Unmasking of autoimmune hepatitis in a patient with MS following interferon beta therapy

Abstract

Dystonia is frequent in early-onset parkinsonism (EOP) and sometimes its presenting sign. 1,2 Conversely, parkinsonian signs occur in dopa-responsive dystonia (DRD), especially in later stages, and may even be the only finding in relatives of patients with clinically typical DRD. 3 Both conditions may have a similar age at onset and respond well to treatment with levodopa, and patients may report sleep benefit and diurnal variation of symptoms in both conditions. Due to this phenotypic overlap, categorization of the early-onset dystonia-parkinsonism syndromes may pose a diagnostic challenge.Dominantly, inherited mutations in the GTP cyclohydrolase I (GCHI) gene can be found in over 80% of the clinical typical cases of DRD but only when conventional screening methods and expensive gene dosage analyses are combined. 4 The most common known cause of EOP is recessively transmitted mutations in the parkin gene, the detection of which also requires comprehensive screening for small mutations and exon rearrangements. Given these technical considerations and, more importantly, because of the different prognosis of the two conditions, a fast, inexpensive marker or tool would be helpful in establishing a diagnosis of neurodegenerative EOP vs nondegenerative DRD.To date, diagnostic approaches to distinguish between the two diseases with neuroimaging (CT and MRI) have not been successful. The more recent method of transcranial sonography (TCS) of the brain parenchyma may prove a promising alternative as an easily applicable and low-cost neuroimaging technique. The substantia nigra (SN) shows a distinct hyperechogenic pattern on TCS in about 90% of patients with Parkinson disease (PD) 5 that is associated with a significant reduction of 18 F-dopa uptake in the striatum and has been related to increased tissue concentrations of iron and loss of neuromelanin. Recently, SN hyperechogenicity has been described in symptomatic and asymptomatic carriers of parkin mutations. 6 There are no published data on TCS of the midbrain in patients with DRD.To determine whether TCS can detect differences in SN echogenicity in patients with DRD vs parkin-associated EOP, we studied 5 patients with genetically proven DRD (5 women, mean age 46.0 Ϯ 12.2 years, mean disease duration 31.0 Ϯ 13.8 years), 5 patients with EOP and homozygous or compound heterozygous parkin mutations (4 men, 1 woman, mean age 59.0 Ϯ 15.4 years, mean disease duration 12.3 Ϯ 6.3 years, mean Unified Parkin-son's Disease Rating Scale-III score ["on"] 23.0 Ϯ 15.3), and 10 healthy control subjects (5 men, 5 women, mean age 52.6 Ϯ 13.2 years). TCS examination was performed through the preauricular acoustic bone window, using a phased-array ultrasound system with a 2.5-MHz sector transducer (SONOS 5500; Philips Medical System, Best, the Netherlands). A standardized axial mesencephalic plane (landmark: butterfly-shaped brainstem) with a maximum depth of 12 cm from the temporal bone window on each side was used to localize the maximum extent of the hyperechogenic signals from the i...

British Society of Gastroenterology (BSG) guidelines for management of autoimmune hepatitis

“…Several cases of AIH have been associated with minocycline,27–31 interferon α,32–35 nitrofurantoin36–38 and, recently, with infliximab 39. There are anecdotal reports of associations with many other drugs including ezetimibe,40 interferon β,41 42 ornidazole,43 diclofenac,44 indomethecin,45 terbinafine,46 methyldopa,47 ranitidine,48 atorvastatin,49 fluvastatin,50 fibrates,51 adalimubab52 and after hepatitis A vaccination 53. AIH has also been reported after herbal medicines 54 55.…”

Autoimmune hepatitis after high-dose intravenous methylprednisolone pulse in RR-MS

“…If a sustained serum level of liver enzymes is still observed, an AIH screening should be performed. In a single case, AIH was found after interferon beta treatment for MS [3]. Particularly, AIH might occur in patients with multiple autoimmunity as an immune rebound phenomenon after immunosuppressive therapy regimens, as shown in two cases of patients with Hashimoto's thyreoditis [4] or Graves' ophthalmopathy [5] receiving MPT.…”

Suspected autoimmune hepatitis and primary biliary cirrhosis unmasked by interferon-beta in a multiple sclerosis patient

“…Although no HLA typing was performed on this patient, therefore conclusions on the patients' genetic predisposition to PBC cannot be made (Invernizzi et al, 2012). The exact mechanism behind the induction of autoimmunity by IFN-b in MS patients is unknown (Durelli et al, 1998;Pulicken et al, 2006). PBC may have remained subclinical, although fatigue was present in this patient, which, in hindsight could have also been related to PBC (Bhandari et al, 2011).…”

“…The use of IFN-b in MS is associated with autoimmune hepatitis (Durelli et al, 1998;Pulicken et al, 2006;Grieco et al, 2007), hepatotoxicity (Tremlett et al, 2004) and fulminant liver failure (Yoshida et al, 2001) and can occur years into treatment (Grieco et al, 2007). The use of IFN-b for MS has not been associated with unmasking PBC or precipitating de novo antimitochondrial antibodies (the classic serologic marker of PBC).…”