Intravenous immunoglobulins for steroid‐refractory esophageal involvement related to polymyositis and dermatomyositis: A series of 73 patients

Objective

To assess the long‐term outcome of esophageal complications in the group of patients receiving intravenous immunoglobulins (IVIG) for the treatment of severe steroid‐refractory esophageal involvement related to polymyositis/dermatomyositis (PM/DM).

Methods

We retrospectively reviewed the medical records of 73 patients (39 with PM, 34 with DM) with steroid‐resistant esophageal involvement. Esophageal involvement was evaluated by clinical and manometric investigations.

Results

Seventy‐three patients with steroid‐refractory esophageal involvement related to PM/DM received IVIG therapy (2 gm/kg monthly). The median interval between PM/DM diagnosis and the onset of esophageal complications was 6 months. The most common clinical manifestations revealing esophageal dysfunction were dysphagia (69.9%), coughing while eating (61.6%), and gastroesophageal reflux into the pharynx and/or mouth (34.2%). Twenty‐five patients exhibited life‐threatening esophageal complications requiring exclusive enteral feeding; 33 patients (45.2%) with esophageal impairment developed aspiration pneumonia. Sixty patients (82.2%) exhibited resolution of esophageal clinical manifestations, leading to a return to normal oral feeding and ablation of feeding enteral tubes. Four other patients (5.5%) improved, although they still experienced mild dysphagia intermittently. Because of impaired cricopharyngeal muscle relaxation, another patient successfully underwent cricopharyngeal myotomy. Eight patients died from aspiration pneumonia (n = 6) and cancer (n = 2). Muscle weakness, thoracic myopathy, and aspiration pneumonia were independent predictive factors of IVIG‐treated esophageal complications in PM/DM patients.

Conclusion

Our findings indicate that IVIG should be considered in life‐threatening esophageal impairment complicating steroid‐resistant PM/DM. We also suggest that combined therapy of IVIG and high‐dose steroids may be the first‐line therapy in PM/DM patients with life‐threatening esophageal manifestations.     

Prospective study of high-dose intravenous immunoglobulin for the treatment of steroid-resistant polymyositis and dermatomyositis

Abstract

High-dose intravenous immunoglobulin (IVIG) therapy has been effective in treating many autoimmune and systemic inflammatory diseases. In the present prospective study, we evaluated the efficacy of IVIG for patients with polymyositis (PM) and dermatomyositis (DM) refractory to treatment with high-dose corticosteroids. PM/DM was defined as steroid-resistant when the muscle strength of a patient did not improve despite the administration of more than 50?mg prednisolone per day for more than 4 weeks. A total of 12 patients with biopsy-proven, steroid-resistant PM/DM received one infusion of polyethylene glycol-treated human IgG at a dose of 0.4?g per kg per day for five successive days. Three of the patients received a second infusion. All patients were followed for up to 3 months after the infusion. Finally, 8 patients (6 PM and 2 DM; 5 men and 3 women) aged 29–67 years (mean 48 years) were analyzed. Their clinical response was assessed by changes in (a) subjective signs, i.e., fatigue (visual analog scale, VAS), muscle pain (VAS), activities of daily living (ADL), (b) objective signs, i.e., manual muscle strength (MMT) and serum level of creatine kinase (CK). At 12 weeks after the infusion, the patients showed significant improvement in their scores of muscle strength (from a mean of 67.0 to 81.0) and their ADL scores (from a mean of 27.1 to 39.1). The mean serum CK level decreased significantly from 1287.4 to 612.6?IU/l. In addition, the mean VAS of fatigue decreased significantly from 5.5 to 1.3?cm. The physicians’ assessment showed that 87.5% of patients had improved. The average reduced dose of prednisolone was 47.1?mg/day at 12 weeks after infusion in 7 patients who exhibited improvement. Adverse effects, i.e., asymptomatic myocardial infarction and increased blood urea nitrogen (BUN), were noted with two of the 15 infusion (13%). Overall, IVIG was found to be safe and effective for refractory PM and DM.     

