Interstitial fibrosis increases the risk of end-stage kidney disease in patients with lupus nephritis.

OBJECTIVE: To evaluate the risk of end-stage kidney disease (ESKD) in lupus nephritis (LN) patients using tubulointerstitial lesion scores. METHODS: Clinical profiles and histopathological presentations of 151 biopsy-proven LN patients were retrospectively examined. Risk factors of ESKD based on characteristics and scoring of their tubulointerstitial lesions (e.g. interstitial inflammation [II], tubular atrophy [TA], and interstitial fibrosis [IF]) were analyzed. RESULTS: The mean age of 151 LN patients was 36 years old, and 136 (90.1%) were female. The LN cases examined included: class I/II (n = 3, 2%), class III/IV (n = 119, 78.8%), class V (n = 23, 15.2%), and class VI (n = 6, 4.0%). The mean serum creatinine level was 1.4 mg/dl. Tubulointerstitial lesions were recorded in 120 (79.5%) patients. Prior to receiving renal biopsy, 9 (6.0%) patients developed ESKD. During the follow-up period (mean, 58 months), an additional 47 patients (31.1%) progressed to ESKD. Multivariate analyses identified serum creatinine (hazard ratio [HR]: 1.7, 95% confidence interval [CI]: 1.42-2.03, p < 0.001) and IF (HR: 3.2, 95% CI: 1.58-6.49, p = 0.001) as independent risk factors of ESKD. Kaplan-Meier analysis further confirmed a heightened risk of ESKD associated with IF. CONCLUSION: Tubulointerstitial involvement is commonly observed in histopathological presentation of LN. However, IF, rather than II, or TA, was found to increase the risk of ESKD in our cohort. Therefore, to predict renal outcome in LN patients prior to adjusting immunosuppressive treatment, degree of IF should be reviewed.

Risk Factors and Incidence of Serious Infections in Patients With Systemic Lupus Erythematosus Undergoing Rituximab Therapy.

OBJECTIVE: To evaluate the risk and protective factors of serious infection (SI) in patients with systemic lupus erythematosus (SLE) within 180 days of rituximab (RTX) treatment. METHODS: Patients with SLE treated with RTX were analyzed. SI was defined as any infectious disease requiring hospitalization. The clinical characteristics, laboratory profiles, medications, and incidence rate (IR) are presented. Multivariate Cox proportional hazards models and Kaplan-Meier analysis for risk factors of SI were performed. RESULTS: A total of 174 patients with SLE receiving RTX treatment were enrolled. The overall IR of SIs was 51.0/100 patient-years (PYs). Pneumonia (30.4/100 PYs), followed by soft tissue infections, intra-abdominal infections, and Pneumocystis jiroveci pneumonia (all 6.1/100 PYs) were the leading types of SIs. Twelve patients died during the 180-day follow-up (crude mortality rate: 14.6/100 PYs). Chronic kidney disease (CKD), defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 (hazard ratio [HR] 2.88, 95% CI 1.30-6.38), and a background prednisolone (PSL) equivalent dosage ≥ 15 mg/day (HR 3.50, 95% CI 1.57-7.78) were risk factors for SIs among all patients with SLE. Kaplan-Meier analysis confirmed the risk of SI for patients with SLE with CKD and a background PSL equivalent dosage ≥ 15 mg/day (log-rank P = 0.001 and 0.02, respectively). Hydroxychloroquine (HCQ) reduced the risk of SIs in patients with SLE (HR 0.35, 95% CI 0.15-0.82; log-rank P = 0.003). CONCLUSION: SI was prevalent in patients with SLE after RTX treatment. Patients with SLE with CKD and high-dose glucocorticoid use required constant vigilance. HCQ may reduce the risk of SI among patients with SLE administered RTX.

[Association Between Sleep Patterns and Diurnal Blood Pressure Variation and Its Predictors in Women With Systemic Lupus Erythematosus].

