Ko-ichi Tazawa

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.

Histopathological regression of systemic AA amyloidosis after surgical treatment of a localized Castleman's disease

Previously, we reported a case of localized plasma cell type Castlemans disease with severe hepatomegaly and reactive systemic AA amyloidosis. The amyloid deposits were demonstrated in both the hepatic tissue and in the gastric mucosa. Surgical resection of an isolated extra-hepatic tumor was performed. The laboratory findings, including SAA and IL-6, remained within normal limits and the patients hepatomegaly subsequently showed regression. Nine years after the operation, no amyloid deposition was seen in the gastric mucosa and the patients liver was of normal size. Our findings with long-term follow up in this case indicated that the cessation of SAA production was the probable cause of histopathological regression of AA amyloid deposits in this patient.

A 73-year-old patient with adult-onset type II citrullinemia successfully treated by sodium pyruvate and arginine.

Citrin deficiency, caused by a mutation of the SLC25A13 gene, s an autosomal recessive disorder that leads to neonatal intraheptic cholestasis caused by citrin deficiency (NICCD) and adult-onset ype II citrullinemia (CTLN2) [1]. The function of citrin is imporant in translocating cytosolic NADH reducing equivalents into he mitochondria as part of the malate-aspartate shuttle [2]. In ddition, citrin plays an important role in supplying aspartate o argininosuccinate synthetase (ASS) in the cytosol to generte argininosuccinate in the urea cycle [2]. Thus, a deficiency f citrin results in dysfunction of the urea cycle and hyperamonemia [1]. Patients with CTLN2 present with sudden onset of arious encephalopathic manifestations due to hyperammonemia 2]. One of the distinct features of citrin deficiency is that the ajority of patients have a peculiar fondness for proteinand at-rich foods, such as beans and peanuts, and an aversion to arbohydrate-rich foods, such as rice, sweets, and alcohol [2]. It is ssumed that their unique food preference may be directly related

An autopsy case with adult onset type II citrullinemia showing myelopathy

Hepatic myelopathy is a rare neurological complication in patients with chronic liver failure and most patients who suffered from this disorder were demonstrated to have portal-systemic shunt. A 31-year-old man who was diagnosed as having adult-onset type II citrullinemia (CTLN2) and had a six-year history of recurrent hepatic encephalopathy showed progressive spastic paraparesis with no involvement of sensation and sphincter function. Examinations of cerebrospinal fluid and spinal MRI were normal. He suddenly died of acute exacerbation of hepatic encephalopathy with severe brain edema. The pathology of the spinal cord disclosed a localized degeneration of both lateral columns, the lesion being more remarkable in the lower segments of the cord. These clinical and pathological findings of hepatic myelopathy have not been noted in the many patients with CTLN2 previously reported, and our patient is unique in developing hepatic myelopathy without porto-caval shunting. Thus, repeated attacks of encephalopathy with hyperammonemia might secondarily have induced the myelopathy in this patient.

coadministration of cyclosporin A with prednisolone in Acute Interstitial pneumonia complicating polymyositis/Dermatomyositis

Objective To investigate clinical effectiveness of prednisolone (PSL) and cyclosporin A (CyA), particularly continuous intravenous administration of the latter, in patients with interstitial pneumonia (IP) associated with polymyositis/dermatomyositis (PM/DM). Methods We reviewed the clinical findings and therapeutic outcomes of patients with PM/DM who had received PSL and CyA (PSL + CyA, n = 21 for DM and 2 for PM) or the former alone (n = 12 for DM and 7 for PM). All patients receiving PSL + CyA had active IP. Results Fifteen of the 21 DM patients receiving PSL + CyA showed favorable therapeutic outcomes of IP (recovery group), while the remaining 6 died of respiratory failure (death group). Before treatment PaO2 in room air and %VC were significantly lower, and the total CT score was significantly higher in the death group than in the recovery one. Continuous intravenous administration of CyA was performed in 6 patients for severe IP requiring oxygen therapy, and of these 2 showed complete recovery from it. Conclusions Coadministration of PSL and CyA, particularly continuous intravenous infusion of the latter, from the early phase of illness may be a potent therapeutic option for PM/DM patients with decreases in PaO2 and %VC and/or a high total CT score suggestive of a poor prognosis.