Limited effects of high-dose intravenous immunoglobulin (IVIG) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies

OBJECTIVES: The study was conducted with the aim of achieving an improved understanding of the molecular mechanisms of high-dose intravenous immunoglobulin (IVIG) in inflammatory myopathies by investigating the effects on muscle function and immunological molecules in skeletal muscle of polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM) patients. METHODS: Thirteen treatment-resistant patients, 6 PM, 4 DM, 2 IBM and 1 juvenile DM, were treated with 2 g/kg of IVIG, three times at monthly intervals. Functional Index in Myositis and serum creatinine kinase (CK) levels were determined, and muscle biopsies were performed before treatment and after the third IVIG infusion. Immunological molecules were also studied in biopsies taken 24-48 h after the first infusion. RESULTS: Improved muscle function was observed in three patients (1 PM, 1 DM and 1 IBM) and CK levels decreased in five. T cells, macrophages, major histocompatibility complex (MHC) class I antigen on muscle fibres, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression and membranolytic attack complex (MAC) deposits on capillaries were present to an equal degree in biopsies before and after IVIG treatment. No correlation between the clinical response and molecular changes was found. CONCLUSIONS: The clinical effects of high-dose IVIG on muscle function in patients with refractory inflammatory active myositis did not correspond to effects on any of the investigated molecules in our study. T cells, macrophages, phenotypical changes in muscle fibres and endothelial cell activation were still present after treatment. These observations question a role for IVIG as an immune-modulating therapy in patients with inflammatory myopathies.     

Intravenous immunoglobulin therapy in adult patients with polymyositis/dermatomyositis: a systematic literature review

The objectives of this study are to review and summarize published information on the use, effectiveness, and adverse effects of intravenous immunoglobulin (IVIG) in patients with polymyositis (PM) or dermatomyositis (DM) and to search MEDLINE and CNKI (Chinese) databases from 1985 to 2011 to retrieve clinical research articles concerning IVIG in adult patients with PM/DM. Of the 14 articles selected, two were randomized controlled trials, nine prospective open studies, and three retrospective studies with a total of 308 adult patients. IVIG has been used successfully in the treatment of PM/DM. The standard dose is 2 g/kg, given in two to five individual daily doses. The course of IVIG treatment is usually 3~6 months. IVIG therapy seemed rarely employed as first-line therapy in PM/DM. In a double-blind study conducted in patients with refractory DM, IVIG combined with corticosteroid significantly improved muscle strength and decreased serum creatine kinase level, compared with placebo. The beneficial effect of IVIG in refractory, flare-up, rapidly progressive, or severe PM/DM has been documented in many open-label trials. IVIG was shown to be effective in most of PM/DM patients with lung involvement and esophageal involvement. In some patients, IVIG can lower the corticosteroid dose required for maintenance, demonstrating the most effective steroid-sparing effect. Adverse effects were generally tolerable. IVIG is effective in the treatment of adult patients with PM/DM and appears to be relatively well tolerated and safe. IVIG may be a good choice especially in patients with refractory, flare-up, rapidly progressive, or severe PM/DM, and can be tried in patients with a contraindication for corticosteroid.     

Efficacy of high-dose intravenous immunoglobulin therapy in Japanese patients with steroid-resistant polymyositis and dermatomyositis

Abstract

Intravenous immunoglobulin (IVIG) therapy was administered to 15 patients who were refractory to traditional steroid therapy [eight with polymyosis (PM), seven with dermamyosis (DM)] to evaluate its efficacy. Serum creatine kinase (CK) significantly decreased from week 1, and manual muscle test scores (MMT) and activities of daily living (ADL) significantly increased from week 2. Efficacy rates were 93.3% (14/15 patients) as assessed using the MMT score, 80.0% (12/15 patients) using the ADL score, and 100% (15/15 patients) using the serum CK level. When changes in the serum CK level over two four-week periods, one before IVIG therapy (from week ?4 to week 0) and one after IVIG therapy (from week 0 to week 4), were transformed to natural logarithms, the four-week change after IVIG therapy was significantly greater than that before IVIG therapy. The estimated duration of the serum CK level remaining normal in 50% of the patients after IVIG therapy was 334.5 days. Adverse reactions were observed in seven of 16 patients (43.8%) during the study period, but none of the adverse reactions were considered to be serious or required emergency treatment. In conclusion, the present study indicates that IVIG therapy is effective for steroid-resistant PM/DM.     

