Pyoderma gangrenosum in an ulcerative colitis patient during treatment with vedolizumab responded favorably to adsorptive granulocyte and monocyte apheresis

Pyoderma gangrenosum (PG) is an extra-intestinal skin lesion in inflammatory bowel disease (IBD) as is erythema nodosum. Vedolizumab (VED) is a monoclonal antibody that targets α4β7 integrin and has an intestinal selective mechanism. Despite good therapeutic effects on colitis, the effect on extra-intestinal manifestations (EIMs) remains unclear. Here we report a case of ulcerative colitis complicated by PG during treatment with VED, which was successfully treated with prednisolone in combination with adsorptive granulocyte and monocyte apheresis (GMA). The patient was a 50-year-old woman with a past medical history of extensive ulcerative colitis managed by golimumab (GLM). She developed flare symptoms due to loss of response to GLM, and treatment was switched to VED. Her gastrointestinal symptoms were improved with VED treatment with less frequent bowel movements. However, infiltrative erythema with pain appeared on the right lower leg and right knee, and expanded and gradually ulcerated. Her skin lesions were treated with corticosteroid, but showed poor improvement. Therefore, granulocyte and monocyte apheresis (GMA) treatment was administered in combination with prednisolone. After 3 months, the ulcer gradually improved, and at the time of this writing, the eruptions were nearly replaced by epithelial tissue. This case study showed that patients with UC and EIMS may respond well to combination therapy of VED and GMA. GMA has a very favorable safety profile. On the other hand, the causal connection between VED and PG is still unclear. We believe that a combination therapy involving VED and GMA in IBD patients with EIMs warrants consideration.     

Recurrence of hepatocellular carcinoma 102 months after successful eradication and removal of membranous obstruction of the inferior vena cava

We report a 54-year-old Japanese woman who developed liver tumors 102 months after hepatic resection for hepatocellular carcinoma (HCC) and percutaneous transluminal angioplasty (PTA) for membranous obstruction of the inferior vena cava (MOVC), which is one form of Budd-Chiari syndrome. In the present admission workup showed no evidence of co-infection with hepatitis B and C viruses. Dynamic computed tomography (CT) and magnetic resonance imaging showed an enhanced lesion, 1.5cm in diameter, in segment 3 of the liver, and no obstruction of the inferior vena cava after PTA. CT during both arterial portography and hepatic arteriography revealed another lesion, showing different hemodynamics, in segment 2. The patient therefore underwent hepatic resection, and the tumors were diagnosed histologically as HCC. The two tumors differed in their morphological features, one containing abundant fibrous stroma, whereas the other did not. The nontumorous liver tissue showed central zonal fibrosis, i.e., reversed lobulation, and partial expansion of nodule-like formations, indicating lack of progression since the situation seen at the initial hepatectomy. The presence of nontumorous liver tissue showing the above features suggests that, even after successful treatment for relief of congestion, patients who have had MOVC should be followed closely for as long as possible because of the risk of HCC recurrence. This is the first reported case of HCC recurrence after successful treatment of MOVC.     

A case of small cell lung carcinoma complicated by Lambert-Eaton myasthenic syndrome]

A 54-year old man was admitted with general fatigue, muscle weakness and dyspnea on effort. Medical examinations led to a diagnosis of small cell lung carcinoma (SCLC) with Lambert-Eaton myasthenic syndrome (LEMS). Marked improvement of SCLC and symptoms of LEMS were recognized twice during chemoradiotherapy. On his third admission, he showed muscle weakness, dysaethesia, and neurodysfunction of the bladder and rectum. We initially considered these symptoms to be due to spinal metastasis because MRI findings showed multiple spinal metastases. However, electoromyogram and nerve conduction study demonstrated that his muscle weakness resulted from LEMS though dysethesia and neurodysfunction of bladder and rectum were caused by spinal metastasis. We believe that it is important to perform electomyogram and nerve conduction studies, not only radiographic findings, to detect the "hidden" symptoms of LEMS.     

Systemic capillary leak syndrome

A 40-year-old woman was referred to our hospital with severe hypovolemic shock and anasarca. The laboratory findings showed marked hemoconcentration and a decrease in total serum protein with the presence of monoclonal IgG-lambda. She had had a similar episode of generalized edema 2 years previously. We diagnosed the patient as having typical systemic capillary leak syndrome (SCLS) and she improved gradually after infusion of albumin-containing fluid. SCLS is a very rare condition caused by unexplained episodic capillary hyperpermeability. Its treatment has remained largely supportive and the prognosis is generally poor. Awareness of SCLS is necessary for improvement of the outcome.     

Influenza A H1N1 pdm09‐associated myocarditis during zanamivir therapy

A 9‐year‐old girl developed influenza A H1N1 pdm09‐associated myocarditis and pericarditis 2 days after starting zanamivir therapy. The virus was detected in the respiratory tract but not in the serum or pericardial effusion. The virus sampled from the respiratory tract had normal susceptibility to neuraminidase inhibitors. Although no differences in interferon‐γ, interleukin (IL)‐1β, and tumor necrosis factor‐α were observed between the plasma and pericardial effusion, some inflammatory cytokines or chemokines (IL‐6 and IL‐8) and vascular endothelial growth factor were remarkably elevated in the pericardial effusion compared with the plasma. This suggested that the influenza virus, after infecting the respiratory tract, affected the myocardium, causing myocarditis to gradually develop, which might have been followed by an autoreactive pericarditis causing increased pericardial effusion. Therefore, influenza‐associated myocarditis should be considered when influenza patients have respiratory and cardiac involvement, even during treatment with a neuraminidase inhibitor.     

Triple valve replacement with bileaflet mechanical valves: is the mechanical valve the proper choice for the tricuspid position?

A more durable mechanical valve may be a better choice for the tricuspid position than a bioprosthesis when the patient already has mechanical prosthesis in the left side of the heart. Eleven cases of triple valve replacement (total follow-up period, 49.5 patient years), all with mechanical valves, are reviewed to assess optimal valve selection. Nine patients had undergone a total of 12 previous cardiac surgeries. Three patients died in hospital (27.3%), but there were no late deaths among the survivors. Two cases of valve thrombosis in the tricuspid position occurred (linearized incidence: 4.04%/patient years) and 1 of these required reoperation. Because of this high incidence of valve thrombosis, the bileaflet mechanical valve is not considered to be the best choice. Even if mechanical valves are implanted in the left side of the heart, a bioprosthesis may be a better choice at the tricuspid position.     

A Gain‐of‐Function Mutation in NALCN in a Child with Intellectual Disability,Ataxia, and Arthrogryposis

NALCN and its homologues code for the ion channel responsible for half of background Na⁺‐leak conductance in vertebrate and invertebrate neurons. Recessive mutations in human NALCN cause intellectual disability (ID) with hypotonia. Here, we report a de novo heterozygous mutation in NALCN affecting a conserved residue (p.R1181Q) in a girl with ID, episodic and persistent ataxia, and arthrogryposis. Interestingly, her episodes of ataxia were abolished by the administration of acetazolamide, similar to the response observed in episodic ataxia associated with other ion channels. Introducing the analogous mutation in the Caenorhabditis elegans homologue nca‐1 induced a coiling locomotion phenotype, identical to that obtained with previously characterized C. elegans gain‐of‐function nca alleles, suggesting that p.R1181Q confers the same property to NALCN. This observation thus suggests that dominant mutations in NALCN can cause a neurodevelopmental phenotype that overlaps with, while being mostly distinct from that associated with recessive mutations in the same gene.