BACKGROUND: Sleep disturbances and hypertension are common health issues in patients with systemic lupus erythematosus (SLE). Limited information is available regarding the objective sleep quality and the variation of diurnal blood pressure (BP) in patients with SLE. Moreover, the relationship between sleep patterns and diurnal BP variation in SLE patients is not clear. PURPOSE: To explore the subjective/objective sleep patterns and the diurnal BP variation in women with SLE, to identify the factors associated with diurnal BP variation, and to identify the predictors of this variation. METHODS: A cross-sectional, descriptive, correlational study was conducted and 42 women with SLE were recruited. Participants completed the Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale, and Brief Pain Inventory. Rheumatologists rated current lupus disease activity. Additionally, the participants wore a wrist actigraph for 7 consecutive days and underwent 24h ambulatory BP monitoring for one day. RESULTS: The mean Global PSQI score was 7.74 ± 3.21; 69% of the participants reported poor subjective sleep quality; the actigraphy-measured sleep efficiency was 85.29 ± 5.95%; and 42.9% had poor objective sleep quality. Total sleep time at night was positively associated with diurnal change in diastolic BP (r = .315. p < .05) and pain severity was negatively associated with diurnal change in systolic BP (r = -.430, p < .01) and diastolic BP (r = -.371, p < .05). Multiple linear regression analysis was used to predict diurnal BP variation. Moreover, pain was a significant predictor of diurnal change in systolic BP (ß = -0.397, p < .01) and diurnal change in diastolic BP (ß = -0.325, p < .05). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The findings of the present study suggest that healthcare professionals should routinely evaluate sleep quality and pain in SLE patients. Improving both the poor sleep and pain management of these patients is clinically important. Further studies of the association between pain management and diurnal BP variation are needed.

Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Undergoing Biologics Treatment.

Background: Immunosuppressants can induce hepatitis B virus (HBV) reactivation; however, informative data about the risk of different immunosuppressive regimens, including biologics, on HBV reactivation (HBVr) among patients with rheumatoid arthritis (RA) are incomplete. Methods: Among 2334 RA patients who had available hepatitis B surface antigen (HBsAg) data, 123 patients positive for HBsAg who were not receiving anti-HBV prophylaxis were enrolled. These patients were undergoing varied mono or combination immunosuppressive therapy, including 36 who were receiving biological disease-modifying antirheumatic drugs (bDMARDs). Results: During 3459 person-months of follow-up, 30 (24.4%) patients developed HBVr. The multivariate Cox proportional hazard models showed that glucocorticoid significantly increased the risk of HBVr. Among all kinds of immunosuppressive treatments, glucocorticoid in combination with bDMARDs and synthetic disease-modifying antirheumatic drugs (sDMARDs) had the highest risk of HBVr (adjusted hazard ratio [HR] = 5.14; 95% confidence interval [CI] = 1.77-14.92; P = .003). Rituximab had the greatest risk for HBVr (adjusted HR = 16.51; 95% CI = 1.82-149.67; P = .01) among the patients who received bDMARDs. Conclusions: Glucocorticoid has a detrimental effect on HBVr in RA patients. Antiviral prophylactic strategies should be justified according to the risk of HBVr under different combinations of immunosuppressive therapy in rheumatic patients.

Risk factors for mortality in systemic lupus erythematosus patients: Analysis of adult and pediatric cohorts in Taiwan.