Efficacy of high-dose intravenous immunoglobulin therapy in Japanese patients with steroid-resistant polymyositis and dermatomyositis

Intravenous immunoglobulin (IVIG) therapy was administered to 15 patients who were refractory to traditional steroid therapy [eight with polymyosis (PM), seven with dermamyosis (DM)] to evaluate its efficacy. Serum creatine kinase (CK) significantly decreased from week 1, and manual muscle test scores (MMT) and activities of daily living (ADL) significantly increased from week 2. Efficacy rates were 93.3% (14/15 patients) as assessed using the MMT score, 80.0% (12/15 patients) using the ADL score, and 100% (15/15 patients) using the serum CK level. When changes in the serum CK level over two four-week periods, one before IVIG therapy (from week −4 to week 0) and one after IVIG therapy (from week 0 to week 4), were transformed to natural logarithms, the four-week change after IVIG therapy was significantly greater than that before IVIG therapy. The estimated duration of the serum CK level remaining normal in 50% of the patients after IVIG therapy was 334.5 days. Adverse reactions were observed in seven of 16 patients (43.8%) during the study period, but none of the adverse reactions were considered to be serious or required emergency treatment. In conclusion, the present study indicates that IVIG therapy is effective for steroid-resistant PM/DM. An erratum to this article can be found at     

Prospective study of high-dose intravenous immunoglobulin for the treatment of steroid-resistant polymyositis and dermatomyositis

High-dose intravenous immunoglobulin (IVIG) therapy has been effective in treating many autoimmune and systemic inflammatory diseases. In the present prospective study, we evaluated the efficacy of IVIG for patients with polymyositis (PM) and dermatomyositis (DM) refractory to treatment with high-dose corticosteroids. PM/DM was defined as steroid-resistant when the muscle strength of a patient did not improve despite the administration of more than 50mg prednisolone per day for more than 4 weeks. A total of 12 patients with biopsy-proven, steroid-resistant PM/DM received one infusion of polyethylene glycol-treated human IgG at a dose of 0.4g per kg per day for five successive days. Three of the patients received a second infusion. All patients were followed for up to 3 months after the infusion. Finally, 8 patients (6 PM and 2 DM; 5 men and 3 women) aged 29–67 years (mean 48 years) were analyzed. Their clinical response was assessed by changes in (a) subjective signs, i.e., fatigue (visual analog scale, VAS), muscle pain (VAS), activities of daily living (ADL), (b) objective signs, i.e., manual muscle strength (MMT) and serum level of creatine kinase (CK). At 12 weeks after the infusion, the patients showed significant improvement in their scores of muscle strength (from a mean of 67.0 to 81.0) and their ADL scores (from a mean of 27.1 to 39.1). The mean serum CK level decreased significantly from 1287.4 to 612.6IU/l. In addition, the mean VAS of fatigue decreased significantly from 5.5 to 1.3cm. The physicians assessment showed that 87.5% of patients had improved. The average reduced dose of prednisolone was 47.1mg/day at 12 weeks after infusion in 7 patients who exhibited improvement. Adverse effects, i.e., asymptomatic myocardial infarction and increased blood urea nitrogen (BUN), were noted with two of the 15 infusion (13%). Overall, IVIG was found to be safe and effective for refractory PM and DM.     

CD8-positive T cell-induced liver damage was found in a patient with polymyositis

We describe a case of polymyositis (PM) with liver injury that occurred in a patient with rheumatoid arthritis (RA). A 74-year-old woman who had a 12-year history of RA was admitted to our hospital because of muscle weakness and liver dysfunction. CD8-positive T cell infiltration was found in the interstitium of both the liver and muscle. In addition to the administration of a large amount of prednisolone (PSL), high-dose intravenous immunoglobulin (IVIG) successfully improved myositis and hepatitis. Our case indicates the pathogenic potential of CD8-positive T cells in PM-associated liver injury.     

