Immune disorders and rheumatologic manifestations of viral hepatitis

Table 1 Cases of vasculitis in hepatitis A

Case	Dan et al[21]	Press et al[22]	Nassih et al[23]	Chemli et al[24]	Mohan et al[25]	Altınkaynak et al[26]
Age, yr	30	2	8	10	< 1	10
Sex	Female	Female	Female	Male	Female	Male
Diagnosis	CNV	CNV	CGV	HSP	HSP	HSP
Body temperature	N	N/A	N	N/A	Mild fever	N
Time of the onset after the onset of hepatitis	2 wk	N/A	8 wk	3 d after admission to hospital	During the first month of illness	2 wk
Second wave of hepatitis	-	N/A	-	-	-	-
Pruritus	+	N/A	+	+	-	-
Jaundice	+	N/A	+	N/A	+	+
Rash	EPR over the hips, but also involving the buttocks and arms, and rare petechiae	Ecchymotic lesions	PP on the legs, forearms, and the back	PP on the declivous regions	Bluish PP on both lower limbs, swelling over dorsum of hands and feet	PP on the legs and on the gluteal regions.
Joints	N	N/A	Arthritis in the knees	Arthralgia	Arthritis in the right knee	Arthralgia
GN	No	N/A	Dipstick test was positive to proteins (2+) and blood (3+)	No	No	No
Gut	N	N/A	N	Abdominal pain	Small amount of blood in stool	Abdominal pain
RF	N/A	N/A	Negative	N/A	Negative	Negative
ANA	N/A	N/A	Negative	N/A	Negative	Negative
WBC, 109/L	6.3	N/A	7.2	N/A	↑	9.9
CRP, mg/L	N/A	N/A	38	N/A	N/A	N
Platelets, 109/L	408	N/A	N/A	N/A	N	416
ESR, mm/h	80	N/A	80	N/A	N/A	N/A
Cryoglobulins	N/A	N/A	IgM, IgA, and IgG	N/A	N/A	N/A
Transaminases	↑	N/A	↑	↑	↑	↑
Complement	N	N/A	N/A	N/A	N/A	N
Skin biopsy	LCV with deposition of IgM and C3	Necrotizing vasculitis with fibrin thrombi	LCV	N/A	LCV	N/A
Treatment	N/A	GC	GC	N/A	Analgetics	N/A

ANA: Antinuclear antibodies; CNV: Cutaneous necrotizing vasculitis; CRP: C-reactive protein; CGV: Cryoglobulinemic vasculitis; EPR: Erythematous papular rash; ESR: Erythrocyte sedimentation rate; GN: Glomerulonephritis; GC: Glucocorticoids; HSP: Henoch-Schonlein purpura; LCV: Leukocytoclastic vasculitis; N: Normal; N/A: No available; PP: Palpable purpura; RF: Rheumatoid factor.

Table 2 Cases of vasculitis in hepatitis A

Case	Garty et al[27]	Sasan et al[28]	Islek et al[29]	Islek et al[29]	Bozaykut et al[30]	Inman et al[12]	Inman et al[12]
Age, yr	8	8	13	11	< 1	26	26
Sex	Male	Male	Male	Female	Female	Female	Female
Diagnosis	HSP	HSP	HSP	HSP	CGV	CGV	CGV
Body temperature	N/A	37.2	N	N	N	N	N
Time of the onset after the onset of hepatitis	5 wk	5 wk	13 wk	5 wk	N/A	20 wk	19 wk
Second wave of hepatitis	-	-	+	+	N/A	+	+
Pruritus	-	-	-	+	-	-	-
Jaundice	-	-	-	+	-	+	-
Rash	PP on on the buttocks, penis and legs, which began with darkening of the right half of the scrotum	Non blanching red-brown papules over both thighs and legs	PP on the legs	PP on the legs	Oedema and ecchymosis on the dorsum of the hands and from feet to the knees	PP on on the legs, buttocks, arms, which began with ankles	No rash
Joint	N	Arthritis in the knees and ankles	Arthritis in the right knee and ankle	Arthritis in unspecified joints	N	Arthritis in the knees and ankles	Arthritis in the ankles, right fourth and fifth right metatarso-phalangeal joints
GN	No	No	No	No	No	No	No
Gut	N	Abdominal pain	Abdominal pain	Abdominal pain	N	N	N
RF	N/A	N/A	Negative	Negative	N/A	1:160	1:320
ANA	N/A	N/A	Negative	Negative	N/A	N/A	N/A
WBC, 109/L	N/A	10.1	4.6	7.2	12	N/A	N/A
CRP, mg/L	N/A	N/A	N	N/A	N/A	N/A	N/A
Platelets, 109/L	N/A	516	250	407	300	N/A	N/A
ESR, mm/h	N/A	34	22	42	N/A	N/A	N/A
Cryoglobulins	N/A	N/A	N/A	N/A	Positive	Anti-HAV IgG	Anti-HAV IgG
Transaminases	↑	N	↑	↑	N	↑	↑
Complement	N/A	N/A	N	C3↑, C4 - N	N	N/A	N/A
Skin biopsy	N/A	N/A	LCV with deposition of IgM in the dermo-epidermal junction	LCV	LCV	LCV	N/A
Treatment	N/A	GC	Sympto-matically	N/A	No	No	NSAID

