Rapid and Persistent Reduction of Proteinuria Following Plasma Exchange in a Case of Steroid‐Resistant Focal Segmental Glomerulosclerosis

Abstract: We report on the case of a 45 year old male with focal segmental glomerulosclerosis (FSGS) in whom steroid‐resistant proteinuria was reduced rapidly by plasma exchange. In 1994, he was admitted to our hospital because of massive proteinuria of several years' duration. Renal biopsy confirmed the diagnosis of FSGS. Proteinuria was suppressed partially with the use of dipyridamole. Though oral prednisolone (PSL, 30 mg/day) was effective initially, relapse occurred during PSL tapering. Doses of PSL up to 30 mg/day or additional mizoribine were ineffective. The patient was readmitted for a trial of plasma exchange in April 2000. Four sessions of plasma exchange with albumin replacement over 2 weeks immediately reduced the proteinuria from 3.2 g/day to 0.6 g/day without any change in medication. After discharge, proteinuria remained suppressed for more than 6 months despite a reduction of PSL dose to 15 mg. The rapid and long lasting effect of plasma exchange in the present case argues for the role of a putative circulatory factor in the pathogenesis of proteinuria in FSGS.     

Successful treatment of anti-erythropoietin antibody-mediated pure red cell aplasia with low-dose prednisolone

The standard therapy for anti-erythropoietin (EPO) antibody-mediated pure red cell aplasia (PRCA) is cyclosporine (CyA) or prednisolone (PSL) 0.5–1.0 mg/kg. However, many patients with severe chronic kidney disease (CKD) and chronic heart failure cannot tolerate such an immunosuppressive regimen. An 86-year-old man with anemia related to CKD and chronic heart failure, who had received recombinant human erythropoietin subcutaneously, developed anti-EPO antibody-mediated PRCA. The patient was treated with CyA followed by PSL (1.0 mg/kg); however, he was unable to tolerate this drug regimen. The PSL dose was reduced to 0.2 mg/kg. Surprisingly, his reticulocyte count increased 3 months later, and RBC transfusion was no longer required. Low-dose PSL is a treatment option for patients with anti-EPO antibody-mediated PRCA who cannot tolerate CyA and PSL (0.5–1.0 mg/kg).     

A case of ANCA-negative renal small-vessel vasculitis with tubulointerstitial infiltration of IgG4-positive plasma cells

A 62-year-old male patient presented with progressive renal dysfunction for 2 months. He had elevated serum C-reactive protein and IgG4 levels with absence of anti-neutrophil cytoplasmic antibodies. A renal biopsy showed severe tubulointerstitial nephritis (TIN) with extensive infiltration of IgG4-positive plasma cells, suggesting a diagnosis of IgG4-related kidney disease (IgG4-RKD). However, the identification of a few crescentic glomeruli and necrotizing vasculitis of an interlobular artery lead to a diagnosis of renal small-vessel vasculitis. This case indicates that a careful examination is required to distinguish between IgG4-RKD and TIN caused by renal small-vessel vasculitis.     

Cryofibrinogenemia associated with Sjögren's syndrome: a case of successful treatment with high-dose corticosteroid

Cryofibrinogenemia (CF) has not been often reported as a complication of various rheumatic diseases. We describe a 44-year-old woman with CF associated with Sj?gren's syndrome (SS), who developed digital necrotic ulcerations and purpura of the lower legs. Cryoprecipitate was detected in her plasma, and immunoelectrophoresis showed that the cryoprecipitate was cryofibrinogen. Alprostadil was intravenously administered, but the ulceration was aggravated. Subsequently, administration of high-dose prednisolone (PSL) at 60 mg/day was started, and the ulceration remarkably improved. Cryofibrinogen, detected before the administration of high-dose PSL, was negative after PSL. This is the first case presentation of CF associated with SS successfully treated with high-dose corticosteroid.     

