Kenichi Komatsu

Recurrent attacks of autoimmune pancreatitis result in pancreatic stone formation.

OBJECTIVES:Autoimmune pancreatitis has been characterized by irregular narrowing of the main pancreatic duct and sonolucent swelling of the parenchyma, both of which are due to lymphoplasmacytic inflammation at the active stage of the disease, and by the absence of pancreatic stone formation. The aim of the present study was to confirm or deny whether or not this disease is progressive with recurrent attacks, resulting in pancreatic stone formation like ordinary chronic pancreatitis.METHODS:Forty-two patients, 36 of whom were treated with prednisolone, were followed up for periods longer than 12 months (median follow-up period: 54.5 months, range: 13–111 months) by regular interview and examination of their medical records for laboratory tests and image tests.RESULTS:Eleven patients (26.2%) who were treated with prednisolone showed recurrent attacks during median follow-up periods of 22 months. Eight patients (19%) showed the formation of pancreatic stones during the follow-up periods. Because 6 of 11 patients (54.5%) who suffered relapse showed pancreatic stone formation, it is significantly associated with relapse in comparison with nonrelapse (p = 0.0019).CONCLUSIONS:Contrary to previous reports, we observed both relapse and pancreatic stone formation in some patients with autoimmune pancreatitis, which suggests that autoimmune pancreatitis has the potential to be a progressive disease with pancreatic stones.

Immunoglobulin G4-related lymphoplasmacytic sclerosing cholangitis that mimics infiltrating hilar cholangiocarcinoma : part of a spectrum of autoimmune pancreatitis?

BACKGROUND Autoimmune pancreatitis has been designated as sclerosing pancreatocholangitis, because this disease shows a high prevalence of bile-duct lesions. We present herein the clinical characteristics of unusual cases that show dominant bile-duct lesions and mimicking infiltrating hilar cholangiocarcinomas. METHODS Clinical and pathologic findings of 3 patients with immunoglobulin (Ig) G4 related sclerosing cholangitis who had no apparent pancreatic lesions comparable with autoimmune pancreatitis were analyzed. OBSERVATIONS All patients were middle-aged or elderly individuals with slightly elevated serum IgG4 concentrations and showed long-segment narrowing of the bile-duct system, mimicking infiltrating hilar cholangiocarcinoma without significant pancreatic change. The first patient was treated with a corticosteroid, resulting in amelioration of the narrowing of the bile duct. The second patient underwent surgery based on a diagnosis of cholangiocarcinoma. In the third patient, the bile-duct stricture reversed spontaneously 1 month after the drainage procedure. Pathologic findings of the bile ducts for all patients disclosed significant lymphoplasmacytic infiltration, including abundant IgG4-bearing plasma cells. CONCLUSIONS The use of IgG4 immunostaining in biopsy specimens of the bile duct may identify the presence of corticosteroid-responsive lymphoplasmacytic sclerosing cholangitis.

Autoimmune pancreatitis and complement activation system.

Objectives: Autoimmune pancreatitis is characterized by increased serum level of IgG4, but its pathogenesis has not been fully elucidated. Because this disease is occasionally associated with decreased levels of complements, we sought to clarify which complement activation system was operating in its active state. Methods: We measured serum levels of complements, mannose-binding lectin, and circulating immune complex in patients with autoimmune pancreatitis, patients with chronic pancreatitis, and healthy controls. Results: We found high serum circulating immune complex values, which decreased significantly after corticosteroid therapy. In patients with autoimmune pancreatitis, elevated levels of circulating immune complex, as determined by C1q assay, were significantly associated with increased serum levels of IgG1 and decreased levels of C4, as well as with a tendency toward decreased levels of C3. There were no significant differences in the serum levels of mannose-binding lectin or in the frequency of a mutant allele of mannose-binding lectin between patients with autoimmune pancreatitis and those with chronic calcifying pancreatitis. Furthermore, corticosteroid therapy had no effect on the level of mannose-binding lectin. Conclusions: Autoimmune pancreatitis exhibits a high serum circulating immune complex values in its active state, which links to a complement activation system with a classic pathway rather than the mannose-binding lectin pathway or alternative pathways.

High prevalence of hypothyroidism in patients with autoimmune pancreatitis.

Autoimmune pancreatitis is a unique form of chronic pancreatitis and has been correlated with various extrapancreatic lesions. To search for a correlation between autoimmune pancreatitis and thyroid lesions, we measured thyroid functions in 41 patients with autoimmune pancreatitis and in 41 patients with chronic calcifying pancreatitis and investigated the correlation between HLA antigens and hypothyroidism. We found a significant difference in the prevalence of antithyroglobulin antibody and hypothyroidism between patients with autoimmune pancreatitis and those with chronic pancreatitis (34.1 vs. 7.3%, P = 0.005, and 26.8 vs. 0%, P = 0.0005, respectively). Patients with hypothyroidism had a significantly higher frequency of antithyroglobulin antibody (63.6%) than those without hypothyroidism but showed no differences in other findings, including serum IgG4 concentration. We could find no significant association between any HLA antigens and the hypothyroid state of autoimmune pancreatitis. One quarter of the patients with autoimmune pancreatitis have hypothyroidism that may be independent of the active state of the pancreatic lesion or systemic fibrosing disorder, and thus patients suspected of having autoimmune pancreatitis should be evaluated for possible hypothyroidism.

