Fatal progressive hepatic necrosis associated with lamotrigine treatment: a case report and literature review

We present a case of fatal, progressive hepatotoxicity in a patient treated with lamotrigine. After presenting with a rash and fever, she developed elevated liver function tests and clinical sequelae of hepatic failure. The subacute course of her progressive liver damage is documented in serial liver biopsies. While her initial biopsy showed approximately 50% hepatocyte necrosis, her post mortem examination performed three weeks later displayed massive hepatic necrosis with extensive bile duct proliferation. Although she was taking other antipsychotics at the time, her clinical course best parallels other reports of lamotrigine-associated hepatotoxicity. Here we discuss not only the clinicopathologic findings of this case but also review the pertinent literature.     

RAPID DEVELOPMENT OF CEREBRAL ATROPHY IN SYSTEMIC LUPUS ERYTHEMATOSUS

A 21-year-old female is described who developed severe cerebrallupus 9 months after the onset of her disease. A dramatic changein her CT brain scan from normal to gross cerebral atrophy wasobserved in the month following onset of her cerebral disease. This patient developed hepatitis during the course of her hospitalization.This is an unusual manifestation of systemic lupus. The patient'sserum also contained anti-Sm antibodies. This is a relativelyinfrequent finding in the serum of lupus patients outside theUnited States. KEY WORDS: Systemic lupus erythematosus, Cerebral disease, Sm antibodies     

Patients with severe liver cirrhosis followed up by L-[1-13C] phenylalanine breath test

Compared to healthy subjects, patients with severe liver cirrhosis (LC) are reported to show lower values in the L-[1-¹³C] phenylalanine breath test (PBT). We performed this test several times during the clinical course in two patients with severe liver cirrhosis (LC). Patient 1 was a 67-year-old woman with non-B, non-C LC and hepatocellular carcinoma (HCC) in the lateral hepatic segment. Because the patient wanted to receive nonsurgical treatment for HCC, intraarterial administration of zinostatin stimalamer was performed. The patient was hospitalized four times before her death from liver failure on December 20, 2000. During her clinical course, PBT was performed four times. Values for both the rate of hepatic phenylalanine oxidation (%¹³C dose h^–1) and %¹³C cumulative excretion gradually decreased during her clinical course. Patient 2 was a 57-year-old man with hepatitis C virus (HCV)-positive LC. He was hospitalized seven times between December 1998 and his death on May 24, 2001. During his clinical course, PBT was performed four times. Values for both %¹³C dose h^–1 and %¹³C cumulative excretion decreased during his clinical course. We confirmed that PBT was useful for following the course of LC.     

The role of apheresis in the support of life-threatening ITP relapse

A 14-year-old girl with chronic idiopathic thrombocytopenic purpura (ITP) presented in relapse with a platelet count of 1,000/microL and a high-level serum antiplatelet IgG antibody. She previously had been unresponsive to courses of therapy with steroids, vincristine, and splenectomy. When treatment with danazol and purified immunoglobulins was unsuccessful in controlling her rapidly progressive course, an 8-day plasma exchange procedure was initiated in combination with platelet transfusion therapy and immunosuppression with cyclophosphamide and vincristine. Within 2 days, her clinical state improved markedly, correlating with a drop in her serum antiplatelet antibody level. She continued to improve and was discharged on a regimen of cyclophosphamide and danazol. Her antiplatelet antibody level had fallen to within the normal range, despite a typical platelet count of 5,000/microL during the 8-day period. Two weeks later her platelet count rose to 65,000/microL. This case suggests that a course of therapeutic plasma exchange may have a temporizing role in the acute management of life-threatening chronic ITP relapse, generating time for the more definitive therapy of immunosuppression to take effect.     