Severe cranial nerve involvement in a patient with monoclonal anti-MAG/SGPG IgM antibody and localized hard palate amyloidosis

We report a patient with severe cranial polyneuropathy as well as sensory limb neuropathy. Biclonal serum IgM-kappa/IgM-lambda gammopathy was found and serum anti-myelin-associated glycoprotein (MAG)/sulfoglucuronyl paragloboside (SGPG) IgM antibody was also detected. Immunofluorescence analysis of a sural nerve biopsy specimen revealed binding of IgM and lambda-light chain on myelin sheaths. No amyloid deposition was detected in biopsied tissues except for the hard palate, suggesting that the amyloidosis was of the localized type and had no relation to the pathogenesis of cranial neuropathy. Our observations indicate that the anti-MAG/SGPG IgM antibody may be responsible for this patients cranial polyneuropathy, which is a rare manifestation in anti-MAG/SGPG-associated neuropathy.

Patient with adult‐onset type II citrullinemia beginning 2 years after operation for duodenal malignant somatostatinoma: Indication for liver transplantation

We report a 51‐year‐old female patient with adult‐onset type II citrullinemia (CTLN2) who had a history of pancreatoduodenectomy for duodenal somatostatinoma with metastases to regional lymph nodes at age 49 years, paying special attention to indications for liver transplantation. At age 50 years, she developed hepatic encephalopathy with elevation of plasma ammonia and citrulline levels. A diagnosis of CTLN2 was made by DNA analysis of the SLC25A13 gene and treatment with conservative therapies was begun, including a low‐carbohydrate diet and supplementation with arginine and sodium pyruvate. However, despite these treatments, frequent attacks of encephalopathy occurred with markedly elevated plasma ammonia levels. While we were apprehensive regarding the risk of recurrence of somatostatinoma due to immunosuppressive therapy after liver transplantation, the patient was in a critical condition with CTLN2 and it was decided to perform living‐donor liver transplantation using a graft obtained from her son. Her postoperative clinical course was uneventful and she has had an active life without recurrence of somatostatinoma for 2 years. This is the first case of CTLN2 with somatostatinoma. As the condition of CTLN2 patients with rapidly progressive courses is often intractable by conservative therapies alone, liver transplantation should be considered even after surgery for malignant tumors in cases with neither metastasis nor recurrence.

Polyarteritis nodosa with central nervous system involvement mimicking relapsing–remitting multiple sclerosis

Abstract We report a patient with polyarteritis nodosa (PN) who showed frequent episodes of acute-onset central nervous system (CNS) involvement mimicking relapsing–remitting multiple sclerosis (MS) for 22 years. Long-term use of oral prednisolone successfully avoided recurrence of neurological symptoms. PN can sometimes affect the CNS, and is an important item in the differential diagnosis of neurological manifestations with lesion dissemination in time and space, as seen in MS.

First two cases of adult-onset type II citrullinemia successfully treated by deceased-donor liver transplantation in Japan.

We report the first two cases of adult‐onset type II citrullinemia (CTLN2) successfully treated by liver transplantation from deceased donors in Japan. One patient was a 34‐year‐old female, who had suffered from depression since the age of 28 years and developed consciousness disturbance at 34 years old. The other patient was a 41‐year‐old man who began to experience consciousness disturbance with abnormal behavior at 37 years old. Both patients were first treated with non‐surgical therapies, including low‐carbohydrate diet, arginine granules and sodium pyruvate. However, their therapeutic efficacy was limited and attacks of encephalopathy occurred frequently with elevation of plasma ammonia despite treatment. While both patients and their families desired liver transplantation, no candidate donors for live‐donor liver transplantation were available. Fortunately, within a relatively short period after enrollment for liver transplant from deceased donors in Japan (13 and 43 days, respectively), they underwent cadaveric liver transplantation. The clinical courses after the operation were uneventful in both cases and no attacks of hepatic encephalopathy have occurred. Although there have been no reports of good therapies for CTLN2 patients with resistance to non‐surgical therapies and no live‐donor candidates, our observations indicate that cadaveric liver transplantation can be a promising therapeutic option for CTLN2 patients.

Surgical removal of amyloid-laden lymph nodes: a possible therapeutic approach in a primary systemic AL amyloidosis patient with focal lymphadenopathy

We report a patient with primary systemic AL amyloidosis who suffered from remarkable bilateral cervical lymphadenopathy. Intensive chemotherapies, including two cycles of high-dose melphalan with autologous peripheral blood stem cell transplantation, were insufficiently effective for both the lymphadenopathy and amyloidogenic IgGλ-type M-protein in serum, but the patient showed complete haematological remission after extensive surgical removal of enlarged lymph nodes that had massive depositions of λ-type immunoglobulin light chain-derived amyloid. Lymphadenectomy may be a possible therapeutic approach with regard to both cosmetic and haematological aspects in primary systemic AL amyloidosis patients with focal lymphadenopathy.