BACKGROUND: Overall survival of systemic lupus erythematosus (SLE) patients significantly increased in recent decades, however, the relative risk of mortality is still high. Long-term survival outcome of pediatric SLE remains unclear. This study aims to explore the long-term survival rate and its predictors in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective, hospital-based cohort study was performed between 2004 and 2018 in a tertiary referral medical center in Taiwan. Data on comorbidities, medications, and causes of admission were collected for risk factor analysis using time-dependent multivariate Cox proportional hazards models. RESULTS: A total of 2392 adults and 115 pediatric SLE patients were enrolled (female, n = 2157 and 95, respectively). The 10-year survival rates were 93.2%, 90.2%, 98.9%, and 100% in adult women, adult men, girls, and boys with SLE, respectively. The overall mortality rate was 2.09 case/100 patient-years (PY) for male SLE and 1.39 case/100 PY for female SLE patients. Male SLE patients did not have a statistically significantly higher mortality rate than female SLE patients in each age stratification. Infectious disease (n = 119), heart failure (n = 21), and cerebrovascular accident (n = 14) were the leading causes of death in adult SLE patients. Advanced age (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 1.03-1.05), treatment with mean dosage of systemic glucocorticoid equivalent to >10 mg/d of prednisolone (HR: 1.71, 95% CI: 1.14-2.57), comorbidities with malignancy (HR: 1.94, 95% CI: 1.22-3.09), chronic kidney disease (HR: 1.86, 95% CI: 1.25-2.77), hypertension (HR: 1.42, 95% CI: 1.01-1.98), and admission due to bacterial pneumonia (HR: 1.92, 95% CI: 1.12-3.31) and sepsis (HR: 2.78, 95% CI: 1.51-5.13) were independent risk factors for mortality in SLE patients. CONCLUSION: SLE patients with advanced age, malignancy, chronic kidney disease, hypertension, treated with a higher average dosage of glucocorticoids, and admission due to bacterial pneumonia and sepsis have an increased risk of mortality.

Thrombotic microangiopathy in systemic lupus erythematosus: a cohort study in North Taiwan.

OBJECTIVES: Thrombotic microangiopathy (TMA) co-existing with SLE is rarely reported. This study aimed to investigate the triggering factors, clinical features and outcomes of SLE patients with TMA in Northern Taiwan. METHODS: Twenty-five TMA cases out of 2461 SLE patients admitted to Taipei Veterans General Hospital, between 2000 and 2010, were enrolled. RESULTS: When TMA occurred, 16 (64.0%) patients had infection; 22 (88.0%) were in an active disease state with a SLEDAI score >10. Among the infection group, 13 (81.3%) had an increase in the SLEDAI score of ≥ 4. We found that older age (≥ 50 years), low platelets (≤ 20,000/nm(3)), presence of infection, acute renal failure (ARF) or four or more TMA features were independent risk factors for persistent haematological abnormalities (P < 0.05); older age (≥ 50 years) and a high reticulocyte index (>2%) were the risk factors for persistent renal function impairment (P < 0.05). The overall mortality rate was 52.0% (13 out of 25); older age (≥ 40 years), low complement value, presence of infection (P < 0.001), two or more infection sources, ARF and four or more TMA features were the statistically significant factors contributing to a higher mortality rate. Patients receiving plasma exchange seven times or more had a significantly higher rate of improvement in renal function and haematological abnormalities. CONCLUSIONS: Our study showed that infection was one of the major triggers for the flare-up of SLE disease activity and occurrence of TMA in SLE. Infection is also a strong risk factor for outcome in SLE patients with TMA. Plasma exchange can be considered as an adjuvant treatment modality.

Hemolytic uremic syndrome with ischemic glomerulonephropathy and obliterative vasculopathy in a systemic sclerosis patient treated with cyclosporine-A.

Hemolytic uremic syndrome (HUS) is not a commonly reported complication in post-transplantation patients treated with cyclosporine-A (CSA), and is extremely rare in systemic sclerosis (SSc) patients treated with this drug. CSA may contribute to the development of chronic ischemic glomerulonephropathy and vasculopathy, features not easily distinguished from SSc-related nephropathy. Here, we describe a 41-year-old Chinese man with diffuse-type SSc treated with CSA who developed thrombocytopenia, acute renal failure and hemolytic anemia and was diagnosed with HUS. Renal function and thrombocytopenia improved gradually after intensive treatment of plasma exchange (PE) and high-dose steroid therapy. After PE, renal biopsy showed ischemic glomerulonephropathy and obliterative vasculopathy. This case illustrates that PE can improve the hematological disorders and characteristic renal changes of HUS in SSc patients treated with CSA. However, this therapy may not be effective in normalizing serum creatinine level in SSc patients once CSA has triggered the normal kidney to develop glomerulonephropathy and vasculopathy with ischemic and sclerotic changes.