Intravenous immunoglobulins as treatment of life threatening esophageal involvement in polymyositis and dermatomyositis

Esophageal involvement is considered a major cause of morbidity and an indicator of poor prognosis in polymyositis (PM) and dermatomyositis (DM). We describe 3 patients with steroid resistant PM/DM with life threatening esophageal involvement, resulting in impossible oral feeding and enteral nutrition with a gastric tube. All patients had both dramatic and rapid improvement of all clinical manifestations after initiation of intravenous immunoglobulin (IVIG) therapy. Swallowing disorders completely disappeared after the second infusion of IVIG, which permitted normal oral feeding and ablation of the gastric tube. Our findings suggest IVIG should be considered the treatment of choice in such cases.     

Intravenous immunoglobulin treatment for pregnancy-associated dermatomyositis

Pregnancy-associated dermatomyositis (DM) is a rare disorder, until recently treated only with corticosteroids due to the toxicity of other immunosuppressive agents for the fetus. We present a pregnant woman with DM treated successfully with intravenous immunoglobulin (IVIG) and medium dose corticosteroids. A 42-year-old woman presented with a rash, muscle weakness and increased muscle enzymes on the 15th week of her first pregnancy. After the diagnosis of DM she was treated with the combination of medium dose corticosteroids and IVIG. The patients’ symptoms resolved rapidly. No complications were noted for either her or the fetus. Both she and her son remain disease-free after 6 years follow-up. In conclusion, IVIG treatment is a safe and effective alternative for pregnancy-associated DM.     

Effects of intravenous immunoglobulin therapy in Japanese patients with polymyositis and dermatomyositis resistant to corticosteroids: a randomized double-blind placebo-controlled trial

High-dose intravenous immunoglobulin (IVIG) therapy has been effective in treating various autoimmune and systemic inflammatory diseases. Here, we assessed the efficacy and safety of IVIG therapy with polyethylene glycol-treated human IgG (drug code GB-0998) for patients with corticosteroid-refractory polymyositis (PM) and dermatomyositis (DM) by means of a randomized, double-blind, placebo-controlled study. We randomly assigned 26 subjects (16 PM and 10 DM) to receive either GB-0998 or placebo. Intragroup comparison in the GB-0998 group showed statistically significant improvements due to GB-0998 administration in the primary endpoint (manual muscle test score) and secondary endpoints (serum creatine kinase level and activities of daily living score). However, significant improvements were also found in the placebo group, and comparison of the GB-0998 group with the placebo group did not show any significant difference between the groups. We discuss possible reasons for the absence of a clear intergroup difference in efficacy. Nineteen adverse drug reactions were observed in 11 of 26 subjects (42.3%), of which 2 events (decreased muscle strength and increased serum creatine kinase) were assessed as serious; however, they are previously known events. These results indicate that GB-0998 can be safely used with the same precautions as other current IVIG therapy.     

Chronological evaluation of the onset of histologically confirmed interstitial pneumonia associated with polymyositis/dermatomyositis

OBJECTIVE: The present study was designed to determine the chronological sequence of interstitial pneumonia, skin involvement, and muscle involvement associated with polymyositis/dermatomyositis (PM/DM). METHODS: We examined our own cases of histologically confirmed interstitial pneumonia associated with PM/DM. In addition, a review of the literature was done to evaluate other cases of histologically confirmed interstitial pneumonia associated with PM/DM. Lung involvement was the first clinical symptom for all of our 8 patients. RESULTS: Including the literature review and our 8 cases, there were 94 patients with PM/DM in whom interstitial pneumonia was histologically confirmed (36 PM, 50 DM, and 8 amyopathic DM). Chronological evaluation between the diagnosis of PM/DM and lung involvement demonstrated that most lung involvement occurred just before or just after the diagnosis of PM/DM. Interstitial pneumonia was preceded in 35 of 87 evaluable patients [21 cases with PM (61.8%), 14 cases with DM and amyopathic DM (40.2%)]. In 60 of 87 evaluable patients (69.0%), lung involvement occurred as a clinical manifestation at the diagnosis of PM/DM. CONCLUSION: The present data demonstrate that interstitial pneumonia was frequently the initial onset in patients with PM/DM.     

