Erythema necrolyticum migrans L99.8

Rare dermatological symptoms as partial manifestation of a glucagonoma.

Originally defined as obligatory cutaneous paraneoplasia in glucagonecystic pancreatic tumor(glucagonoma: approx. 80% metastasized at diagnosis) (also known as glucagonoma syndrome). The thesis of "tumor specificity" has been challenged by recent reports after associations with hepatitis B and C, adenocarcinoma, bronchial carcinoma and squamous cell carcinoma have been described.

Thus the erythema necrolyticum migrans is more comprehensively defined as "a polyetiological, monitoring sign of the skin, characterized by a chronic, anular or multi-cellular, scaly, often pustule-bearing or crusty, peripherally progressive erythema".

It is postulated that the increased glucagon leads to a catabolic metabolic state with a deficiency of zinc and various amino acids. This hypothesis is supported by the rapid response of the skin changes to amino acid substitutions. It is remarkable that the clinical and histological picture does not differ from skin changes in zinc deficiency syndrome or biotin deficiency.

Mostly in postmenopausal women.

Centrofacial, periorifcial, inguinal and perianal; rarely trunk and thigh.

Internally: Weight loss, stomatitis, intermittent diarrhea, tendency to thrombosis, diabetic metabolism, hyperglucagonemia, hyperproteinemia, hypokalemia, anemia, glossitis, weight loss.

Dermatologic: Bizarrely configured, centrifugally growing, annular or multibanded, scaly erythema with pustular formation (evidence of Staphylococcus aureus), crusting, and pigmentary shifts.

• Furthermore: angular cheilitis, nail dystrophies.

• Furthermore, signs of pellagra due to nicotinic acid deficiency may occur (van Beek AP et al. 2004).

Note:

• The skin lesions disappear after complete resection of the mostly malignant A-cell islet cell tumor. However, since a large proportion of symptomatic glucagonomas have already metastasized, the success of surgical intervention with regard to dermatological symptoms may not be given.
• In the "non-glucagon-induced" necrolytic erythema, healing of the migratory necrolytic erythema occurs after substitution with amino acids and zinc (Thomaidou E et al. 2016).

Hyperglycemia, SGS elevation. Elevated plasma glucagon levels.

In the acute stage image of a subcorneal pustule with ballooned, necrobiotic and dyskeratotic keratinocytes. Typical is the detection of pale necrobiosis zones (maturation defect) running through the surface epithelium in a street pattern. Confluent parakeratosis with exoserosis and penetrating neutrophilic leukocytes. Superimposed orthokeratosis.

Erythema anulare centrifugum-likepsoriasis: Rare, mild special form of pustular psoriasis generalisata (Zumbusch type) with the formation of characteristic, anular and confluent garland-shaped (circulatory) skin patterns. In erythema anulare centrifugum-like psoriasis (EACP), the general symptoms of pustulosa generalisata psoriasis are absent.

Diseases of the pemphigus group: Detection of pephigus antibodies

Subcorneal pustulosis: Exanthematic chronic clinical picture. Easily bursting pustules are characteristic. No circinar formations.

Acrodermatitis enteropathica: Rare, autosomal recessive inherited disease in which vesiculo-pustular, sometimes also eczematous, pluriorificial (perioral, genitoanal) and acral skin changes as well as diarrhea and alopecia occur due to insufficient absorption of the zinc contained in the normal diet.

Candidiasis: whitish, mostly intertriginous or periorificial pustules. Detection of yeasts in culture.

Zieve syndrome: Occurs with chronic alcohol consumption and consecutive liver insufficiency. In the course of the disease, occurrence of non-itching (almost asymptomatic), scaly, centrifugally growing, circulatory erythema (probably identical to erythema necroticans migrans).

Tumor search and repair!

1. Becker SW, Kahn D, Rothman S (1942) Cutaneous manifestations of internal malignant tumors. Arch Dermatol Syphilol 45: 1069-1080.
2. Bruce H et al (2009) Cutaneous manifestations of internal malignancy. Cancer J Clin 59: 73-98

3. Halvorson SA et al (2013) Putting the pieces together: necrolytic migratory erythema and the glucagonoma syndrome. J Gen Intern Med 28:1525-1529.

4. Leibovici V et al (1987) The glucagonoma syndrome. J Dermatol 14: 491-496.
5. Luber AJ et al (2015) Pediatric Necrolytic Migratory Erythema as a Presenting Sign of Glucagonoma Syndrome. Br J Dermatol doi: 10.1111/bjd.142982:
6. Möhrenschläger M et al (1999) Squamous cell carcinoma-associated necrolytic migratory erythema. Dermatologist 50: 988-202
7. Pfau A et al (1995) The glucagonoma syndrome - clinic and therapy. Z Hautkr 70: 725-728.
8. Pujol RM et al (2004) Necrolytic migratory erythema: clinicopathologic study of 13 cases. Int J Dermatol 43: 12-18
9. Rappersberger K et al (1987) The glucagonoma syndrome. Dermatologist 38: 589-598
10. Thomaidou E et al (2016) Rapid Clearance of Necrolytic Migratory Erythema Following Intravenous Administration of AminoAcids. JAMA Dermatol 152:345-346
11. van Beek AP et al (2004) The glucagonoma syndrome and necrolytic migratory erythema: a clinical review. Eur J Endocrinol 151: 531-537.
12. Vogl A et al (2005) Skin and alcohol. J Dtsch Dermatol Ges 3: 788-790.
13. Zeng J et al (2003) Glucagonoma syndrome: diagnosis and treatment. J Am Acad Dermatol 48: 297-298.