Wataru Ishii

Severe protein losing enteropathy with intractable diarrhea due to systemic AA amyloidosis, successfully treated with corticosteroid and octreotide.

This report concerns two patients with severe protein losing enteropathy and refractory diarrhea due to AA amyloidosis who were successfully treated with corticosteroid and octreotide. In these patients, biopsied tissues from the gastrointestinal (GI) tract showed extensive deposition of AA amyloid, which was caused by rheumatoid arthritis in one case and was of unidentified etiology in the other. Both patients manifested severe diarrhea unresponsive to conventional treatment with hypoproteinemia, and protein leakage from the small intestine to the ascending colon was confirmed by 99mTc-diethylene triamine pentaacetic acid human serum albumin (HSA-D) scintigraphy. Soon after starting a long-acting somatostatin analogue, octreotide, with co-administration of oral prednisolone, their general status improved in parallel with a rapid decrease in the volume of watery diarrhea and an increase in serum levels of albumin and IgG. Also on 99mTc-HSA-D scintigraphy protein leakage from the GI tract was apparently decreased in both patients. Combination therapy with a somatostatin analogue and corticosteroid may be effective for protein losing enteropathy with intractable diarrhea ascribable to GI amyloidosis. Because of the lack of specific therapies in this serious clinical situation, the described therapy should actively be considered as a therapeutic option not only in AA amyloidosis, but also in other types of systemic amyloidosis.

VAD with or without subsequent high-dose melphalan followed by autologous stem cell support in AL amyloidosis: Japanese experience and criteria for patient selection.

Patients with AL amyloidosis were treated with VAD (vincristine, doxorubicin and dexamethasone) with or without high-dose melphalan followed by auto-PBSCT according to eligibility criteria based on disease severity, and prospectively investigated the therapeutic benefits and complications. Thirty-one patients were enrolled in this study. VAD and subsequent high-dose melphalan with auto-PBSCT were performed only in patients who met all of the eligibility criteria. Among patients ineligible for this treatment, VAD alone was performed in those with satisfactory general status. Eleven patients met the eligibility criteria, and of these, 7 were treated with VAD and subsequent high-dose melphalan with auto-PBSCT. Seven patients received VAD alone, and the remaining 17 were treated with the supportive therapy. Among the 14 patients treated with chemotherapy, 9 (5 of the 7 treated with VAD and high-dose melphalan, and 4 of the 7 treated with VAD alone) showed complete hematological response with apparent improvement of amyloidosis-related clinical symptoms. Serious complications of chemotherapy were cytomegalovirus infection and pneumocystis carinii pneumonia seen in 1 and 2 patients, respectively. These chemotherapies may be effective for reduction of M-protein and are also useful in improving of amyloidosis-induced organ dysfunction. In patients who cannot tolerate high-dose melphalan, VAD alone is a potent therapeutic option, although there are possible harmful effects on the heart and peripheral nerve.

Rituximab therapy in chronic inflammatory demyelinating polyradiculoneuropathy with anti-SGPG IgM antibody.

We report a patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who showed high titers of anti-sulfated glucuronyl paragloboside (SGPG) IgM antibody without M-protein in serum. The patient was resistant to corticosteroids and immunosuppressants, but after administration of rituximab, clinical symptoms improved and the patient remained in a stable state for approximately 10 months. Rituximab may be a potent therapeutic option for refractory cases of CIDP irrespective of detectable M-protein in either serum or urine.

Comparison of the histological and immunohistochemical features of the thymus in young- and elderly-onset myasthenia gravis without thymoma

We performed histological and immunohistochemical analyses of the removed thymuses from 20 elderly (onset age > 60 years) and 23 young (onset age < 40 years) patients with myasthenia gravis (MG) who tested positive for serum anti-acetylcholine receptor (AChR) antibodies, but who did not have associated thymoma. In the elderly group, nine (45%) patients had accumulations of lymphocytes, indicating an atrophied thymus with loss of the basic structure. The elderly MG patients with atrophied thymic tissues had higher titres of anti-AChR antibody (59.6+/-81.0 nmol/L) than those with adipose infiltration of the thymus alone (20.1+/-20.9 nmol/L). In immunohistochemical studies using image analysis, both young patients and elderly patients with atrophied thymic tissues were found to have significantly higher levels of CD20 than age-matched controls (p < 0.005). Atrophied thymic tissues, often seen immunohistochemically in young MG patients, may also be found in elderly patients, particularly in those with high titres of the anti-AChR antibody, even though adipose infiltration is marked in these patients.

Coadministration of tacrolimus with corticosteroid accelerates recovery in refractory patients with polymyositis/ dermatomyositis: a retrospective study

BackgroundTo investigate whether or not coadministration of tacrolimus (TAC) with prednisolone (PSL) can produce a beneficial effect in the treatment of polymyositis/ dermatomyositis (PM/DM).MethodsWe reviewed medical records of 32 PM/DM patients who had been admitted to our hospital, and abstracted those who had received TAC in addition to oral PSL for treatment. The clinical usefulness of TAC in PM/DM was objectively evaluated focusing upon the manual muscle strength test (MMT) score, serum creatine kinase (CK) and tapering of PSL.ResultsNine patients with PM and 6 with DM were enrolled in this study. TAC was added because of difficulty in reduction of PSL in 12 patients and recurrence with corticosteroid-induced complications in the remaining 3. Both PM and DM patients showed significant increases in the MMT score and significant decreases in serum CK 1 to 3 months after starting TAC compared with before. Skin symptoms in a clinically amyopathic DM patient also improved 1 month after starting TAC. The daily dosage of PSL could be significantly reduced in both PM and DM after starting TAC compared with before. No serious adverse events ascribable to TAC occurred in any patients.ConclusionAdditional use of TAC with PSL may safely promote improvement of PM/DM and also accelerate tapering of the latter.