Successful treatment with bortezomib for a patient with plasma cell leukemia accompanied by severe hyperbilirubinemia

A 59-year-old woman was admitted to our hospital with jaundice, renal dysfunction, anemia and hypercalcemia. Primary plasma cell leukemia (PCL) was diagnosed based on findings of IgA-λ type M-protein, 22% plasma cells in the bone marrow and 23.1% plasma cells of WBC in the peripheral blood. Because the total bilirubin (T.Bil) level increased even after the administration of prednisolone (PSL), dexamethasone and methylprednisolone, the patient was started on bortezomib (0.7 mg/m(2) on days 1, 4, 8 and 11 for 3 weeks) combined with PSL (40 mg/day). The level of T.Bil decreased and the patient's condition remarkably improved. We then increased the dose of bortezomib to 1.0 mg/m(2) in the second course, but discontinued treatment just after starting the third course because NCI-CTCAE Grade 3 peripheral neuropathy developed. According to the criteria of the International Myeloma Working Group, the response category was VGPR (=very good partial response) at 1 month after pausing treatment. We recommend these novel agents for PCL, which is an aggressive form of extramedullary plasma cell cancer.     

Successful Treatment of Mepolizumab- and Prednisolone-resistant Allergic Bronchopulmonary Aspergillosis with Dupilumab

A 45-year-old man with allergic bronchopulmonary aspergillosis (ABPA) was treated with oral prednisolone (PSL) (30 mg/day), inhaled corticosteroids, and long-acting beta2-agonists. After confirmation of a PSL-dependent status (8 mg/day), subcutaneous injection with anti-interleukin (IL)-5 antibody (mepolizumab, 100 mg/month) was performed, and the PSL dose was tapered to 5 mg/day. However, ABPA recurred and proved refractory to oral itraconazole (200 mg/day). Alternative subcutaneous injection therapy with dupilumab (induction dose of 600 mg followed by a maintenance dose of 300 mg/2 weeks) enabled the successful withdrawal of oral PSL without clinical deterioration. This case demonstrates the potential utility of dupilumab for steroid-dependent ABPA via the synergistic suppression of IL-4 and IL-13 compared to monotherapy with anti-IL-5 antibody.     

Transient hypofibrinogenemia induced by prednisolone in a case of acute lymphoblastic leukemia

We report here a patient with acute lymphoblastic leukemia (ALL) in whom hypofibrinogenemia developed during chemotherapy. The patient was a 65-year-old female who was diagnosed as having common ALL, and she was treated with BHAC-DMPV (enocitabine: 160 mg, daunorubicin : 40 mg, 6-MP: 35 mg, prednisolone (PSL): 60 mg, and vincristine: 2 mg). Hypofibrinogenemia appeared promptly each chemotherapy, including PSL was given. To ascertain a correlation between hypofibrinogenemia and the drugs given in this patient, a trial administration of PSL was attempted during a complete remission state. The level of fibrinogen, in terms of the amount of antigen or coagulability, decreased during PSL treatment, although the levels of AT III, plasminogen, alpha 2PI.Plm complex, and FDP did not change. Thus, it is difficult to speculate that PSL induced destruction of leukemia cells and release of protease from the cells resulting in fibrinolysis and hypofibrinogenemia in this case. These findings also suggest that the administration of only PSL could induce hypofibrinogenemia.     

Etoposide ameliorated refractory hemophagocytic syndrome in a patient with systemic sclerosis]

We successfully treated a 33-year-old woman with etoposide who developed systemic sclerosis (SSc)-associated refractory hemophagocytic syndrome (HPS). She had been diagnosed as SSc because she had had Raynaud's phenomenon, proximal scleroderma, telangiectasia, microstomia, thickening and shortening of lingual frenulum and positive antinuclear antibody since 1994. In September 1999, she showed high fever, anemia, thrombocytopenia, elevation of serum lactate dehydrogenase (LDH) and ferritin levels and hemophagocytosis in her bone marrow, which led to the diagnosis of HPS. Her symptoms were improved by 40 mg of daily oral prednisolone (PSL). While tapering PSL, she complained right coxalgia and magnetic resonance image (MRI) depicted avascular necrosis (AVN) of right femoral head. In May 2000, she again suffered from HPS when she was taking 19 mg of PSL daily. To avoid the development of another AVN of her bone, she was treated with monthly cyclophosphamide (CPA) pulse therapy (300-400 mg/day). Although her HPS transiently ameliorated with CPA, it flared up again with high fever, general fatigue, severe pancytopenia and extremely high serum LDH and ferritin levels after the 4th CPA pulse therapy. She was admitted again to our hospital and PSL was increased to 40 mg daily which did not improve HPS. We, therefore, treated her with intravenous etoposide (100 mg/day, three consecutive days) along with granulocyte-colony stimulating factor (G-CSF). She developed transient bone marrow suppression, but her laboratory data gradually normalized within two weeks and she became afebrile after 18 days of etoposide administration. This is the first case in the literature which suggests the efficacy of etoposide against refractory autoimmune-associated hemophagocytic syndrome.     