Mycobacterium-associated lobular panniculitis, mimicking a rheumatoid nodule in a patient with rheumatoid arthritis.

Mycobacterium-associated lobular panniculitis can mimic a rheumatoid nodule and has been seldom reported in rheumatoid arthritis (RA). We describe a 69-year-old woman with RA who presented initially with fever and an indurated skin lesion on the right thigh. Lobular panniculitis was diagnosed after biopsy and was then treated with prednisolone. After this therapy, pulmonary infiltration developed and was later shown by transbronchial biopsy to be caused by Mycobacterium tuberculosis. The panniculitis skin lesion became smaller after prednisolone therapy and was further improved after antituberculosis drugs were added. Reexamination of the previously biopsied skin tissue disclosed acid-fast bacilli. Reactivation or new infection of M. tuberculosis is a current important issue in RA patients, especially after treatment with disease-modifying anti rheumatic drugs or antitumor necrosis factor agents. Mycobacterium-associated lobular panniculitis should be included in the differential diagnosis of indurated skin disorder in RA patients, and acid-fast staining or polymerase chain reaction examination of tuberculosis should be performed routinely on biopsied skin tissue.

Cytomegaloviral or Pneumocystis Jiroveci Pneumonia Increases Mortality in Systemic Lupus Erythematosus Patients with Pulmonary Hemorrhage: Evidence from Bronchoalveolar Lavage Fluid.

OBJECTIVE: To evaluate the role of cytomegaloviral or Pneumocystis jiroveci pneumonia (CMV/PJP) in systemic lupus erythematosus (SLE) patients with pulmonary hemorrhage (PH). METHODS: We retrospectively examined hospital records for 27 SLE patients with PH who received bronchoalveolar lavage fluid (BALF) analyses. Clinical profile and mortality rates were compared between groups with and without CMV/PJP. Risk factors for PH-related mortality were analyzed. RESULTS: Among 27 SLE patients with PH, 15 had pathogens from BALF samples, and 8 had CMV/PJP. Although CMV/PJP was treated, the RR for 90- and 180-day mortality rates of SLE patients with CMV/PJP were higher than those without these infections (5.94, 95% CI 1.44-24.48; 7.13, 95% CI 1.81-28.06, respectively). Risk factors for 90- and 180-day mortality were presence of CMV/PJP (OR 14.2, 95% CI 1.83-109.9; OR 25.5, 95% CI 2.91-223.3, respectively) and use of pulse methylprednisolone for PH treatment (OR 12.0, 95% CI 1.48-97.2; OR 8.5, 95% CI 1.13-63.9, respectively). Factors increasing the 90-day mortality rate were duration of mechanical ventilation exceeding 14 days (OR 11.1, 95% CI 1.11-112.0) and use of aggressive immunosuppression close to PH onset (OR 7.56, 95% CI 1.09-52.4). Three of the 7 patients receiving aggressive immunosuppression died with the presence of CMV/PJP. CONCLUSION: Owing to the high prevalence of CMV/PJP and its association with mortality, routine BALF analysis is recommended for all suitable SLE patients with PH. Use of aggressive immunosuppression does not benefit SLE patients with opportunistic infections during PH attack.

Behcet's disease with uveitis in Taiwan.

