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Necrolytic migratory erythema without glucagonoma associated with hepatitis B

European Journal of Dermatology. Volume 15, Number 1, 49-51, January-February 2005, Clinical report

Summary

Author(s) : Yohei Kitamura, Madoka Sato, Atsushi Hatamochi, Soji Yamazaki , Department of Dermatology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan Fax : (+81) 282 86 3470..

Summary : We report a case of necrolytic migratory erythema (NME) without glucagonoma associated with hepatitis B. Although the most common cause of NME is a glucagon-secreting α-islet cell tumor of the pancreas, a dermatitis clinically and histologicaly identical to NME has been described in patients without glucagonoma. Impairment of hepatic dysfunction has been identified in the majority of them. However, NME associated with hepatitis B has never been reported in the literature. NME belongs to the family of necrolytic erythemas that share similar clinical and histologic findings. The terms used to describe NME and related conditions in the medical literature are confused. We added some discussion on the terminology of this disease.

Keywords : necrolytic migratory erythema, hepatitis B, zinc deficiency

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ARTICLE

Auteur(s) :, Yohei Kitamura, Madoka Sato^*, Atsushi Hatamochi, Soji Yamazaki

Department of Dermatology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan Fax : (+81) 282 86 3470.

accepté le 20 Juin 2004

Necrolytic migratory erythema (NME) is the cutaneous manifestation which occurs in patients with glucagonoma syndrome, i.e., glucagon-secreting α-islet cell tumor of the pancreas [1]. Less often, NME occurs in patients without glucagonoma. Among them, liver diseases are the most common associated conditions [2]. Recently, necrolytic acral erythema has been described as a distinct entity characterized by its acral distribution and association with hepatitis C virus [3]. We report a case of NME associated with hepatitis B.

Case report

A 53-year-old Japanese man was admitted to our department in August 2003 with a 2-month history of pruritic skin lesions. This dermatitis was rapidly exacerbated by his scratching several days before admission. On physical examination, the patient was a thin man with a body mass index of 18.6. He mentioned that he lived alone and had a diet composed primarily of alcohol and meat. He was noted to have a dusky, scaling, erosive dermatitis involving his fingers and soles (( figure 1 )A). A large well-demarcated crusted plaque was noted on his left lower limb (( figure 1 )B). Several psoriasiform eruptions with peripheral scaling were present on his legs.

Laboratory studies revealed elevated serum aspartate aminotransferase (81 U/l [normal, 10 to 37]), alanine aminotransferase (45 U/l [normal 3 to 34]), γ-glutamyl transpeptidase (101 U/l [normal, 18 to 66]), total bilirubin (1.8 mg/dl, [normal, 0.1 to 1.0]) and decreased serum levels of albumin (3.1 mg/dl [normal, 4.0 to 5.2]), total cholesterol (117 mg/dl [normal, 120 to 260]), and zinc (45 μg/dl [normal, 61 to 121]). Platelet count was 73 × 10⁹/l (normal, 163 to 428). He had a hyperchromic macrocytic anemia with decreased level of folic acid (1.2 ng/ml [normal, 3.6 to 12.9]). Serum glucagon level was normal.

Evaluation of his hepatitis serological status confirmed that he was positive for hepatitis B surface antigen, hepatitis B e antigen and antibody. Hepatitis B core antibody was highly positive. Antihepatitis C antibodies were not detected. He was considered a chronic asymptomatic hepatitis B carrier.

An abdominal computed tomographic scan failed to reveal either a pancreatic neoplasm or a hepatic mass.

A biopsy specimen taken from a crusted plaque on his left lower limb showed hyperkeratosis, parakeratosis and focal necrotic keratinocytes in the upper stratum spinosum and inflammatory infiltrates into the epidermis. Moderate superficial perivascular infiltrates of lymphocytes are present in the papillary dermis (( figure 2 )A). Psoriasiform erythema on the thigh revealed areas of epidermal necrosis, in which the upper layers of the epidermis showed abrupt necrosis, and pallor keratinocytes, some of which showed balloon-like cytoplasm (( figure 2 )B).

After hospitalization, his dermatitis promptly resolved with emollients and the levels of liver function tests, platelet count and serum zinc concentration were normalized.