Corticosteroid-responsive pancreatic cyst found in autoimmune pancreatitis

There have been only a few reports of autoimmune pancreatitis complicated with pancreatic cyst and such cysts are rare, probably due to the absence of severe tissue necrosis and/or lack of stasis of the pancreatic juice in this condition. However, during a follow-up of 48 patients with this disease, we found 3 patients with pancreatic cysts, and this enabled us to evaluate their clinicopathological findings. Between September 1994 and July 2003, we treated and followed 48 patients with autoimmune pancreatitis, and found 3 patients with pancreatic cyst formation that was responsive to corticosteroid therapy. All of the patients with cysts had high serum IgG4 concentrations. After corticosteroid therapy, rapid resolution of the pancreatic cysts was observed. Immunostaining with goat polyclonal antibody for each IgG subclass showed severe infiltration of IgG4-positive plasma cells in the cyst wall in one patient. The high serum IgG4 concentration and favorable response to corticosteroid therapy suggests that a highly active state of the inflammatory process is closely associated with cyst formation, and that a corticosteroid-responsive pancreatic cyst is a characteristic feature of autoimmune pancreatitis.

Sudden-onset C8 Radiculopathy due to a Plexiform Schwannoma of the Cervical Nerve Root: A Case Report

Plexiform schwannoma is a rare variant of schwannomas and usually presents with chronic symptoms. We herein report a case of cervical nerve plexiform schwannoma that presented with unusually sudden severe left radiculopathy of the eighth cervical nerve after physical exercise. Coronal short-tau inversion recovery (STIR) magnetic resonance imaging (MRI) revealed a multinodular tumor along the eighth cervical nerve. The tumor was partially resected. A pathological analysis revealed that the tumor was a schwannoma, and we diagnosed the case as a plexiform schwannoma. The unusual sudden-onset presentation in this case was considered to be caused by the unusual localization of the tumor involving the nerve root and mechanical stress due to physical exercise.

Transient Diffusion-weighted Imaging Hyperintensity of the Cerebellar Cortex in Paraneoplastic Cerebellar Degeneration

A-53-year-old woman presented with a 2-week history of dysarthria and gait instability. On admission (day 1), a neurological examination revealed gaze-evoked nystagmus, mild dysarthria and severe truncal ataxia. Slight diffusionweighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) hyperintensity in the right cerebellar cortex were suspected on MRI (Picture). The cerebrospinal fluid (CSF) cell count was 20/μL, the protein level was 47 mg/ dL, and the cytology was negative. Anti-Yo antibodypositive paraneoplastic cerebellar degeneration (PCD) with presumed ovarian cancer was diagnosed after a thorough systemic work-up. Cerebellar symptoms progressed despite steroid pulse therapy, and MRI signal change moved to the bilateral upper portions of the cerebellum on day 21. The apparent diffusion coefficient (ADC) of the lesion was decreased in this second MRI (Picture). Although CSF findings normalized by day 29, the cerebellar symptoms progressed until paraaortic lymphadenectomy and plasma ex-

Hypertrophic Pachymeningitis in Sjögren's Syndrome

Although central nervous system manifestations seem common in primary Sjögrens syndrome, hypertrophic pachymeningitis is rare. We herein describe a case of Sjögrens syndrome that was associated with hypertrophic pachymeningitis. Sjögrens syndrome should be considered as a cause of hypertrophic pachymeningitis.

Rapidly Progressive Systemic Lupus Erythematosus-related Meningitis with Asymmetric Magnetic Resonance Imaging Findings

A 42-year-old man with systemic lupus erythematosus (SLE) was admitted with right hemiataxia. In addition to acute infarction in the left corona radiata, subdural diffusionweighted imaging (DWI) hyperintensity and subtle enhancement in the left subarachnoid space were detected (Picture, upper panels; arrow and arrowheads, respectively). Eleven hours later, he rapidly fell into a confused state with a preceding headache and fever. Broad fluid-attenuated inversion recovery (FLAIR) hyperintensity in the left subarachnoid space newly appeared (Picture, middle panels, arrows), but hemorrhage was excluded by computed tomography. SLErelated meningitis was considered, and steroid pulse therapy was started. He recovered fully by the next morning. Follow-up magnetic resonance imaging (MRI) two days later showed marked improvement (Picture, lower panels). Cerebrospinal fluid culture revealed negative findings. MRI abnormalities in SLE-related meningitis are rarely reported, and diffuse or bilateral subarachnoid FLAIR hyperintensity was observed in all four cases (1). The differential diagnoses of subarachnoid FLAIR hyperintensity have been reviewed elsewhere (2). The asymmetric subarachnoid FLAIR hyperintensity with subdural DWI hyperintensity in our case sug-

Multiple Myeloma Presenting with Autoimmune Autonomic Ganglionopathy

Autoimmune autonomic ganglionopathy is an autonomic disorder that occurs as a symptom of paraneoplastic neurological syndrome. To date, there have been no reports on multiple myeloma with autoimmune autonomic ganglionopathy. A 37-year-old Japanese woman suffered from orthostatic hypotension was diagnosed with multiple myeloma (IgG kappa type), and a serological examination revealed the presence of anti-ganglionic nicotinic acetylcholine receptor (anti-gAChR) antibodies. She was treated for multiple myeloma, as a result, the autonomic disturbance improved and her anti-gAChR antibody titer decreased to undetectable levels, despite the fact that she only achieved a partial remission of multiple myeloma. Treatment for multiple myeloma may improve autoimmune autonomic ganglionopathy.