BACKGROUND: Behcet's disease is a multisystemic inflammatory disease which may lead to blindness. The purpose of this study was to describe and compare the clinical features and visual outcome of Behcet's uveitis in Taiwan. METHODS: The medical charts of 227 consecutive patients (414 eyes) with Behcet's uveitis who were seen in the Uveitis Clinic of Taipei Veterans General Hospital were reviewed: 96 patients (group A) between 1984 and 1993 and 131 (group B) between 1994 and 2003. RESULTS: The male-to-female ratio was 1.6. The mean age at the time of uveitis onset was 30.8 years. Males were most affected in the 3rd and 4th decades and females in the 2nd to 5th decades. There were more skin and gastrointestinal lesions in males, and less skin and genital lesions in group B. HLA-B51 antigen was found in 35.7% of patients. Treatment with cyclosporin, azathioprine and methotrexate was more frequent in group B. Uveitis occurred bilaterally in 83.9% of patients. At the first visit, potential visual acuity (VA) was 0.1 or less in 24.7% of eyes in males and 11.4% in females. The mean time from presentation to loss of useful vision (> 0.1) was 51 months in 19.1% of eyes. Kaplan-Meier survival analysis estimated the risks of losing useful vision at 5, 10 and 15 years as being 22.6%, 43.0% and 58.5%, respectively. VA at the first and last visits were better and VA deterioration slower in group B. CONCLUSION: Visual outcome is poorer in males than in females and has improved in the recent decade, but still a significant proportion of patients lose their vision quickly. The number of new patients has not decreased.

Recurrent autoimmune inner ear disease (AIED) and polyarteritis nodosa in a patient with large cell lung carcinoma.

Autoimmune inner ear disease (AIED) is a very rare disorder with distinct clinical features and can occur in patients with malignancy or autoimmune diseases. We report a 72-year-old male patient with polyarteritis nodosa treated continuously for 5 years with aggressive immunosuppressive drugs, including cyclophosphamide, who experienced three episodes of acute hearing loss during treatment. Organic lesions of the external and middle ear were excluded by repeated examinations, and if one subscribes to McCabe's (Ann Otol Rhinol Laryngol 88:585-589, 1979) definition of AIED, this condition must be considered as the likely cause of the hearing loss. During the period of treatment, three episodes of AIED occurred, and eventually, lung cancer developed. From the time relationship and clinical manifestations of neuropathy and livedo reticularis, the first episode of hearing loss was more likely to be related to vasculitis itself, while the third episode may well have been associated with the development of lung cancer given the dramatic improvement in the clinical condition following treatment of the tumor by excision and cancer chemotherapy. Coexistence of AIED, vasculitis, and malignancy in the same patient has only been reported infrequently, and our case suggests that this coexistence may not be coincidental. For those patients with autoimmune disease who are on long-term immunosuppressive drug therapy, active surveillance for a nascent malignant tumor should be exercised if AIED recurs or persists.

Adherence to guidelines in monitoring amiodarone-induced thyroid dysfunction.

RATIONALE, AIMS AND OBJECTIVES: Baseline thyroid function testing and regular follow-up of thyroid function under amiodarone usage was recommended by guidelines. Little is known about the status of amiodarone monitoring in real-world clinical care in Taiwan. The objective was to determine the rate of thyroid monitoring and to assess the clinical and physicians' characteristics associated with adequate monitoring in a tertiary referral centre for arrhythmia. METHODS: We reviewed the medical records of patients receiving amiodarone during the period 2008-2009 at Taipei Veterans General Hospital. The rate of baseline and follow-up thyroid function monitoring during amiodarone therapy were calculated. Factors associated with guideline adherence to monitoring were analysed. RESULTS: Among the 1319 enrolled cases, 36.4% (n = 480) underwent baseline thyroid function testing and 1.1% (n = 15) received measurement of anti-thyroid peroxidase antibody before amiodarone initiation. Regular follow up of thyroid function under amiodarone usage occurred in only 8.6% (n = 114) of cases. Baseline thyroid function was more likely to be present in patients of younger age (P < 0.001), female sex (P = 0.01), and in those who received amiodarone therapy from cardiologists (P < 0.001) or electrophysiologists (P < 0.001) with fewer years of service (P < 0.001). Upon multivariate analysis, only physicians' expertise (cardiologist versus non-cardiologist, OR = 5.67, 95% CI: 2.44-13.16) and years of service (OR = 0.97, 95% CI: 0.95-0.998) were significantly associated with adequate thyroid monitoring. CONCLUSIONS: The rate of thyroid monitoring with amiodarone therapy had been suboptimal. Strategies to enhance guideline adherence are needed.

