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]