A case of refractory Wegener's granulomatosis successfully treated with high-dose methotrexate]

We report a case of generalized Wegener's granulomatosis (WG) successfully treated with high-dose methotrexate (MTX) and predonisolone (PSL). A 35 year-old men had complaints of auditory disturbance and nasal hemorrhage. Diagnosis of WG was made based on positive proteinase-3 anti-neutrophil cytoplasmic antibody (PR3-ANCA), lung nodules, and focal necrotizing glomerulonephritis revealed by renal biopsy. Treatment with cyclophosphamide (CY) and PSL for 3 months was ineffective for the lung nodules. Then, CY was changed to high dose MTX (18mg/week), and his lung lesions improved. In Japan, it is unusual to treat WG with high-dose MTX, but this treatment may be useful in CY-resistant WG.     

Improvement of the maintenance therapy after methylprednisolone pulse therapy--effect of prednisolone combined with immunosuppressants]

OBJECTIVES: We investigated the effect of the combination therapy of prednisolone (PSL) and immunosuppressants after methylprednisolone pulse therapy. METHODS: A protocol of PSL (15-20 mg/day) and mizoribine (150-200 mg/day) after methylprednisolone (mPSL) pulses was used for 2 years to treat 7 patients (PSL + MZB group). Cyclophosphamide (CYC) pulse therapy was added to the combined therapy in 4 patients with severe lupus nephritis. The total dose of predinisolone, and side effects were compared with those in 6 patients who were treated with PSL (30 mg/kg) alone after mPSL pulse therapy (PSL group). RESULTS: No relapses occurred in the PSL + MZB group, although all of 6 patients relapsed in the PSL Group. The total doses of PSL in the PSL + MZB group was about 70% of the PSL Group. There were two patients with Herpes-Zoster infection and one patient with liver dysfunction as side effects, with no differences in the frequency of side effects between the was groups. CONCLUSIONS: Combination maintenance therapy with prednisolone and immunosuppressants after methylprednisolone pulse therapy was effective in preventing relapse.     

Two Cases of Autoimmune Neutropenia Complicated with Other Lineages of Autoimmune Cytopenia,Successfully Treated with Prednisolone

Though adult-onset primary autoimmune pancytopenia (AIP) rarely follows a self-limited course, a standard treatment strategy has not yet been established. We herein report two cases, each involving primary autoimmune neutropenia complicated with autoimmune thrombocytopenia or Evans syndrome. They were refractory to granulocyte-colony stimulating factor, but all lineages of cytopenia promptly recovered with prednisolone (PSL). In case 1, PSL was tapered and discontinued six months after its initiation without AIP relapse. In case 2, PSL has been tapered for five months without relapse. To establish an optimal treatment strategy for AIP, it is necessary to accumulate more cases.     

Lambert-Eaton myasthenic syndrome associated with idiopathic thrombocytopenic purpura and diffuse panbronchiolitis: long-term remission after a course of intravenous immunoglobulin combined with low-dose prednisolone.

We report a case of Lambert-Eaton myasthenic syndrome (LEMS) associated with idiopathic thrombocytopenic purpura (ITP) and diffuse panbronchiolitis (DPB). An extensive search for malignancy yielded negative results. Interestingly, ITP and DPB developed simultaneously when the patient suffered from myasthenic symptoms. This is the first report in the Japanese or English literature of an association of LEMS, ITP, and DPB. The use of cholinesterase blocker alone did not improve the myasthenic symptoms, and the symptoms and signs relapsed with the tapering of prednisolone (PSL) dosage. However, after administration of immunoglobulin (IVIG) (0.4 g/kg/day x 5 days), low-dose PSL (20 mg/day) alleviated the LEMS and ITP, and the diseases have remained in remission for 8 months without additional IVIG. We suspect that there is a synergistic relationship between IVIG and PSL.     