Pulmonary arterial hypertension in autoimmune diseases: an analysis of 19 cases from a medical center in northern Taiwan.

BACKGROUND AND PURPOSE: Pulmonary arterial hypertension (PAH), a serious complication of autoimmune diseases, has rarely been reported in Taiwan. METHODS: Nineteen patients with various autoimmune diseases diagnosed with PAH at Taipei Veterans General Hospital from 2002 to 2004 were enrolled; the underlying autoimmune diseases included systemic lupus erythematosus (n = 6), primary Sjögren's syndrome (n = 5), systemic sclerosis (n = 4), adult-onset Still's disease (n = 2), and mixed connective tissue disease (n = 2). The characteristic manifestations of underlying autoimmune diseases and the clinical features of PAH were analyzed. RESULTS: There were 16 female and 3 male patients. The median age at onset of PAH was 44 years and the mean right ventricular systolic pressure (RVSP) was 67.9 mm Hg. Patients without pneumonitis had a significantly higher RVSP value than those with pneumonitis (77.5 +/- 24.3 vs 54.8 +/- 18.4 mm Hg, p=0.041). Four out of 7 patients (57.1%) with RVSP >or=80 mm Hg and 1 out of 12 patients (8.3%) with RVSP <80 mm Hg died. In all of the 19 patients, the severity of RVSP was significantly correlated with serum uric acid (UA) level (r = 0.686, p=0.001). Among the PAH patients without pneumonitis, the severity of RVSP inversely correlated with the diffusion capacity of the lung for carbon monoxide (DLCO) [r = -0.856, p=0.003]. The characteristic manifestations of underlying autoimmune diseases included a high incidence of Raynaud's phenomenon (15/19, 78.9%), a high titer of antinuclear antibody (13/17, 76.5%), positive anti-ribonucleoprotein antibody (8/15, 53.3%), hypergammaglobulinemia (15/19, 78.9%), hyperuricemia (13/19, 68.4%), and less renal involvement. CONCLUSIONS: PAH in autoimmune diseases could be potentially fatal with characteristic manifestations. Moreover, RVSP correlated directly with serum UA level and inversely with DLCO.

Conjunctival biopsy in sarcoidosis.

BACKGROUND: Conjunctival biopsy is considered to be a simple, safe and specific diagnostic procedure for sarcoidosis. This study was designed to determine the value of this procedure in Taiwan. METHODS: This study was conducted from December 2003 to April 2005 at the uveitis clinic of Taipei Veterans General Hospital. Blind sampling was conducted, obtaining a biopsy sample measuring 1 cm long by 3 mm wide from both lower fornices. A positive result was defined as the presence of non-caseating granuloma when other granuloma-forming processes had been excluded. RESULTS: Twenty-nine patients (7 men, 22 women) were enrolled. Mean age at diagnosis was 47.8 +/- 12.4 years. The most common initial symptom was eye-related problems in 19 (65.5%) patients. Of 58 biopsies, 15 (25.9%) specimens in 11 (37.9%) patients proved to be positive. Four patients experienced bilateral involvement; 7 patients had unilateral involvement. No prominent conjunctival nodules or follicles were noted. Gender, age, presence of uveitis, initial symptoms, and chest condition comparisons revealed no association between positive and negative conjunctival biopsies. CONCLUSION: Blind and bilateral conjunctival biopsy, due to its ease, safety and specificity, could be the first biopsy inpatients with clinical or chest X-ray abnormalities suggesting sarcoidosis. None of our patients with positive biopsy had nodular lesions.

Acute massive pulmonary hemorrhage after craniotomy in a patient with systemic lupus erythematosus.