Discussion

Wilkinson [4] introduced the term “necrolytic migratory erythema” to describe the rash which was associated with pancreatic glucagon-secreting α-islet cell tumors. The lesions are characterized by erythematous scaling, exudative, or eroded dermatitis which involves the central part of the face, perineum, and distal extremities. The rash is related to trauma in some areas [5].

NME belongs to the family of necrolytic erythemas that include acrodermatitis enteropathica, pellagra, essential fatty acid deficiencies, and recently described necrolytic acral erythema [3]. These entities share similar clinical and histologic findings. Acrodermatitis enteropathica is related to zinc deficiency. The autosomal recessive inherited form of acrodermatitis enteropathica is suggested to be caused by a mutation in the gene encoding an intestinal zinc transporter of the ZIP family, SLC39A4 [6]. Acquired zinc deficiency dermatosis presents at any age due to a variety of underlying disorders including dietary factors (anorexia nervosa, alcoholism, parenteral nutrition without zinc supplementation), gastrointestinal diseases and liver diseases [6–9]. Patients with NME are reported to have zinc deficiency [2, 5]. Our case also had zinc deficiency. Our patient had a dietary problem in addition to the hepatitic dysfunction, and both of them might lead to a negative zinc balance. There is no definition to differentiate acquired acrodermatitis enteropathica from non-glucagonoma- associated NME. These entities may be similar in etiology. We used the term “necrolytic migratory erythema” in the title because the term “acquired acrodermatitis enteropathica” gives the impression that zinc deficiency is the primary event of the dermatitis, contrary to the fact that several factors have been discussed in relation to the etiology of this dermatitis [5].

Necrolytic acral erythema is characterized by its exclusive acral distribution of lesions and association with hepatitis C infection [4]. This term is too restrictive as an entity and necrolytic acral erythema may belong to the spectrum of NME. NME without glucagonoma is commonly associated with impaired hepatic function, however, association of viral infection has never been discussed except the cases reported as necrolytic acral erythema. Our patient represents the first case of NME with hepatitis B infection. Hepatitis viruses may be causative factors of NME.

The pathogenesis of NME is still unknown. Although zinc deficiency may contribute to the etiology, many patients are reported to have a normal zinc concentration [5]. Kasper et al. [10] speculate that an abnormality in hepatic metabolism is responsible for the dermatitis. The case presented herein further supports this speculation. We should increase the awareness of the relationship between skin disease and liver disease.

References

1 Johnson SM, Smoller BR, Lamps LM, Horn TD. Necrolytic migratory erythema as the only presenting sign of a glucagonoma. J Am Acad Dermatol 2003; 49: 325-8.

2 Marinkovich MP, Botella R, Datloff J, Sangueza OP. Necrolytic migratory erythema without glucagonoma in patients with liver disease. J Am Acad Dermatol 1995; 32: 604-9.

3 Khanna VJ, Shieh S, Benjamin J, Somach S, Zaim MT, Dorner Jr. W, Shill M, Wood GS. Necrolytic acral erythema associated with hepatitis C. Arch Dermatol 2000; 136: 755-7.

4 Wilkinson DS. Migrant necrotic erythema revealing a cancer of the pancreas. Ann Dermatol Syphiligr (Paris) 1973; 100: 382-3.

5 Mullans EA, Cohen PR. Iatrogenic necrolytic migratory erythema: a case report and review of nonglucagonoma-associated necrolytic migratory erythema. J Am Acad Dermatol 1998; 38: 866-73.

6 Quirk CM, Seykora J, Wingate BJ, Cotsarelis G. Acrodermatitis enteropathica associated with anorexia nervosa. JAMA 2002; 288: 2655-6.

7 Weismann K, Wadskov S, Mikkelsen HI, Knudsen L, Christensen KC, Storgaard L. Acquired zinc deficiency dermatosis in man. Arch Dermatol 1978; 114: 1509-11.

8 Krasovec M, Frenk E. Acrodermatitis enteropathica secondary to Crohn’s disease. Dermatology 1996; 193: 361-3.

9 Reichel M, Mauro TM, Ziboh VA, Huntley AC, Fletcher MP. Acrodermatitis enteropathica in a patient with the acquired immunodeficiency syndrome. Arch Dermatol 1992; 128: 415-7.

10 Kasper CS, McMurry K. Necrolytic migratory erythema without glucagonoma versus canine superficial necrolytic dermatitis: is hepatic impairment a clue to pathogenesis? J Am Acad Dermatol 1991; 23: 534-41.