Effects of intravenous immunoglobulin therapy in Japanese patients with polymyositis and dermatomyositis resistant to corticosteroids: a randomized double-blind placebo-controlled trial

Abstract

High-dose intravenous immunoglobulin (IVIG) therapy has been effective in treating various autoimmune and systemic inflammatory diseases. Here, we assessed the efficacy and safety of IVIG therapy with polyethylene glycol-treated human IgG (drug code GB-0998) for patients with corticosteroid-refractory polymyositis (PM) and dermatomyositis (DM) by means of a randomized, double-blind, placebo-controlled study. We randomly assigned 26 subjects (16 PM and 10 DM) to receive either GB-0998 or placebo. Intragroup comparison in the GB-0998 group showed statistically significant improvements due to GB-0998 administration in the primary endpoint (manual muscle test score) and secondary endpoints (serum creatine kinase level and activities of daily living score). However, significant improvements were also found in the placebo group, and comparison of the GB-0998 group with the placebo group did not show any significant difference between the groups. We discuss possible reasons for the absence of a clear intergroup difference in efficacy. Nineteen adverse drug reactions were observed in 11 of 26 subjects (42.3%), of which 2 events (decreased muscle strength and increased serum creatine kinase) were assessed as serious; however, they are previously known events. These results indicate that GB-0998 can be safely used with the same precautions as other current IVIG therapy.     

Progression of interstitial lung disease upon overlapping of systemic sclerosis with polymyositis

We describe a 73-year-old woman with systemic sclerosis (SSc)-polymyositis (PM) overlap syndrome, primarily SSc followed by PM. She had suffered from SSc and had interstitial pneumonia (IP), which was stable. Eight years after the initial diagnosis of SSc, proximal muscle weakness, myalgia, and dyspnea on effort developed. A chest computed tomography (CT) showed reticular shadows, and serum markers of IP such as KL-6 and surfactant protein-D were elevated at 1,170 U/mL and 176 ng/mL, respectively. Bronchoalveolar lavage fluid showed a remarkably increased number of lymphocytes. Exacerbation of SSc-IP 8 years after the initial diagnosis of SSc is not usual, and a marked increase in the number of lymphocytes in bronchoalveolar lavage fluid is also uncommon in SSc-IP, indicating overlap of another connective tissue disease. The diagnostic criteria for PM were satisfied; thus, SSc-PM overlap syndrome was diagnosed. We emphasize the need to investigate whether another connective tissue disease has developed when symptoms or laboratory findings cannot be explained by the usual clinical course of an existing connective tissue disease.     

Results and long-term followup of intravenous immunoglobulin infusions in chronic, refractory polymyositis: an open study with thirty-five adult patients

OBJECTIVE: Polymyositis is a rare inflammatory muscular disease of unknown cause. Corticosteroids and immunosuppressive drugs are the first choice of therapy but are not always effective and may cause serious side effects. Many studies have shown that polyvalent intravenous immunoglobulin (IVIG) may be of interest for the treatment of dermatomyositis. We carried out an open, prospective study to evaluate the efficacy of IVIG in subjects with polymyositis that was refractory to traditional treatments, and we evaluated the benefits of this therapy over a long-term period of followup. METHODS: Thirty-five adult white patients (20 female, 15 male, mean age 43.5 years [SD 16.8]) with chronic, refractory polymyositis were treated with high doses of IVIG, after the patients had received the following traditional treatments: prednisone (n = 35), methotrexate (n = 24), azathioprine (n = 13), cyclophosphamide (n = 4), cyclosporine (n = 7), chlorambucil (n = 1), plasmapheresis (n = 8), lymphopheresis (n = 1), and total body irradiation (n = 1). There had been no changes in the patients' treatment in the 2 months before the initiation of IVIG therapy, and doses were not increased during IVIG treatment. We used preparations of polyvalent human IVIG with increased concentrations of intact IgG. The patients received 1 gm/kg/day for 2 consecutive days per month. The mean course of treatment was 4-6 months. The clinical assessment involved the evaluation of proximal muscle power, muscle disability scale score, and esophageal disorders. The biochemical evaluations carried out before each treatment period were compared by Student's t-test and nonparametric Wilcoxon test. Results were considered to be significant at P = 0.05. RESULTS: In the short-term, significant clinical improvement was noted in 25 of the 35 patients (71.4%). Mean muscle power was estimated before and after IVIG therapy and was found to be significantly improved (P < 0.01). All patients had a significant biochemical response. Mean creatine kinase levels during IVIG therapy decreased significantly before the fourth IVIG perfusion (P < 0.01). Side effects, usually minor, were noted in 6 patients. This benefit allowed the initial prednisone dose to be reduced by >50% in all patients. The mean (+/- SD) followup time for the 25 patients who responded favorably to IVIG treatment was 51.4 +/- 13.1 months. Twelve of these 25 patients remained in full remission following their initial course of IVIG, resulting in complete stoppage of medication in 5 patients or low doses of steroids in 7 patients. The condition of 6 patients remained improved and no other drugs were prescribed, but the patients remained dependent on IVIG infusions. Seven of the 25 patients who responded well to IVIG treatment relapsed at an average of 17.1 months (range 4-23 months) after the discontinuation of IVIG. CONCLUSION: IVIG is an interesting therapy for the treatment of polymyositis, with results showing that the condition of approximately 70% of the patients tested improved. After the discontinuation of the IVIG therapy, the efficacy remained stable in 50% of the patients, with a followup of over 3 years.     

