease if they were given systemically within 1 month of the diagnosis. Patients with AIDS were not excluded. Clinical data collected included age, other comorbid diseases, and date of death and autopsy findings, if applicable. Dermatologic data included date and type of dermatologic diagnosis, method of diagnosis (biopsy specimen, immunofluorescence staining, serum tests), and immunosuppressive drug regimen (dosage, start date, and stop date). In addition, date and type of pneumonia diagnosis, method of diagnosis (from sputum, bronchoalveolar lavage, biopsy specimen, or other), and presenting symptoms were recorded. If the patient received PCP prophylaxis, the medication, duration, and dose were recorded. d Although only 2.1% of patients with immunobullous or connective tissue disease had development of Pneumocystis carinii pneumonia (PCP) in our study, the mortality in those with PCP was high (43%). d The risk of PCP developing in these patients is not necessarily related to high-dose prednisone but to presence of several risk factors, including pulmonary fibrosis, organ transplantation, and malignancy. d Dermatologists must individually assess each patient for risk factors for PCP when weighing the risks and benefits of PCP prophylaxis. JAM ACAD DERMATOL JUNE 2010 Finally, if PCP did develop, we recorded the duration of immunosuppression before PCP diagnosis, length of hospital stay, and time from PCP diagnosis to death, if applicable. RESULTS Of the patients identified who had a diagnosis of immunobullous or connective tissue disease and were on long-term immunosuppression, 334 had pneumonia at some point during their immunosuppressive treatment and were included in our review. Of the 334 patients, 241 (72.2%) had connective tissue disease and 93 (27.8%) had immunobullous disease. Immunosuppressive medications used in the group included prednisone alone in 148 (44.3%), steroid-sparing drugs alone in 69 (20.7%), and a combination of prednisone and a steroid-sparing drug in 117 (35.0%). Seven patients had a diagnosis of PCP (Table I); none of the 7 had received PCP prophylaxis. Of these 7, one had a bullous disorder (1.0% of all patients with immunobullous disease) and 6 had connective tissue diseases (2.5% of all patients with connective tissue disease), which included systemic lupus erythematosus in two patients and dermatomyositis in 4. Of the 327 patients without PCP, 96 received prophylaxis and 231 did not. The mean age of all 334 patients was 57.6 years; mean age was 62.7 years for the 7 patients with PCP. Smoking history, defined as at least 5 years of smoking, was reported in 48.3% of the total group and in 57% (4 of 7) of the patients with PCP. History of chronic obstructive pulmonary disease was reported in 11.8% of study patients and in 29% (2 of 7) of the patients with PCP. We did not assess age, smoking, or chronic obstructive pulmonary disease in the general population during the same period. The mean (SD) number of significant comorbid conditions for the 327 patients without PCP was 2.3 (1.0), whereas for the 7 patients with PCP the mean (SD) number of comorbid conditions was 4.0 (2.2). All 7 patients with PCP had multiple comorbid conditions: two patients had malignancies, two had undergone renal transplantation, and 3 had
JAM ACAD DERMATOL VOLUME 62, NUMBER 6 Table I. Clinical data for the 7 patients with a diagnosis of Pneumocystis carinii pneumonia Patient Diagnosis 1 BP Prednisone, 40 mg/d; methotrexate, Immunosuppressive regimen Duration, d* 2.5-12.5 mg/wk pulmonary disease (two with interstitial fibrosis and one with pneumonia) (Table I). Five of the 7 were taking at least 30 mg/d of prednisone at some point during immunosuppressive treatment, and prednisone dosage ranged from 15 to 60 mg/d. The time from beginning immunosuppressive medication to PCP diagnosis ranged from 48 to 253 days, and 5 patients had PCP development within 3 months of starting immunosuppressive treatment. Six of 7 patients were admitted to the hospital for hypoxia or respiratory failure resulting from PCP. Five patients died; survival in these 5 varied from 8 days to 12 years after PCP diagnosis. Three (43%) of the 7 patients died within 1 month of the PCP diagnosis: two from respiratory arrest caused by PCP and one from respiratory failure caused by a combination of PCP, pulmonary embolism, and disseminated intravascular coagulation. Dermatologic data PCP data Comorbid conditions 253 Bladder cancer, HTN, AS, Paget disease, macular degeneration, MAC 2 SLE Prednisone, 60 mg/d 62 Lupus nephritis after renal transplantation, HTN, CAD, hyperlipidemia, 3 SLE Methylprednisolone, 16 mg/d; MM, 750 mg, 23/d cataracts, obesity 124 Lupus nephritis after renal transplantation, HTN, hyperlipidemia, myogenic bladder, splenectomy, congential hydronephrosis, EBV, Listeria septicemia 4 D Prednisone, 15 mg/d 50 Acute tubular necrosis, interstitial pulmonary fibrosis 5 D Prednisone, 20-30 mg/d 63 Renal cell carcinoma, interstitial pulmonary fibrosis 6 D Prednisone, 25-40 mg/d; 48 Hypothyroidism, azathioprine, 75 mg/d 7 D Prednisone, 60 mg/d; azathioprine, 200 mg/d glaucoma 75 Hypothyroidism, HSV pneumonia, arrhythmia Gerhart and Kalaaji 959 Reason for hospitalization/ duration, d Survival Prophylaxis PCP/17 3 y None PCP/26 12 y None EBV/31 Living None PCP/24 20 d None PCP/19 8 d None PCP/19 18 d None PCP, HSV/8 Living None AS, Aortic stenosis; BP, bullous pemphigoid; CAD, coronary artery disease; D, dermatomyositis; EBV, Epstein-Barr virus; HSV, herpes simplex virus; HTN, hypertension; MAC, Mycobacterium avium complex; MM, mycophenolate mofetil; PCP, Pneumocystis carinii pneumonia; SLE, systemic lupus erythematosus. *Duration of immunosuppression before PCP diagnosis. DISCUSSION PCP is a major cause of morbidity and mortality in immunocompromised hosts. Dermatologists are often reluctant to use sulfa-based medications for PCP prophylaxis for fear of severe drug reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Data describing how often PCP prophylaxis is used for dermatologic patients are lacking. In this study, we reviewed the cases of patients who had an immunobullous or connective tissue disease and were started on immunosuppressive therapy who also had development of pneumonia. Six of the 7 patients in whom PCP developed were receiving immunosuppressive medication for connective tissue disease, and only one patient had a diagnosis of immunobullous disease. Although the majority of the patients in this study had connective tissue disease, the percentage of these patients who
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