A case of gold lung with positive lymphocyte stimulation test to gold, using bronchoalveolar lymphocytes]

Gold lung, a gold-induced pneumonitis, is considered to be caused by hypersensitivity reaction to gold. We performed lymphocyte stimulation test (LST) to determine the response to gold, using lymphocytes obtained by bronchoalveolar lavage (BAL) from a patient with gold lung. A 57-year-old man was admitted with progressive shortness of breath following a skin eruption. He had been receiving weekly sodium gold thiomalate (Shiosol) for rheumatoid arthritis, with a cumulative dose of 485 mg. Chest roentgenogram showed diffuse interstitial infiltrates. LST for the response to gold, using peripheral lymphocytes, was positive. T cell lymphocytosis was observed in BAL, and transbronchial lung biopsy showed lymphocytic alveolitis and granulation tissue in alveolar ducts. From these findings, we diagnosed gold lung. Prednisolone (PSL) was started with an initial dose of 30 mg/day and resulted in a rapid improvement. As the dose of PSL was tapered, the patient's condition deteriorated and he was treated with a maintenance dose of 10 mg PSL. The second BAL revealed persistent lymphocytosis, and LST using bronchoalveolar lymphocytes for response to gold was positive. LST using peripheral lymphocytes was also positive, but was weaker than that using bronchoalveolar lymphocytes. This is the first report in Japan of a positive LST for response to gold, using bronchoalveolar lymphocytes from a patient with gold lung. This case suggests that the presence of activated lymphocytes against gold in the lung is cumulative, and that cell-mediated hypersensitivity is related to gold lung.     

Amyopathic dermatomyositis with interstitial pneumonia: effective treatment with cyclophosphamide pulse therapy]

A 42-year-old man was admitted to our hospital because of dyspnea on exertion, skin eruptions on the face and extremities, and interstitial shadows mainly in the lower fields of both lungs. Characteristic skin lesions and skin biopsy findings without muscle symptoms or elevated CPK resulted in a diagnosis of amyopathic dermatomyositis (ADM). Thoracoscopic lung biopsy specimens disclosed BOOP-type interstitial pneumonia. Oral prednisolone (PSL) was initiated at 60 mg/day and gradually tapered. However, because his respiratory symptoms and laboratory findings deteriorated, the patient underwent 5 courses of cyclophosphamide (CPA) pulse therapy. Following improvement of his subjective symptoms, arterial blood gas data, and respiratory functions, the patient was discharged and placed on oral PSL and CPA. CPA was discontinued 18 months later. The patient has continued to receive PSL (5 mg/day) and has been in good condition for 3 years. Though the prognosis for interstitial pneumonia associated with ADM is reported to be poor, our patient represented a rare case of BOOP-type interstitial pneumonia brought into remission by CPA pulse therapy.     

Pharmacokinetics of prednisolone (PSL) during PSL treatment. II. PSL pharmacokinetics during intermittent treatment with PSL administration 4 consecutive days a week