Two cases of interstitial pneumonia with anti-Jo-1 antibodies in the absence of myositis]

We present two cases of interstitial pneumonia with anti-Jo-1 antibodies in the absence of myositis. The first patient was a 38-year-old woman and the second, a 59-year-old woman. Both patients were admitted to our hospital complaining of dry cough and dyspnea on effort. The diagnosis of interstitial pneumonia was made from chest radiography, computed tomography and surgical lung biopsy. Anti-Jo-1 antibodies, which were highly specific for polymyositis and dermatomyositis (PM/DM), were detected in both patients. However, the serum creatine kinase concentrations and electromyographic findings in both patients were normal, and no clinical signs (including muscle weakness, rash and arthralgia) were found. In the first patient, oral prednisolone (PSL) treatment (20 mg day) improved the interstitial pneumonia, but PSL has now been tapered to 17.5 mg day. In the second patient, oral PSL treatment (40 mg day) improved interstitial pneumonia, and the dose was tapered to 5 mg day. The second patient was followed for more than 10 years after treatment, but she has never shown any signs of clinical myositis. Further investigation will be required, because no pathophysiological relation between anti-Jo-1 antibodies and interstitial pneumonia with PM DM has yet been established.     

Intravenous Immunoglobulin Therapy for Refractory Interstitial Lung Disease Associated with Polymyositis/Dermatomyositis

Interstitial lung disease (ILD) associated with polymyositis/dermatomyositis (ILD-PM/DM), including amyopathic dermatomyositis (ADM), is recognized as an important condition because it frequently causes death, despite intensive therapy with high-dose corticosteroid and immunosuppressive agents, such as cyclosporine A and cyclophosphamide. Intravenous immunoglobulin therapy (IVIG) has shown efficacy for myopathy associated with PM/DM, but its usefulness for ILD-PM/DM is unclear. This study was designed to investigate the efficacy of IVIG for refractory ILD-PM/DM. A review was made of medical charts of five patients (2 men and 3 women) who were treated with IVIG for refractory ILD-PM/DM resistant to high-dose corticosteroid and cyclosporine A and/or cyclophosphamide. One patient had acute ILD-PM and four patients had acute ILD-ADM. Of the five patients, one patient with ILD-PM and one patient with ILD-ADM survived. No adverse reactions were seen due to IVIG treatment. There were no critical differences in the clinical parameters and clinical courses between survivors and nonsurvivors. IVIG treatment is safe and could be an effective salvage therapy for refractory ILD-PM/DM in certain cases, suggesting that further controlled trials are worthwhile.     

Elevation of cytokeratin 19 fragment in patients with interstitial pneumonia associated with polymyositis/dermatomyositis.

