2.2 Method (Differential diagnosis, investigation, and treatment)
Baseline investigations revealed normocytic, normochromic anaemia with leukocytosis (Hb=10.4mg/dL, MCV=98.5fL, TLC=17). His ESR and CRP levels were elevated at 80 mm/hr and 23 mg/L (normal ESR= <20 mm/hr, CRP= <10 mg/L), respectively. His serum calcium levels were slightly decreased at 8.3mg/dL (8.5-10.3 mg/dL). The rest of the biochemistry analyses were normal. His LFTs revealed an elevated SGPT value of 106 U/L (7-56 U/L), decreased albumin of 3.0 g/dL (3.4-5.4 g/dL) and elevated globulin level of 4.2 g/dL (2.0-3.5 g/dL). His coagulation profile is normal. His Lipid profile showed a decreased HDL level of 16 mg/dL (40-60 mg/dL). His urine D/R was normal. His blood and urine cultures were negative for any growth. His abdominal ultrasound revealed no abnormalities. Doppler ultrasound of both upper limbs was normal. Doppler ultrasound of the left posterior tibial artery showed biphasic spectrum, normal peak systolic velocity and bilateral dorsal pedis, and the right posterior tibial arteries showed monophasic spectrum and normal peak systolic velocities. His transthoracic echocardiography didn’t reveal any abnormalities. He tested positive for ANA with an antibody titre of 1:240. His ENA profile was negative, and his anti-dsDNA was normal. His serum c-ANCA came out to be positive at 9.56. His serum ACE and IgE levels were not elevated. His LDH levels were 397 U/L (140-280 U/L), and uric acid levels were 2.0 mg/dL (3.5-7.2 mg/dL). His HbA1c was normal at 5.3%, TSH was at 2.58 mIU/L (0.5-5.0 mIU/L), and anti-CCP was negative (6.6 EU/mL, negative at <20 EU/mL). All the viral markers were negative except for hepatitis B PCR, which was positive and revealed a quantity of 3040 IU/mL. Hepatitis D PCR was negative. His endoscopy revealed diffuse candidiasis and mild pancreatitis. Fibroscan showed normal-mild fibrosis (F1) with a mean metavir score of 7.0 kPa.
After extensive testing and multiple opinions from different departments ( dermatology, nephrology), a diagnosis of C-ANCA-associated small vessel vasculitis secondary to Hepatitis B was made.
Treatment started with 1g of Methylprednisolone for five days, followed by a low dose of 40 mg/day divided dose of prednisolone, which was tapered off gradually. The patient’s lesions improved with this therapy. After tapering off steroids, 50 mg of azathioprine 2-4 mg/kg was added.
3.DISCUSSION:
Hepatitis B virus (HBV) infection exhibits varied clinical manifestations, influenced by factors such as the patient’s age, immune response during infection, and the timing of disease detection. Chronic HBV infection is notably prevalent worldwide, with an estimated 360 million individuals persistently infected. Tragically, HBV-related liver diseases, including hepatocellular carcinoma, claim approximately 600,000 lives annually (4). hepatitis B virus (HBV) infection has complex clinical implications which remain unclear, particularly regarding its role in autoimmune-mediated vasculitis. Vasculitis is the most severe but uncommon extrahepatic manifestation of HBV infection. Vasculitis associated with HBV infection are Polyarteritis nodosa, Cryoglobulinemic Vasculitis and Leukocytoclastic Vasculitis (5). Polyarteritis nodosa (PAN) is the most dramatic manifestation of primary HBV infection(6). General symptoms of PAN include fever, weakness, fatigue, reduced appetite, and weight loss. Skin manifestations can vary from palpable purpura to nodules and red rashes. Multiple studies have reported that patients treated with interferon have experienced clinical improvement and remission of PAN.(7)
However, our case presented cANCA associated with vasculitis secondary to hepatitis B as the initial manifestation of chronic HBV infection. The presence of the cANCA is a significant diagnostic marker for many small-vessel vasculitis, including granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis. These conditions are commonly grouped under ”antineutrophil cytoplasmic antibody-associated vasculitis” (AAV). (8) HBV is notably linked with PAN and, to a lesser extent, cryoglobulinemic vasculitis. There are cases where HBV triggers antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), affecting blood vessel health in diverse ways. Still, the exact pathophysiological mechanisms underlying these associations remain a subject of ongoing research (5). Only three cases have been reported in the literature to date. (Table 1)
According to Turan et al., there is a notable prevalence of ANCA in Patients diagnosed with Chronic hepatitis B(CHB). Therefore, Patients diagnosed with CHB should undergo evaluation, focusing on C-ANCA and PR3-ANCA, especially when presenting with vasculitis symptoms and lesions. The relationship between ANCA and vasculitis or other immune-related conditions in CHB patients remains controversial. Additionally, it’s crucial to ascertain whether HBV induces ANCA production independently or if some underlying immune-related symptoms mimicking vasculitis are present. (9)
Management of patients these patients presents a unique challenge; however, these patients have shown positive responses to steroid therapy; however, for patients with coexisting conditions, steroids should be administered alongside antiviral therapy to decrease immune complex reaction and viral load, respectively [10]