Pharmacokinetics of prednisolone (PSL) was investigated in 10 patients treated with long-term intermittent regimen of PSL administration, 4 consecutive days administration a week. In 8 patients (group I; 3 of nephrotic syndrome, 2 of SLE, and each of Crohn's disease, aortitis syndrome, and hemolytic anemia), PSL was initially administered daily until the therapeutic effects were achieved (daily period), and this was followed by consecutive 4 days administration (on-day) and consecutive 3 days discontinuation (off-day) of PSL every week (intermittent period), keeping the weekly dose of PSL in the preceding daily regimen. In 2 patients (group II) with multiple myeloma and idiopathic thromocytopenic purpura, respectively, PSL was started with the intermittent regimen of PSL without preceding daily period. In group I, pharmacokinetic studies by respective oral and i.v. administrations of 40mg PSL and of 25.6mg PSL hemisuccinate (equivalent to 20mg of PSL) were performed before treatment, in daily period and both on on-day and off-day within the same week during intermittent period. In one patient of group II, study only by intravenous PSL administration was performed before treatment and in intermittent period. In another patient of group II, studies by oral and intravenous PSL administration were performed only in an intermittent period. PSL was measured by radioimmunoassay. Paired t-test was used for the comparison. In each case of group I, there was no difference in Cmax, Tmax, or AUCp.o. after oral administration of PSL among 4 periods tested, before treatment, daily period, on-day and off-day during intermittent period. On the intravenous PSL administration, increase in AUCi.v., prolongation of half-life, and decreases in MCR and bioavailability on on-day of intermittent period were observed in comparison with those before treatment, respectively. Only bioavailability among these parameters on on-day was increased compared with that in daily period. On the other hand, on off-day of intermittent period, decrease in AUCi.v. and increase in MCR were observed compared with those on on-day within the same week. When each parameter on off-day was compared with that of daily period, decrease in AUCi.v. and increases in MCR and bioavailability on off-day were observed. Vd did not differ each other among these 4 periods. Remarkable finding was the fact that MCR fluctuated regularly in 4 periods of this therapy regimen, i.e., significant decrease in daily period compared with before treatment, no significant difference between on-day and daily period, and the increase on off-day compared with that on on-day or in daily period.(ABSTRACT TRUNCATED AT 400 WORDS)     

Acquired chronic pure red cell aplasia successfully treated with intravenous pulse methylprednisolone therapy.

A 65-year-old male patient developed acquired chronic pure red cell aplasia (PRCA) associated with hypergammaglobulinemia and positive Coombs' test during the treatment of eosinophilic pneumonia with prednisolone (PSL). His PRCA was treated with oral PSL at a dose of 60 mg/day for 3 weeks, but anemia further progressed. Immediately after high-dose intravenous pulse methylprednisolone therapy (1 g/day for 3 days) however, reticulocyte crisis occurred and his anemia rapidly improved. He has been in complete remission under a maintenance dose of PSL for more than 2 years. This patient indicates that high-dose intravenous methylprednisolone therapy is one of the useful treatments, not only for constitutional PRCA, but also for acquired chronic PRCA.     

A case of systemic lupus erythematosus (SLE) with a neurogenic bladder, successful treatment with intravenous cyclophosphamide pulse therapy]

A 46-year-old woman was diagnosed as having systemic lupus erythematosus (SLE) in 1990 and was treated with a daily maintenance dose of prednisolone (PSL). She suddenly developed urinary incontinence with a high grade fever and erythema of the arms and legs on May 10, 1998 and was admitted to our hospital. Laboratory findings on admission showed proteinuria, pancytopenia and hypocomplementemia. Anti-nuclear antibody, anti-DNA antibody and anti-Sm antibody were positive. Ultra-sonography after urination revealed dilatation of the bladder. Cystometrography showed an autonomous neurogenic bladder. The diagnosis of neurogenic bladder complicated by peripheral neurone disturbance associated with recurrence of SLE was made and intravenous methylprednisolone (m-PSL) pulse therapy (1000 mg/day) was initially administered for 3 days followed by 60 mg of daily per os PSL. Urinary incontinence did not improved. The same therapy was conducted 3 times with no response. Therefore, treatment was started with intravenous cyclophosphamide pulse therapy (500 mg/day) which resulted in marked improvement of urinary incontinence, hypocomplementemia, proteinuria and pancytopenia. This case developed a neurogenic bladder caused by lower neurone disturbance but did not show central nervous system lupus with upper neurone disturbance. Neurogenic bladder caused by lower neurone disturbance in SLE has rarely been reported. The vasculitis of SLE was probably responsible for this neuropathy and this case was successfully treated with intravenous cyclophosphamide pulse therapy.     

