Overlap collagen vascular disease as a marker for development of primary biliary cirrhosis

A 27-year-old black male presented with a 4 month history of polyarthritis and recurrent low grade fever. Laboratory findings revealed mild anemia, leukopenia, and thrombocytopenia (RBC 4.02 (4.70–6.10 m/UL), WBC 3.7 (4–11 K/UL), Platelets 130 (150–450 K/UL). Chemistries showed elevated total protein 9.7 (6.3–8.3) with normal albumin, alpha-1, alpha-2, and beta globulin levels and elevated gamma globulin levels 2.63 (0.64–1.17 G/DL), elevated aspartate aminotransferase (AST) 71 (17–49 U/L), alanine aminotransferase (ALT) 137 (7–56 U/L), lactate dehydrogenase (LDH) 629 (313–618 U/L) with normal creatinine phosphokinase, alkaline phosphatase, and bilrubin, elevated triglycerides 243 (35–160 MG/DL), decreased HDL 29 (34–65 MG/DL), elevated very low density lipoprotein (VLDL) 49 (0–40 MG/DL). Hepatitis screen was negative. Over the next 4 months, the patient developed cold-induced, vasospastic attacks consisting of blanching and pallor of the digits, followed by cyanosis and later hyperemia and erythema; consistent with Raynaud's syndrome (RS). Shortly thereafter the patient developed painful digital subungual skin lesions, as well as nailfold ulcerations. At approximately the same time the patient also reported increasing gastro-esophageal reflux, which was confirmed with a barium swallow. However, endoscopic examination and biopsies showed no evidence of Barrett's esophagus. The patient failed to return to his internist and gastroenterologist after the above evaluations. Three to 4 months later the patient presented to dermatology. In addition to his original lesions, the patient had developed lesions within the ear and on the extensor surfaces of his arms and legs, most prominent around his elbows and knees. The cutaneous physical examinations showed subungual hyperkeratotic lesions forming a ventral ptreygium (Fig. 1a). The nail folds showed some erosions and nailfold. Capilloscopy showed loss of the total number of capillary structures and normal micro-vessel pattern at the edge of the proximal nailfold with enlargement of the remaining capillaries. The nails showed ragged cuticles, and splinter hemorrhages were present in some nails (Fig. 1b). Both ears showed markedly hyperkeratotic lesions with follicular plugging, and the patient had hyperkeratotic lesions on the extensor surfaces of all the extremities (Figs 2a,b and 3). Figure 1. (a) Subungual keratoses forming a ventral ptyregium present on the majority of fingers. (b) The nails showed ragged cuticles, and splinter hemorrhages were present in some nails Download figure to PowerPoint Figure 2. (a, b) Hyperkeratotic lesions involving ears with follicular plugging Download figure to PowerPoint Figure 3. Hyperkeratotic lesions on the extensor surfaces of all the extremities Download figure to PowerPoint Laboratory findings at that time showed continued mild anemia, leukopenia, and thrombocytopenia. Serum chemistries showed only elevation of ALT 68 U/L, with continued elevation of the gamma globulin fraction of total proteins. The lipid profile was within normal limits as were thyroid functions including free T4 and thyroid stimulating hormone (TSH), and HIV-1 screen was negative. The antinuclear antibody (ANA) was positive, > 1 : 1280 with a centromere pattern. Extractable nuclear antigen (ENA) was positive; anti-Smith 2.16 (nl > 1.1); anti-RNP 2.59 (nl > 1.1); anti-SSA 5.68 (nl > 1.1); anti-SSB 1.92 (nl 0.89–1.09); Anti-ribosomal P antibody 60 (low positive 1.2–2.5, high positive > 5.0). Anti-SCL-70, anti-JO1, anti-DNA, Rheumatoid factor, antihistone, and anticardiolipin IGG, IGM, and IGA were negative. Additional studies showed anti-centromere antibodies (AMAs) to be elevated 1 : 480 (nl 400 high risk for development of primary biliary cirrhosis [PBC]). Two biopsies from extremity lesions both showed features of lupus erythematosus (LE), including hyperkeratosis, follicular plugging, with interface and hydropic changes in the basal cell layer and a perivascular and periadnexal lymphoplasmacytic infiltrate and increased dermal mucin (Fig. 4). Figure 4. Biopsy specimen showing hyperkeratosis, follicular plugging, with interface and hydropic changes in the basal cell layer and a perivascular and periadnexal lymphoplasmacytic infiltrate and increased dermal mucin 30× Download figure to PowerPoint Although the patient did return for follow-up after his initial dermatology visit, he failed to keep subsequent appointments and his rheumatology referral. Approximately 12 months later the patient was located. The patient had subsequently developed liver enzyme abnormalities and had a biopsy showing features of primary biliary cirrhosis (PBC). At the time of this follow up, the patient was being treated with ursodeoxycholic acid, and he reported no significant change in his cutaneous disease.