A Young Man with Anti-NMDAR Encephalitis following Guillain-Barré Syndrome.

A 19-year-old man developed rapidly progressive muscle weakness and dysesthesia in the extremities, and dyspnea after a flu-like episode. Nerve conduction studies showed reduced motor nerve conduction velocities with conduction block, and sensory nerve action potentials could not be evoked. The patient was diagnosed as having Guillain-Barré syndrome (GBS), and was treated with 2 cycles of intravenous immunoglobulin (IVIg) therapy and was assisted by mechanical ventilation. During the recovery course of the illness, he experienced several attacks of psychomotor agitation from the 37th hospital day, and generalized tonic convulsive seizures suddenly developed on the 42nd hospital day. Brain MRI showed high-intensity lesions in the bilateral thalamus and medial temporal lobes. The convulsions were controlled by continuous thiopental infusion (until the 50th hospital day) and mechanical ventilation (until the 84th hospital day). Intravenous methylprednisolone pulse therapy (1,000 mg/day) for 3 days followed by dexamethasone (16 mg/day) was added. After relief of convulsive seizures, prominent orolingual dyskinesia appeared, and on MRI marked atrophy of the bilateral medial temporal lobes was seen. Anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in serum and cerebrospinal fluid were positive on the 92nd hospital day. Anti-NMDAR encephalitis usually affects young females but a small number of male cases with this disease have been reported. Our male patient was unique in having GBS, a post-infectious autoimmune disease, as a preceding disease, suggesting that anti-NMDAR encephalitis itself is caused by a parainfectious autoimmune mechanism.

Tacrolimus in refractory patients with myasthenia gravis: Coadministration and tapering of oral prednisolone

We prospectively investigated therapeutic and adverse effects of tacrolimus in seven patients with myasthenia gravis (MG) who were resistant to conventional therapies or could not be treated with thymectomy because of complications. Within two months of initiation of tacrolimus all the patients subjectively showed improvement of clinical symptoms, while both the quantitative MG score for disease severity and MG-activities of daily living profile were significantly decreased (p<0.05) 3 and 6 months after commencement compared with before. Nine months after initiation and later, MG temporarily exacerbated in two patients with rapid tapering of oral prednisolone and one non-thymectomized one. This drug is useful in the treatment of refractory patients with MG irrespective of thymectomy, particularly in the early phase after commencement. When tacrolimus is additionally used for treatment of MG, preceding drugs, particularly corticosteroids such as oral prednisolone, should be carefully tapered if necessary in order to prevent clinical exacerbation.

Phenotypes of Peripheral Blood Lymphocytes and Cytokine Expression in Polymyositis and Dermatomyositis before Treatment and after Clinical Remission

Objective To investigate peripheral blood lymphocyte subpopulations, particularly helper T (Th) cells and cytokine expression before and after treatment in polymyositis (PM) and dermatomyositis (DM). Patients and Methods Ten patients with PM and 15 with DM were enrolled in this study. As a control we used 11 age-matched healthy subjects. We analyzed peripheral blood lymphocytes using flow cytometry. Serum cytokines were determined by enzyme-linked immunosorbent assay. Results Th2/Th1 and Th2/Th17 ratios were significantly higher in both PM and DM than in controls and this Th2-predominancy is marked in DM associated with interstitial pneumonia. IL-1β, IL-6 and TGF-β were significantly higher in both PM and DM and IL-4 showed a significant increase in DM when compared to controls. There was no significant correlation between either any lymphocyte subpopulations or serum cytokines and clinical severity markers such as the manual muscle strength test, serum creatine kinase, and the total CT score. Th2/Th17 in both PM and DM, as well as Th2/Th1 in the latter, significantly decreased after clinical remission compared with before treatment. Conclusions Th2-predominancy as shown by the increase in Th2/Th1 and Th2/Th17 ratios may suggest active disease in PM/DM but does not reflect clinical severity.

Pneumatosis cystoides intestinalis in neuropsychiatric systemic lupus erythematosus with diabetes mellitus: case report and literature review

We report a patient with neuropsychiatric systemic lupus erythematosus (NPSLE) complicated by diabetes mellitus (DM) who showed pneumatosis cystoides intestinalis (PCI) while being treated with prednisolone (PSL) and an alpha-glucosidase inhibitor (αGI). The PCI was ameliorated with the cessation of the αGI and tapering of PSL in addition to transient fasting. Multiple factors, including NPSLE, DM, and medications, may have been involved in the pathogenesis of PCI in this patient.

Mixed connective tissue disease with interstitial pneumonia in HTLV-1 carrier: case report and review of the literature

We report on a carrier of human T-lymphotropic virus type 1 (HTLV-1) who developed mixed connective tissue disease (MCTD). This patient suddenly manifested clinical symptoms and interstitial pneumonia ascribable to MCTD following long-term infection with HTLV-1. After initiation of oral prednisolone all manifestations quickly improved in parallel with a decrease in inflammatory reactions. In this patient HTLV-1 infection might have played an important role in the pathogenesis of MCTD. Since HTLV-1 can cause adult T-cell leukemia and HTLV-1-associated myelopathy, and also collagen diseases including MCTD, careful observation is necessary even in a carrier, particularly when autoantibodies are detectable in serum.