Gastrointestinal mucormycosis complicated by arterio-enteric fistula in a patient with non-Hodgkin's lymphoma

Gastrointestinal mucormycosis is a rare, often fatal, systemic infection found predominantly in immunocompromised patients. We report a case of gastrointestinal mucormycosis in a 53-year-old female with non-Hodgkin's lymphoma. Following her first course of chemotherapy, bowel obstruction developed as a result of mucormycosis. Despite treatment with antifungal therapy, she required a laparotomy owing to severe haemorrhage caused by mucormycosal invasion of her iliac artery. With continued antifungal treatment and further chemotherapy, she ultimately underwent reversal of her Hartmann's procedure and remains disease-free.     

Extensive soft tissue calcification (calcinosis universalis) in systemic lupus erythematosus.

A 21-year-old woman with long-standing systemic lupus erythematosus developed extensive calcification of the soft tissues of the thoracic and abdominal walls and extremities early in her illness, and these calcifications gradually disappeared over the course of her disease. The extent of this calcinosis and apparent spontaneous regression are unusual events in systemic lupus erythematosus.     

Exacerbation of pulmonary lymphangioleiomyomatosis by exogenous estrogens

A 48-year-old woman with profound, rapidly progressive dyspnea requested a second opinion regarding the diagnosis and management of an undiagnosed interstitial process. One year prior to this evaluation, she had been placed on therapy with exogenous estrogens for the treatment of osteoporosis. During this therapy, she had a marked deterioration of her pulmonary status. Review of her open lung biopsy, which was obtained five years previously, revealed lymphangioleiomyomatosis. Discontinuation of estrogen therapy and treatment with tamoxifen were successful in stopping the progressive course. This patient's clinical course suggested an association between estrogen therapy and clinical deterioration during the menopause.     

FLAG chemotherapy followed by allogeneic stem cell transplant using nonmyeloablative conditioning induces regression of myelofibrosis with myeloid metaplasia

A 38-year-old woman with agnogenic myeloid metaplasia complicated by the poor prognostic factors of severe osteosclerosis, prominent hepatosplenomegaly, and profound anemia was treated with FLAG chemotherapy to decrease her organomegaly before undergoing a nonmyeloablative allogeneic stem cell transplant from a matched-sibling donor. The patient's pre- and post transplant course were complicated by an autoimmune disorder and her post transplant course was complicated by severe hepatic and gastrointestinal GVHD. A technetium-99m sulfur colloid scan 4 months post transplant and bone marrow studies 8 months post transplant demonstrated intramedullary hematopoiesis, complete resolution of marrow fibrosis, and partial resolution of osteosclerosis.     

A case of tsutsugamushi disease in the urban area of Komatsu City

Most of patients with tsutsugamushi disease are diagnosed by their clinical histories suggesting the opportunities of Rickettsia infection in a rural region. We reported a 76-year-old female patient, who was considered to be infected in her house in the urban area of Komatsu City. She has shown typical clinical manifestations of tsutsugamushi disease, and was remitted successfully by oral administration of minocycline. Although specific antibodies to Rickettsia tsutsugamushi could not be detected in her serum by the complement fixation (CF) method during her clinical course, their significant elevation was confirmed by the indirect immunofluorescence (IF) method.     

Pregnant woman with non‐comatose autoimmune acute liver failure in the second trimester rescued using medical therapy: A case report

We present the case of a 25‐year‐old woman at 16 weeks of gestation who presented with non‐comatose autoimmune acute liver failure and was at high risk of developing fulminant hepatitis. Predictive formulas indicated a high probability of developing fulminant hepatitis. Unenhanced computed tomography showed marked hepatic atrophy and broadly heterogeneous hypoattenuating areas. The course of her illness was subacute, and the etiology of liver injury was unclear. Considering all of the above, we predicted a poor prognosis. Plasma exchange (PE) and continuous hemodiafiltration (CHDF) therapy were initiated just after admission. A few days after admission, a high titer (×80) of antinuclear antibody was noted. Because autoimmune hepatitis (AIH) was considered a cause of liver failure, treatment with moderate prednisolone (30 mg/day) doses was administrated, with careful consideration of her pregnancy. Thereafter, her laboratory findings and clinical course gradually improved without the need for liver transplantation. A liver biopsy at 18 days after admission indicated a diagnosis of AIH. She continued the pregnancy and delivered a healthy baby without any complications. Eventually, prednisolone doses were decreased to 10 mg, after which her liver function worsened. The second liver biopsy also indicated a diagnosis of AIH. Accordingly, low‐dose prednisolone and azathioprine doses (50 mg/day) were administrated to recover her liver function, after which her liver function regained normalcy. This case illustrates that a pregnant woman with non‐comatose autoimmune acute liver failure in the first or second trimester of pregnancy and her fetus can be rescued by PE/CHDF therapy and safe moderate doses of prednisolone.     

