Arteriovenous Haemangioma in Chronic Liver Disease: Clinical and Histopathological Features of Four Cases

Akiyama M, Inamoto N
Br J Dermatol. 2001;144:604-609

Chronic liver diseases are known to cause several skin manifestations, including cutaneous vascular changes such as spider naevus and palmar erythema. Arteriovenous haemangioma (AVH), a benign acquired cutaneous vascular lesion, has also been reported to be associated with chronic liver disease. We report here four cases of AVH in patients with chronic liver disease: (i) a 59-year-old man who had suffered from chronic active hepatitis associated with hepatitis C virus for 15 years; (ii) a 48-year-old man who had suffered from alcoholic hepatitis for 3 years and was diagnosed with liver cirrhosis 1 year ago; (iii) a 69-year-old female who had had chronic active hepatitis associated with hepatitis C virus infection for 20 years and was diagnosed with liver cirrhosis 7 years ago; and (iv) a 48-year-old man who had had chronic active hepatitis associated with hepatitis B virus infection for about 20 years. All patients showed an asymptomatic solitary dome-shaped reddish papule, 5-10 mm in diameter, on the face (first, second and third patients) or chest (fourth patient). Histopathological examination of the tumours revealed features of AVH, namely a well-circumscribed lesion composed of vascular structures of various sizes reminiscent of arteries and veins. In all four cases, elastic-van Gieson stain showed the absence of an internal elastic lamina in the thick-walled vessels as well as the thin-walled vessels. Examination of multiple sections demonstrated glomus cells and an ascending artery feeding the tumour vessels in only one case. Slight inflammatory cell infiltration was seen in the stroma of three patients while Toluidine blue staining revealed an increased number of mast cells in the stroma in all lesions. The present cases suggest that the occurrence of AVH associated with chronic liver disease is not related to any specific liver disease, but may be related to chronic liver dysfunction itself.

Extrahepatic Manifestations of Chronic Viral Hepatitis

Pyrsopoulos NT, Reddy K.
Curr Gastroenterol Rep. 2001;3:71-78

Hepatitis B (HBV) and C (HCV) viruses are well-recognized causes for chronic hepatitis, cirrhosis, and even for hepatocellular carcinoma. Apart from liver disease, these viral infections are known to be associated with a spectrum of extrahepatic manifestations. The prevalence of clinically significant extrahepatic manifestations is relatively low, but it can be associated with significant morbidity and even mortality. An awareness and recognition of these manifestations is of paramount importance in facilitating early diagnosis and in offering treatment. However, treatments are not necessarily effective, and patients may continue with disabling extrahepatic manifestations. Hepatitis B virus has been well recognized as causing a variety of manifestations that include skin rash, arthritis, arthralgia, glomerulonephritis, polyarteritis nodosa, and papular acrodermatitis. More recently, infection with hepatitis C virus has elicited considerable interest for its role in a spectrum of extrahepatic manifestations. Among the best-reported are cryoglobulinemia, glomerulonephritis, high titer of autoantibodies, idiopathic thrombocytopenic purpura, lichen planus, Mooren's corneal ulcer, Sjogren's syndrome, porphyria cutanea tarda, and necrotizing cutaneous vasculitis. The precise pathogenesis of these extrahepatic complications has not been determined, although the majority represent the clinical expression of autoimmune phenomena.

Ranitidine-related Stevens-Johnson Syndrome in Patients With Severe Liver Diseases: A Report of Two Cases

Lin CC, Wu JC, Huang DF, et al
J Gastroenterol Hepatol. 2001;16:481-483

Ranitidine is widely used and well tolerated. Ranitidine-related skin eruption is rare and usually mild. We presented two patients who developed Stevens-Johnson syndrome after ranitidine therapy. Before therapy, both patients had severe liver disease and jaundice. The first was a case of ketoconazole-induced hepatitis, and the second was a case of hepatitis C-related liver cirrhosis with hepatocellular carcinoma. Ranitidine was the most likely drug responsible for causing Stevens-Johnson syndrome in these two patients.