Evaluation of recurrence in 36 subacute thyroiditis patients managed with prednisolone

OBJECTIVE: The incidence of subacute thyroiditis (SAT) is low and there are a few reports of recurrence of subacute thyroiditis. Current treatment protocols for SAT are not uniform. Prednisolone (PSL) is chosen more often for treatment than nonsteroidal anti-inflammatory drugs. This study was undertaken to confirm the recurrence rate of SAT managed by PSL, and to compare the initial laboratory data between the recurrent and the non-recurrent groups. METHODS: After diagnosis, all patients were treated with PSL (starting at 30 mg or 25 mg per day, tapered by 5 mg per week) for 5 or 6 weeks. We evaluated data and symptoms at the first visit and during the therapy. PATIENTS: Thirty-six patients who received only PSL for SAT at our hospital between January 1997 and December 1998 were referred. These patients asked to visit every 2 weeks for the monitoring of symptoms and laboratory data. RESULTS: SAT symptoms recurred in eight patients (22%), most upon cessation of PSL. There was no difference in initial serum sialic acid, erythrocyte sedimentation rate, C-reactive protein, thyroglobulin, serum free thyroxine and free triiodothyronine before PSL treatment between the recurrent and non-recurrent patient populations. CONCLUSIONS: The recurrence rate of SAT with treated PSL is about 20%. There was no difference in the laboratory data before starting the therapy between recurrent and non-recurrent groups. Therefore, a modified protocol of PSL administration may be needed to decrease the early recurrent rate of SAT.     

Therapeutic efficacy of intravenous cyclophosphamide concomitant with moderate- to high-dose prednisolone in two patients with fasciitis panniculitis syndrome

Abstract

Fasciitis panniculitis syndrome (FPS) has been proposed as a new category of ‘fasciitis’ and includes the well-established eosinophilic fasciitis (EF). Unlike EF, FPS exhibits inconsistent eosinophilia and/or eosinophilic infiltration of the lesions. Principal histological FPS findings include dermal thickening, inflammation and thickening of the subcutaneous fat tissue, fibrous thickening of the fascia and inflammation of the adjacent muscle. FPS is commonly resistant to corticosteroids, and cimetidine is effective in approximately 80% of FPS patients. A new therapy for FPS is required for cases refractory to treatment or intolerant to cimetidine because of adverse drug reaction. In this report, two FPS patients were resistant to corticosteroids. Both received intravenous cyclophosphamide (IVCY) concomitant with moderate- to high-dose prednisolone (PSL), and this effectively treated the induration of the FPS lesions. Patient 1 was a 50-year-old woman who had been diagnosed with fasciitis following en bloc muscle biopsy of the thigh. She had been treated with high-dose PSL for 6 years, but the fasciitis was refractory. Induration of the neck, thorax and thighs resulted in impaired neck rotation, restrictive respiratory failure and impaired walking. A diagnosis of FPS was made by re-assessing the en bloc muscle biopsy. Although PSL (40 mg/day) for 18 days was ineffective, the addition of IVCY (400 mg) dramatically improved the disease manifestations. Patient 2 was a 68-year-old man who was diagnosed with fasciitis based on en bloc muscle biopsy of the left foot. He had been treated with PSL for 16 years, but the fasciitis was refractory. He exhibited lower limb induration and a refractory skin ulcer of the left foot. A diagnosis of FPS was made by re-assessing the en bloc muscle biopsy. Although PSL (40 mg/day) for 2 weeks was ineffective, the addition of IVCY (450 mg) improved both the lower limb induration and the skin ulcer. FPS may cause both entrapment vasculopathy of subcutis and perivasculitis of the subcutaneous fat tissue such that the skin ulcer might be closely related with the ischemic mechanism triggered by FPS. According to the clinical courses of our cases, IVCY combined with moderate- to high-dose PSL may be a new therapeutic choice for corticosteroid-resistant FPS patients.     

Autoimmune pancreatitis with retroperitoneal fibrosis which responded to steroid therapy but was complicated with refractory renal dysfunction

A 58-year-old male had been diagnosed as having autoimmune pancreatitis (AIP) from the results of serological examinations and image findings. He was treated with prednisolone (PSL) for 3.5 months. Fifteen months later, follow-up CT revealed the main pancreatic duct (MPD) dilatation in the pancreas body to tail and right hydronephrosis caused by complicated retroperitoneal mass. We diagnosed him as having recurrent AIP with retroperitoneal fibrosis, and restarted PSL treatment. After one month, Examinations indicated amelioration of the MPD dilatation and right hydronephrosis, but not the right renal failure. This case indicates the importance of maintenance of PSL treatment.