Peripheral arterial coil embolization for hepatic arteriovenous malformation in Osler-Weber-Rendu disease; useful for controlling high output heart failure, but harmful to the liver

A 55-year-old Japanese housewife, who had Osler-Weber-Rendu disease, was admitted to our hospital because of frequent epistaxis and worsening exertional dyspnea. The computed tomography and hepatic arteriography revealed large hepatic arteriovenous malformation, which was considered to be the leading cause of her high output heart failure. Two series of hepatic arterial coil embolization procedures were performed to reduce hepatic shunt flow. They temporarily improved her cardiac condition, but gradually induced progressive hepatic failure due to intrahepatic cholangitis. Hepatic dysfunction restricted her quality of life and lead to a fatal clinical course one year after the second coil embolization.     

Hypothyroidism associated with mixed connective tissue disease and its response to steroid therapy.

The case is reported of a 49-year-old housewife who presented with arthralgia and severe Raynaud's phenomenon. A diagnosis of mixed connective tissue disease (MCTD) was made on the basis of the clinical picture and serological findings. During the course of her disease she developed hypothyroidism. She was started on prednisolone to control the symptoms of the MCTD, and after this her thyroid function returned to normal despite her never having had any thyroid replacement therapy. There is reported evidence that Hashimoto's thyroiditis responds to systemic steroid preparations, but we can find no report of hypothyroidism in MCTD having a similar response.     

Crohn's disease associated with autoimmune neutropenia

We report a 29-year-old woman with a 20-year history of Crohn's disease and neutropenia. Because of repeated complications of Crohn's disease, she has undergone three intestinal resections and also has had recurrent skin abscesses, sinusitis, and pneumonia. Persistent neutropenia has been noted throughout the course of her disease, and antineutrophil antibodies have been detected in her serum and that of her younger brother, who also has Crohn's disease and neutropenia. We discuss autoimmune neutropenia in the context of other autoimmune manifestations of Crohn's disease and speculate as to its possible contributory role in the pathogenesis of Crohn's disease.     

Anti-glutamic acid decarboxylase antibodies in a patient with systemic lupus erythematosus and fibromyalgia symptoms

We report the case of a 29-year old female nurse with a five-year history of systemic lupus erythematosus (SLE) involving multiple systems and on chronic prednisone therapy. This patient has a coexisting diagnosis of fibromyalgia fulfilling ACR criteria. A recent deterioration in her level of functioning in addition to a flare of her inflammatory disease led to further evaluation. During the course of investigation an anti-glutamic acid decarboxylase antibody was found to be present and significantly elevated. A therapeutic trial of baclofen did result in improvement of her subjective myalgias. We raise the possibility of an autoimmune contribution to myalgic symptoms in a portion of SLE patients.     

Intra-vascular ultrasound findings of diffuse coronary atherosclerotic change in systemic lupus erythematosus with secondary antiphospholipid syndrome.

Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are autoimmune inflammatory diseases associated with juvenile atherosclerosis and thrombosis, respectively. A 44-year-old woman who had SLE with secondary APS had been treated with corticosteroid therapy, however, her inflammatory marker had never been within a normal range in her clinical course, and finally acute myocardial infarction was developed. Intra-vascular ultrasound also revealed diffuse coronary atherosclerosis progression for her age, which might result from SLE and APS, including vascular inflammation.     

