Graves' disease presenting with severe cholestasis

BACKGROUND: Hyperthyroidism has been associated with liver function abnormalities; however, cholestasis as the presenting feature of adolescent Graves' disease has not been previously reported. PATIENT SUMMARY: The patient was a 17-year-old girl who presented with severe cholestasis and was found to have Graves' disease. She also had a positive hepatitis A immunoglobulin M antibody but her clinical course, the liver histopathology, and her mildly elevated transaminases indicated that the acute hepatitis A infection was not dominant at the time of presentation with severe cholestasis. Other causes of cholestasis, including congestive heart failure, autoimmune hepatitis, and viral infection, were excluded. Treatment with methimazole resolved the hyperthyroidism, and the cholestasis improved, as well. CONCLUSION: Severe cholestasis is a rare presenting feature of Graves' disease. With careful monitoring, methimazole can be used to treat the hyperthyroidism in the setting of cholestasis.     

Small Nerve Fiber Damage and Langerhans Cells in Type 1 and Type 2 Diabetes and LADA Measured by Corneal Confocal Microscopy

PurposeIncreased corneal and epidermal Langerhans cells (LCs) have been reported in patients with diabetic neuropathy. The aim of this study was to quantify the density of LCs in relation to corneal nerve morphology and the presence of diabetic neuropathy and to determine if this differed in patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and latent autoimmune diabetes of adults (LADA).MethodsPatients with T1DM (n = 25), T2DM (n = 36), or LADA (n = 23) and control subjects (n = 23) underwent detailed assessment of peripheral neuropathy and corneal confocal microscopy. Corneal nerve fiber density (CNFD), branch density (CNBD), length (CNFL) and total, immature and mature LC densities were quantified.ResultsLower CNFD (P < 0.001), CNBD (P < 0.0001), and CNFL (P < 0.0001) and higher LC density (P = 0.03) were detected in patients with T1DM, T2DM, and LADA compared to controls. CNBD was inversely correlated with mature (r = –0.5; P = 0.008), immature (r = –0.4; P = 0.02) and total (r = –0.5; P = 0.01) LC density, and CNFL was inversely correlated with immature LC density (r = –0.4; P = 0.03) in patients with T1DM but not in patients with T2DM and LADA.ConclusionsThis study shows significant corneal nerve loss and an increase in LC density in patients with T1DM, T2DM, and LADA. Furthermore, increased LC density correlated with corneal nerve loss in patients with T1DM.     

Small Fiber Neuropathy: Is Skin Biopsy the Holy Grail?

Small fiber neuropathy (SFN) is characterized by negative sensory symptoms (thermal and pinprick hypoesthesia) reflecting peripheral deafferentation and positive sensory symptoms and signs (burning pain, allodynia, hyperalgesia), which often dominate the clinical picture. In patients with pure SFN, clinical and neurophysiologic investigation do not show involvement of large myelinated nerve fiber making the diagnosis of SFN challenging in clinical practice. Over the last 15 years, skin biopsy has emerged as a novel tool that readily permits morphometric and qualitative evaluation of somatic and autonomic small nerve fibers. This technique has overcome the limitations of routine neurophysiologic tests to detect the damage of small nerve fibers. The recent availability of normative reference values allowed clinicians to reliably define the diagnosis of SFN in individual patients. This paper reviews usefulness and limitations of skin biopsy and the relationship between degeneration and regeneration of small nerve fibers in patients with diabetes and metabolic syndrome.     

Vitamin D3 modulates T lymphocyte responses in hepatitis C virus-infected liver transplant recipients

Background

Aim of the present study was to investigate whether 1,25(OH)(2)D(3) (Vitamin D3) modulates T lymphocyte functions in patients transplanted for hepatitis C virus-related cirrhosis.

Methods

Sixteen patients and ten healthy subjects were investigated. T lymphocytes were activated in vitro in the presence or absence of Vitamin D3 and then the proliferative response and IFN-γ and TNF-α production were assessed.

Results

Vitamin D3 potently reduced T-lymphocyte proliferation in a dose-related fashion. Similarly, FACS analysis and ELISA testing demonstrated that Vitamin D3 significantly decreased the response frequency and the response intensity of IFN-γ and TNF-α production in the whole CD3-positive T lymphocyte population as well as in “naive” CD4+ CD45RA+ and “memory” CD4+ CD45RO+ T lymphocyte subsets. The inhibitory effect of Vitamin D3 on T-cell proliferation and cytokine production was not different between patients and controls. No toxic effects were exerted by Vitamin D3 even at the higher concentration used (10 nM). Finally, no statistically significant correlation was found between 25(OH)D serum levels and the proliferative response or cytokine production of T lymphocytes from transplanted patients.

Conclusions

This study demonstrates that in patients transplanted for hepatitis C virus-related cirrhosis Vitamin D3 modulates T lymphocyte activation, and provides a rationale for the evaluation of this compound as an immunosuppressive agent in liver-transplanted patients.