Manifestation of Cutaneous Polyarteritis Nodosa During Interferon Therapy for Chronic Hepatitis C Associated With Primary Biliary Cirrhosis

Dohmen K, Miyamoto Y, Irie K, Takeshita T, Ishibashi H
J Gastroenterol. 2000;35:789-793

Interferon alpha-2b was administered to a 50-year-old Japanese woman with chronic hepatitis C associated with primary biliary cirrhosis. Two months after the beginning of the interferon alpha-2b therapy a systemic nodular, erythematous rash developed. Histological analysis of the skin revealed typical features of necrotizing arteritis. Because there was no microhematuria, and no microaneurysms were detected on abdominal angiography, a diagnosis of cutaneous polyarteritis nodosa was made. A good outcome was achieved after interferon alpha-2b was discontinued and prednisolone was administered instead. The cutaneous polyarteritis nodosa in this patient is thus considered to have occurred as an adverse effect of interferon administration. To our knowledge, this is the first reported case of cutaneous polyarteritis nodosa which developed because of interferon therapy for chronic hepatitis C associated with primary biliary cirrhosis.

Synchronous Development of Disseminated Superficial Porokeratosis and Hepatitis C Virus-related Hepatocellular Carcinoma

Kono T, Kobayashi H, Ishii M, Nishiguchi S, Taniguchi S
J Am Acad Dermatol. 2000;43:966-968

Immunosuppression and transplantation have been reported to induce porokeratosis (PK), especially its variant, disseminated superficial PK (DSP). On the other hand, there is ample evidence of a relationship between hepatitis C virus (HCV) infection, liver cirrhosis (LC), and hepatocellular carcinoma (HCC). We report 3 cases of DSP in which the outbreak of DSP was suspected to have occurred during the development of HCC in patients with HCV-positive LC. The patients had undergone ultrasonographic study regularly, and no signs of malignancy had been found before the development of DSP. Their outbreaks of DSP were very acute, and the period between the development of DSP and diagnosis of HCC ranged from 2 to 6 months. The association of HCV-related HCC and DSP has never been previously reported. HCV-induced immunomodulation or its effect on the p53 system may be the basis for this type of association. It is necessary to consider development of HCC whenever DSP is found in HCV-positive patients. DSP may be a new paraneoplastic dermadrome.

Capillaritis Associated With Interferon-alfa Treatment of Chronic Hepatitis C Infection

Gupta G, Holmes SC, Spence E, Mills PR
J Am Acad Dermatol. 2000;43:937-8

We report the case of a 36-year-old man who was referred with an asymptomatic eruption that started on both lower legs. This started shortly after being commenced on interferon-alfa for chronic hepatitis secondary to hepatitis C. Clinically, the eruption was consistent with a capillaritis (pigmented purpuric dermatosis). Histology confirmed this to be lymphocytic vasculitis. Lymphocytic vasculitis is frequently identified in the salivary glands of patients who are hepatitis C positive. Although leukocytoclastic vasculitis confined to the skin is frequently reported with hepatitis C, lymphocytic vasculitis is rarely reported. We consider that the lymphocytic vasculitis in our patient occurred as a result of interferon-alfa treatment because of the strong temporal relationship between the onset of the skin eruption and drug therapy.

Chronic Hepatitis C Virus Infection Associated With a Generalized Granuloma Annulare

Granel B, Serratrice J, Rey J, et al
J Am Acad Dermatol. 2000;43:918-919

We report the first case of generalized granuloma annulare occurring in a 65-year-old woman who was chronically infected with hepatitis C virus. Granuloma annulare totally regressed during alpha-interferon treatment. As chronic hepatitis C virus infection is frequent, a serodiagnosis would be of interest in patients who have generalized granuloma annulare. A link between these 2 diseases may be strongly suspected.

Previous Tuberculosis, Hepatitis C Virus and Lichen Planus. A Report of 10 Cases, A Causal or Casual Link?

Pellicano R, Palmas F, Leone N, et al
Panminerva Med. 2000;42:77-81

We report 10 cases of lichen planus (LP) and chronic liver disease linked to HCV. The mean age was 63.4 +/- 5.1 years (range 51-73), five were female; six patients had an established cirrhosis of the liver, as shown by either a liver biopsy or the ultrasonographic and biohumoral evidence. The remaining four patients had chronic hepatitis. Histological examination confirmed the presence of LP: the localization of the dermatosis was restricted to the skin in four patients, to the mucous membranes in five (4 atrophic erosive and one erosive) while the remaining had mucous-cutaneous localization. A type II cryoglobulinemia was demonstrated in two and a type III in one of the patients, while no one had otherwise circulating autoantibodies (anti-nuclear, anti-smooth muscle, anti-liver kidney microsomal type 1 and anti-mitochondrial antigens) such as other etiological factors of liver disease. In six of the patients the history was positive for previous Mycobacterium tuberculosis infection. In clinical practice the patients with chronic liver disease and HCV infection can also suffer from severe extrahepatic manifestations, including lichen planus.