OBJECTIVE: Cytokeratin 19 fragment (CK19) levels in serum have been documented as a useful tumor marker for lung cancer. We hypothesize that CK19 may increase in serum in patients with interstitial pneumonia associated with polymyositis/dermatomyositis (PM/DM) and CK19 might be a useful variable to evaluate the activity of lung injury. METHODS: 1. We measured CK19 in sera in 15 patients diagnosed with PM/DM; 6 had nonspecific interstitial pneumonia (NIP), 4 had acute interstitial pneumonia (AIP), and 5 had no pulmonary involvement. We also measured CK19 in 10 healthy nonsmokers serving as a control group. 2. We evaluated the correlation between CK19 level and individual clinical course in patients with pulmonary involvement associated with PM/DM. RESULTS: CK19 levels in sera of patients with NIP associated with PM/DM were significantly higher versus patients with PM/DM without interstitial pneumonia and healthy nonsmokers. CK19 levels in sera in patients with AIP associated with PM/DM were significantly higher compared with the other groups. CK19 values in sera changed according to the progression or improvement of interstitial pneumonia. Immunohistochemical studies using pulmonary tissues obtained at autopsy from patients with AIP associated with PM/DM revealed that the hyaline membrane was mostly stained by anti-human cytokeratin 19 monoclonal antibody as well as the strong positivity of proliferating type II pneumocytes. CONCLUSION: These results suggest that the measurement of CK19 was a useful variable to evaluate the activity of lung injury in interstitial pneumonia associated with PM/DM.     

Relapsing pure red cell aplasia associated with B-cell chronic lymphocytic leukemia successfully treated by intravenous immunoglobulin concentrate

Pure red cell aplasia (PRCA) is a rare syndrome characterized by a normochromic normocytic anemia and the absence of mature erythroid precursors in an otherwise normocellular bone marrow. Acquired PRCA has been associated with autoimmune, viral or neoplastic conditions. We report the case of a patient with B-cell chronic lymphocytic leukemia (B-CLL) and PRCA. Conventional antileukemic treatment had no effect on the PRCA, while the B-CLL showed partial remission according to the International Workshop on Chronic Lymphocytic Leukemia response criteria. The patient was treated with cyclosporin A that resulted in complete response of the PRCA lasting 12 months. PRCA relapse, suggested by a hemoglobin decrease and by bone marrow biopsy, did not respond to prednisone and cyclophosphamide treatment. Fludarabine treatment was started in July 1999; the B-CLL remained stable according to the International Workshop on Chronic Lymphocytic Leukemia response criteria, the PRCA did not improve. In October 1999, because of intercurrent pneumonia, the patient was treated with intravenous immunoglobulin (IVIG) concentrate. This treatment resulted in total resolution of the pneumonia and a complete response of the PRCA. Therefore the patient remained on monthly IVIG. In view of the known efficacy of IVIG in the treatment of PRCA induced by parvovirus B19 and since serial polymerase chain reaction determinations of parvovirus B19 were repeatedly negative in our subject, we hypothesize that the IVIG per se may have a therapeutic effect on PRCA. The present case suggests that IVIG may be of benefit for PRCA patients even if the disease is unrelated to parvovirus B19 infection.     

Schwere Dysphagie und flammende Hautrötung bei einem 59-jährigen Patienten

A 59-year-old man presented with a history of dysphagia and generalized myalgia and muscle weakness and a rash on the face, neck, and upper arms. Serum muscle enzymes, myoglobin, C-reactive protein, and erythrocyte sedimentation rate were elevated and antinuclear antibodies positive. Electromyographic conduction studies showed pathological changes on arm and leg muscles and magnetic resonance imaging of the oral and neck muscles. A diagnosis of dermatomyositis with severe esophageal involvement was established. Treatment with prednisolone was started and methotrexate added. Enteral feeding with a percutaneous endoscopic gastrostomy was started and a therapy with intravenous immunoglobulin (IVIG) initiated, which caused a rapid improvement of the patient’s ability to swallow. This case demonstrates a patient with polymyositis/dermatomyositis who showed steroid-resistent life-threatening esophageal impairment. IVIG resulted in a dramatic improvement of symptoms.