Acute massive pulmonary hemorrhage (AMPH) is a rare life-threatening complication of systemic lupus erythematosus (SLE). We report a lupus nephritis patient with active disease, in whom AMPH developed after craniotomy for brain injury. Computed tomography scan of the brain revealed a subdural hemorrhage and intracranial hemorrhage with a midline shift, indicating increased intracranial pressure (IICP). Neurogenic pulmonary edema (NPE) was suspected 5 days after operation due to dyspnea and chest radiograph findings of bilateral infiltrations. Seven days after the craniotomy, she had bloody sputum, a sudden drop in blood hemoglobin level (from 12.3 g/dL to 8.8 g/dL), and diffuse alveolar infiltrates in both lung fields. All of these features were characteristic manifestations of AMPH. Complete blood count disclosed mild thrombocytopenia (88,000/mm3). We believe that in an SLE patient, IICP or NPE might be risk factors in the development of AMPH.

Temporal arteritis.

Temporal arteritis, a chronic inflammatory vasculitis involving medium- and large-sized arteries, has rarely been reported in Asia. However, we report 2 cases, in which the patients initially presented with headache. Physical examination disclosed engorged, hard and palpable vessels in the temporal areas. Temporal-artery biopsy revealed 2 different types of arteritis: the multinucleated giant cell type and the panarteritis type without multinucleated giant cells. One patient was positive for immunoglobulin G anticardiolipin antibody. The pathologic findings of the different subsets of temporal arteritis, and the relationship between anticardiolipin antibody and the extent of vascular complications of temporal arteritis, are discussed.

Laryngotracheal involvement as the initial manifestation of relapsing polychondritis.

Relapsing polychondritis (RP) is a rare multisystemic disease characterized by recurrent inflammation of cartilaginous and noncartilaginous tissues. When laryngotracheal or bronchial cartilages are involved, the disease can be life-threatening and needs aggressive treatment. Upper airway complaints are rare as initial presentations of RP. Here, however, we present a case of RP, with initial manifestations of cough and dyspnea that were treated as bronchial asthma for 6 months. Subglottic stenosis was found in April 2003, during a bronchoscopic examination, and emergency tracheostomy was performed. Auricular and nasal chondritis and bilateral scleritis developed 3 months after tracheostomy. High doses of methylprednisolone and immunosuppressive agents were used, and active inflammation in the eyes and ears was controlled, but the patient's upper airway was completely collapsed. This case is reported with the hope of increasing awareness about the potential for early upper airway involvement in RP.

HLA-DR typing by polymerase chain reaction amplification with sequence-specific primers in paternity disputes.

BACKGROUND: HLA-DR typing was generally performed by serology before. HLA-DRB1 typing can be achieved by polymerase chain reaction amplification with sequence specific primers (PCR-SSP). METHODS: In this study, primers for "low-resolution" HLA-DR typing by PCR-SSP were synthesized upon our request by a company in Taiwan. Twenty-eight DNA samples from international standardized DNA Reference Panel and 20 DNA samples with known serological typing were used as control. We conducted HLA-DR PCR-SSP typing on 18 samples from 6 true paternity trios, 16 samples from 8 true duos, 27 from 9 false trios, and 8 from 4 false duos. These DNAs from disputed paternity families had been previously tested for the parentage using polymerase chain reaction (PCR)-amplified short tandem repeat (STR) analysis. RESULTS: No false positive nor false negative results were obtained in typing 28 positive control DNA samples from international standardized DNA Reference Panel for HLA Class II. Among the 20 DNA samples typed by microlymphocytotoxicity technique, the discordant typing results between HLA-DR PCR-SSP typing and serological typing were found in 3 (15%). In the family of true paternity, HLA-DR typing could not exclude any of alleged fathers and the pattern of inheritance was consistent with autosomal codominant. By HLA-DR typing alone, paternity in 2 alleged fathers out of 9 false trios and 2 alleged fathers out of 4 false duos could not be excluded. CONCLUSIONS: Precise HLA-DR typing can be achieved by PCR-SSP analysis. Economic considerations preclude HLA-DR typing in routine parentage tests where STR typing is performed first.