Gastrointestinal mucormycosis complicated by arterio‐enteric fistula in a patient with non‐Hodgkin's lymphoma

Gastrointestinal mucormycosis is a rare, often fatal, systemic infection found predominantly in immunocompromised patients. We report a case of gastrointestinal mucormycosis in a 53‐year‐old female with non‐Hodgkin's lymphoma. Following her first course of chemotherapy, bowel obstruction developed as a result of mucormycosis. Despite treatment with antifungal therapy, she required a laparotomy owing to severe haemorrhage caused by mucormycosal invasion of her iliac artery. With continued antifungal treatment and further chemotherapy, she ultimately underwent reversal of her Hartmann's procedure and remains disease‐free.     

A case of drug-induced ductopenia resulting in fatal biliary cirrhosis

ABSTRACT— A 50-year-old woman suffered from a diffuse skin rash, high fever and jaundice immediately after a second injection of glutathion and Stronger Neo-minophagen C which contains glycyrrhizin. Liver biopsy performed 11 months after the onset showed mild spotty hepatocyte necrosis, marked cholestasis in parenchyma, and some lymphocyte infiltration in the portal area. Interlobular bile ducts had undergone vacuolar degeneration or were absent in some portal tracts. In her hospital course, unremitting jaundice persisted and biliary cirrhosis developed with signs of portal hypertension; she died from liver failure 26 months after the onset. A liver specimen at her death revealed that most of the interlobular bile ducts had vanished. Based on the clinical course and pathology, drug-induced ductopenia, possibly due to an adverse reaction to glycyrrhizin, is the most likely diagnosis. While drug-related biliary cirrhosis is rarely fatal, this case presented an unusually rapid course of fatal biliary cirrhosis.     

Congenital hypoplastic anemia (Diamond-Blackfan syndrome) terminating in acute myelogenous leukemia.

A 31-yr-old female with congenital hypoplastic anemia (Diamond-Blackfan syndrome) whose long course terminated in acute myelogenous leukemia is described. In contrast to Fanconi anemia, malignant transformation rarely occurs in congenital hypoplastic anemia. This patient's diagnosis of congenital hypoplastic anemia is supported by her clinical course, absence of renal abnormalities, a negative family history for hematologic disorders, normal chromosome studies, failure of her skin fibroblasts to transform in culture with SV-40 virus, macrocytic erythrocyte indices, erythrocyte enzyme studies, and bone marrow findings. Only two other cases of malignancy have been reported in patients with congenital hypoplastic anemia. The development of malignancy in these patients suggests that malignant transformation may be a concern in the long-term progression of congenital hypoplastic anemia.     

A 2-year-old Japanese girl with TNF receptor–associated periodic syndrome: A case report of the youngest diagnosed proband in Japan

We report a 2-year-old girl with tumor necrosis factor receptor–associated periodic syndrome (TRAPS) who is the youngest proband diagnosed in Japan. Recurrent fever had started at her 6 months of age, and she had the familial history of recurrent fever, suggesting underlying genetic disorder, in her father and grandfather. Careful clinical observation of characteristics of fever with disease course and the familial history of recurrent fever may lead to diagnosis of TRAPS in early infancy.     

Adult hemolytic uremic syndrome associated with nonimmune deposit crescentic glomerulonephritis and alveolar hemorrhage

An 18-year-old girl presented with anuric rapidly progressive glomerulonephritis associated with hypoxemic respiratory failure due to diffuse lung hemorrhage. The course of the kidney disease terminated in end-stage renal failure. The patient had been on permanent hemodialysis since her first admission; episodes of lung hemorrhage recurred five times over a follow-up period of 8 months. Two months after her first admission, the patient manifested features suggestive of the hemolytic uremic syndrome, namely, microangiopathic hemolytic anemia, thrombocytopenia, and excessive hypertension complicated by hypertensive encephalopathy. Based on the sequence of events in the course of this patient's disease, the authors believe that the hematological abnormalities were superimposed on the glomerular disease rather than being a primary disorder. Possible mechanisms for the association of the two disorders are discussed.