Necrolytic Acral Erythema Associated With Hepatitis C: Effective Treatment With Interferon Alfa and Zinc

Khanna VJ, Shieh S, Benjamin J, et al
Arch Dermatol. 2000;136:755-757

Background: Necrolytic acral erythema is a recently described necrolytic erythema that is unique in its exclusive acral location and strong association with hepatitis C.
Observation: We report the first case of necrolytic acral erythema in the United States. The patient is a 43-year-old black woman who presented with a 4-year history of tender, flaccid blisters localized to the dorsal aspect of her feet. Serum zinc and glucagon levels were normal. Serum antibodies were positive for hepatitis C, and a liver biopsy specimen showed chronic hepatitis. She was successfully treated with interferon alfa-2b and zinc. We review all previously reported cases.
Conclusions: Necrolytic acral erythema is a distinct entity. In a review of the literature, most patients were between 35 and 55 years of age, although 1 patient was 12 years old. Five of 8 patients were female. Four of 7 patients described previously were treated with variable success using oral zinc sulfate and amino acids, whereas 2 were successfully treated with interferon alfa. All patients were infected with hepatitis C. Necrolytic acral erythema appears to be a skin disorder linked to infection with hepatitis C virus that responds to treatment with interferon alfa and oral zinc.

Multifactorial Thrombotic-type Microangiopathy With Skin Ulcers and Hepatitis C Infection

Hernandez JL, Zarrabeitia R, Fernandez-Llaca H, Hortal L, Gonzalez-Macias J
Eur J Intern Med. 2000;11:165-167

The case of a patient with hepatitis C virus infection who presented with symmetric ulcers of the legs is reported. She was found to have type III mixed cryoglobulinemia, high titers of anticardiolipin antibodies, lupus anticoagulant, and a free protein S deficiency. To our knowledge, this is the first reported case of such an association. The role of these factors in the pathogenesis of skin lesions in the setting of hepatitis C virus infection is discussed.

Cutaneous Disorders Associated With Hepatitis C Virus Infection

Cordel N, Chosidow O, Frances C
Ann Med Interne (Paris). 2000;151:46-52

Since the discovery of hepatitis C virus (HCV) in 1989, many cutaneous disorders have been observed in patients suffering from chronic HCV infection. The relationship between HCV infection and cryoglobulinemia or porphyria cutanea tarda (PCT) is now clearly established, but the link between HCV and other dermatoses is still controversial. This review of the main dermatologic disorders, directly or indirectly related to HCV infection, lead to conclude that HCV markers have to be investigated systematically in case of cryoglobulinemia, PCT or pruritus. In other dermatologic disorders, HCV serology will be necessary only in case of risk factors for HCV infection, or presence of abnormal liver function tests.

Coexistence of Psoriasis and Linear IgA Bullous Dermatosis

Takagi Y, Sawada S, Yamauchi M, Amagai M, Niimura M
Br J Dermatol. 2000;142:513-516

Linear IgA bullous dermatosis (LABD) is characterized by IgA autoantibodies against components of the basement membrane zone (BMZ). A 97-kDa protein is one of the major autoantigens associated with this disease. We report a 68-year-old man who developed LABD after a 3-year history of psoriasis and in the context of active hepatitis C virus infection. He had been treated with cyclosporin for psoriasis for about 9 months. Histologically, there was a subepidermal blister containing neutrophils and eosinophils with lymphocytes infiltrating predominantly in the dermis. Direct immunofluorescent staining showed linear IgA deposition at the BMZ. The patient's IgA autoantibodies bound exclusively to the epidermal side of 1 mol/L salt-split normal human skin. Immunoblot analysis identified a 97-kDa autoantigen in epidermal extracts. This appears to be the first case of LABD with IgA autoantibodies against a 97-kDa autoantigen, associated with psoriasis and hepatitis C virus infection.

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