Pruritic rash as a clue to organ dysfunction

A previously well 18-month-old girl presented to a regional hospital in New South Wales with a 3-week history of a generalised rash. The rash was pruritic, erythematous, maculopapular and found on the forehead, ear lobes, torso, arms, legs and feet (Fig. 1). There was no history of fever, systemic symptoms or medication. Differential diagnoses of papular urticaria due to insect bites, infected atopic dermatitis and scabies were considered.1 The lesions were swabbed for bacteria and viruses and she was commenced on topical steroids (betamethasone propionate and methylprednisolone aceponate), moisturiser, flucloxacillin and cetirizine, followed by topical application of permethrin. As no improvement was noted few weeks after starting treatment, we investigated her for systemic causes of pruritus including renal and hepatobiliary disease, thyrotoxicosis and a myeloproliferative disorder like Hodgkin's lymphoma.1 Results revealed normal full blood count, blood picture, renal, thyroid functions and total serum IgE. Liver function tests showed elevated alanine aminotransferase (530 U/L), aspartate transaminase (224 U/L) and bile acid (>180 μmol/L) and normal bilirubin (6 μmol/L), gamma-glutamyl transferase (GGT) (12 U/L), albumin (36 g/L) and prothrombin time. Further investigations exploring a liver pathology found negative hepatitis A, B, C and cytomegalovirus serology and normal anti nuclear antibodies (ANA), anti-dsDNA, serum copper, caeruloplasmin and alpha 1 antitrypsin genotype. Abdominal ultrasonography showed normal liver and biliary tree. As initial investigations showed deranged liver functions we did not proceed to do a skin biopsy. Elevated transaminases (alanine aminotransferase and aspartate transaminase) and bile acids with normal GGT suggested the possibility of low GGT intrahepatic cholestasis and the patient was referred to the gastroenterology unit at a tertiary hospital. Diagnoses of benign recurrent intrahepatic cholestasis (BRIC) and progressive familial intrahepatic cholestasis (PFIC), the two important conditions with low GGT, were considered by the tertiary team and cholestasis gene panel was performed. The genetic studies identified two heterozygous variants in the ATP8B1 gene which is associated with BRIC1/PFIC1. Patient was first treated with ursodeoxycholic acid, cholestyramine and rifampicin with poor response. Subsequently a remarkable response was noted with ileal bile acid transport inhibitor (ILBT) odevixibat. The pruritus resolved in a few days and the rash healed in 1 week. Over the following 2 years she experienced three episodes of intrahepatic cholestasis triggered by acute diarrhoeal illness. Each episode lasted a few weeks and responded well to odevixibat. Informed written consent was obtained from parents for publication of case details and photographs. All clinical information and photographs are deidentified, and parents are fully informed of benefits and risks, complying with good ethical practice of the institution. Guidelines in CARE Flowchart for case reports have been followed in preparation of the manuscript. BRIC1 and PFIC1 are two rare genetic disorders causing low GGT intrahepatic cholestasis. Both conditions are caused by pathogenic variant of ATPB81 gene found in chromosome 18 q 21–22. Although autosomal recessive heterozygosity could cause disease. This genetic mutation leads to defective bile salt excretion.2 BRIC1 is characterised by intermittent attacks of cholestasis which can start at any age and may last for several weeks or months. In between episodes the patient is asymptomatic with normal liver functions and the liver structure is preserved.3 Clinically distinct PFIC1 is characterised by severe cholestasis starting before 12 months, progressing to cirrhosis and liver failure.2 Our patients presentation and clinical course with recurrent episodes of cholestasis beginning at 18 months of age with normality in between attacks makes BRIC the most likely diagnosis. A few case reports of children with BRIC1 progressing to develop severe cholestasis are found in literature, emphasising that close monitoring of our patient is required.4 The most distressing symptom of BRIC1 is the pruritus and rash. Treatment with synthetic bile acid (ursodeoxycholic acid), bile acid resins (cholestyramine) rifampicin and new ILBT agents like odevixitab could be helpful.