ANA: Antinuclear antibodies; CRP: C-reactive protein; CGV: Cryoglobulinemic vasculitis; ESR: Erythrocyte sedimentation rate; GN: Glomerulonephritis; GC: Glucocorticoids; HSP: Henoch-schonlein purpura; LCV: Leukocytoclastic vasculitis; N: Normal; N/A: No available; NSAID: Nonsteroidal anti-inflammatory drugs; PP: Palpable purpura; RF: Rheumatoid factor.

Table 3 Differential diagnosis of vasculitis in hepatitis C viruses-infection (modification from[102])

	Cryoglobulinemic vasculitis	Polyarteritis nodosa
Weight loss	+/-	+++
Fever	-	++
Myalgia	+	++
Polyneuropathy	+++	++
Mononeuritis multiplex	+	+++
Livedo	+/-	++
Arterial hypertension	++	+++
Orchitis	-	+
Abdominal pain	+/-	++
Diarrhea	-	+
Intestinal bleeding	-	+
Microaneurysms or stenosis	-	+++
C-reactive protein level	Normal	↑

Table 4 Cases of arthritis in hepatitis E

Case	Al-Shukri et al[110]	Serratrice et al[111]
Age	52	51
Sex	Female	Female
Joints	Shoulders, elbows, hips, knees, ankles, left second and third metacarpophalangeal	Ankles and knees followed by the wrists and fingers
Duration of arthritis	No data	3 mo
Rash	Maculopapular, non-itchy rash all over her body	No
Fever	No	No
Jaundice	No	No
Pruritus	No	No
Other symptoms and signs	Retroorbital pain, eye discharge, headache, and loss of appetite	No
Rheumatoid factor	No	No
Antinuclear antibodies	No	No
White blood cells, 109/L	Normal	2.8
Erythrocyte sedimentation rate, mm/h	35	24
C-reactive protein, mg/L	25	3
Transaminases	↑	↑
Complement	C3 - ↑; C4 -Normal	No data
Treatment	No data	No specific treatment

Table 5 A summary of the main immunological and rheumatologic manifestation in viral hepatitis

	Hepatitis A	Hepatitis B	Hepatitis C	Hepatitis E
Rheumatoid factor	Only 2 cases	Approximately 12% of patients	15% of patients	1 case in a patient without transplant
Antinuclear antibodies	In a case of lupus-like reaction and some cases of AIH triggered by HAV infection	Approximately 25% of patients	20%-30% of patients	9%-37% (acute) and 24% (chronic) of patients
Cryoglobulins	95% of patients in 1 study	2% of patients	65% of patients	7% (acute) and 27% (chronic) of patients
Arthralgia	10%-20% of patients	3% of patients	42% of patients	Approximately 60% of patients
Arthritis	Only in patients with vasculitis (7 cases)	About a quarter of patients with pain in joints	5%-10% of patients	2 cases
GN	4 cases of mesangio-proliferative GN	3% of GN: membranous GN (40%); membrano-proliferative GN (20%); focal segmental glomerulo-sclerosis (20%); mesangio-proliferative GN (10%), others (10%)	Approximately 50% of GN: membranous GN (5%); membrano-proliferative GN (55%); focal segmental glomerulo-sclerosis (25%); mesangio-proliferative GN (20%), others (5%)	1 case of membrano-proliferative GN; some cases of GN after transplantation
Henoch-Schonlein purpura	7 cases	Some cases	Some cases	1 case
CGV	4 cases	10% of non-HCV CGV cases	90%-95% of CGV cases	Some cases
PAN	No cases	35% of PAN cases	20% of PAN cases	No cases
Uveitis	Some cases	2% of patients	Some cases	No cases
AIH	11 cases	55% of AIH cases	Very rare	No cases
PBC	1 case of overlap syndrome	40% of PBC cases	Approximately 10% of PBC cases	No cases

AIH: Autoimmune hepatitis; CGV: Cryoglobulinemic vasculitis; GN: Glomerulonephritis; HCV: Hepatitis C viruses; PAN: Polyarteritis nodosa; PBC: Primary biliary cholangitis.