anaemia, necrolytic migratory erythema and markedly raised glucagon levels. Investigations demonstrated a tumour in the tail of the pancreas with metastases ...
Journal of the Royal Society of Medicine Volume 82 September 1989 which may indicate the underlying genus or species3. Yellow granules, as noted in this case, are produced by a number of species, including Actinomyces israelii and Actinomadura madurae. The genus Actinomyces (spp maduraer peUetie) isrep ly responsible for between 10 and 20% ofall mycetomas, more than half of these being due to A. madurae'4. A worldwide study of mycetoma reported 850 cases between 1942 and 19628, though the true incidence is uncertain. Forty-four cases were described in the UK between 1963 and 19814, in two of which the causal organism was identified as being A. madurae. The literature reports less than 10 cases of A. madurae since 1970. Involvement of the foot is described in almost 80% of cases of mycetoma57'9 0, other sites being the thigh and knee (3%), trunk (4%), upper limb (9%) and head and neck (4%). As a soil-borne saprophyte, the infection is thought to follow thorn penetration, with a history of some trauma elicited in 30-60% of cases. We have identified one previous report of A mad urae involving the thigh and knee, descibed in a Sudanese hospital messenger12. Supporting the findings of in vitro sensitivity studies13'14 success has met the use of co-timoaxazolel', streptomycin145 and tetracycline'6 in the ma ent of A. madurae infection. Penicillin is the drug of choice for actinomycosis7, but has always proved ineffective against A. madurac". On this basis, it seems unlikely that penicillin was responsible for the clinical improvement. The prognosis for actinomycetoma is good, with a combination of surgical drainage and the appropriate antibiotic therapy'8"9 achieving a cure in more than 60% of cases, and failing to achieve significant improvement in less than 5%2. The management of fungalmycetoma is less satisfactory as the response to antifngl agent is often poor, and amputation may become the last resort. Acknowledgment. Thanks are due to Professor D W R Mackenzie, Director of the Mycological Reference Laboratory, Colindale and his staff, for their work in identifying A madurae, and Dr Roland Davies for his kind suggestions. References 1 Maghoub ES, Murray IG. Mycetoma London: William Heinemann, 1973 2 Kobayashi GS. Actinomycetes: the fungus-like bacteria. In: Davis BD, ed. Microbiology. Philadelphia: Harper & Row, 1980
The glucagonoma syndrome
M L Price MA MRCP C R Darley MD MRCP N Kirkham MRCPath Brighton General Hospital, Elm Grove, Brighton Keywords: glucagonoma syndrome; eczematous rash
The case is described of a woman who developed typical features ofthe glucagonoma syndrome incluing weight loss, anaemia, necrolytic migratory erythema and markedly raised glucagon levels. Investigations demonstrated a tumour in the tail of the pancreas with metastases in the liver. The typical rash was preceded for two years by a nonspecific eczematous eruption. Case report A 65-year-old Caucasian woman presented to the dermatology department with an eczematous rash on the legs. Some months previously she had complained of severe dyspeptic
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3 Madcinnon SE, Artagaveytia Allende RC. The main species of pathogenic aerobic actinomycetes causing mycetomas. Trans R Soc Trop Hyg Med 1976;50:31-9 4 Hay RJ, Mackenzie DWR. Mycetoma (Maura foot) in the Unitd Kingdom - a survey of forty-four cases. Clin Exp Dermatol 1983,8:553-62 5 Lynch JB. Mycetoma in the Sudan. Ann R CoU Surg Engi
1965;3:319-34 6 Khan KA, Khan AF, Msih M, Farooqui AH, Ansai AM. Clinical and pathological fmdng of mycetoma with special reference to the aetiology. Asian Med J 1984;27:250-7 7 Desai SC, Pardanani DS, Sieedevi N, Mehta RS. Studies in Mycetoma. Clinical, mycological, histological and radiological studies on forty cases of Mycetoma, with a note on its history and epidemiology in India. Indian J Surg 1970;32:427-47 8 Mariat F. Sur la distributioqn geographique et la repartition des agents des mycetomes. BuU Soc Pathol Exot Filiales 1963; 56:34-45 9 Venugopal TV, Venugopal PV, Paramasivan CN, Shetty BMV, Sulramanian S. Mycetomas in Madras. Sabouraudia 1977; :15:17-22 10 Tight RR, Bartlett MS. Actinomycetoma in the United States. Rev Infect Dis 1981;3:1139-50 11 El Mogiraby, IM. Mycetoma in the Gezira. Sudan Med J
1971*.77-89 12 Mahgoub ES. Treatment of actinomycetoma with sulphamethoxazole and trimethoprim. Am J Trop Med Hyg 1972; 21:332-5 13 M nnon JE, Artagaveytia-Allende RC, Garcia-Zarron N. Inhibitory effects of chemotherapeutic agents on the growth of causal organisms of exogenous mycetomas and nocardiosis. Trans R Soc Trop Med Hyg 1958;52:78-86 14 Ziprokowsky L, Altmann G, Dalith F, Spitz U. Mycetoma Pedis -4 cases treated with streptomycin. Arch Dermatol 1957;75.855-63 15 &hewach-millet M, Ziprokowski L, Fenstein A, Cvibah T. Mycetoma pedis: a report of two cases. Isr J Med Sci 1973; 9:900-2 16 Kamalam A, Thambiah AS. Suprabasal bulla in mycetoma. Mykosen 1981;242:43-6 17 Harvey JC, Cantrell JR, Fisher AM. Actinomycosis: its recognition and treatment. Ann Intern Med 1957;46:868-85 18 Desai SC, Pardanani DS, Kher YR et al. Therapeutic investigations in Actinomycetoms. Indian J Surg 1970;32:448-61 19 Sahariah S, Sharma AK, Mittal Vk, Yadav RVS. Mycetoma of lower extremity. J Postgrad Med 1978;24:113-16 20 Mahgoub ES. Medical management of mycetoma. Bull WHO 1976;54:303-10
(Accepted 23 March 1989)
symptoms but a barium meal had failed to show any abnormality. The rash was thought to be varicose in nature and responded partially to topical emollients and steroids. Two years later she began to lose weight and was found to be anaemic (normochromic/normocytic). In addition the rash altered dramatically in appearance and became more extensive with perioral (Figure 1) and perianal involvement. There was an accompanying stomatitis. The eruption was erythematous and exudative with a tendency both to extend and heal rapidly. Some bullae developed particularly on dependent parts (Figure 2). A barium meal now showed a mass displacing the posterior aspect of the stomach and a computed tomography scan confirmed the presence of a carcinoma of the tail of the pancreas with multiple liver metastases. Glucagon levels were over 500 pmol/A (normal: less than 50 pmol1). At no stage did the patient develop evidence of diabetes mellitus. In view ofthe metastases, surgery was not attempted and the patient was treated symptomatically with a high protein diet, zinc supplements and the continued application of topical steroids. The severity of her rash varied considerably throughout the ensuing months, requiring inpatient care on two occasions, when the rash responded well to intensive
Case presented to Section of Dermatology, 19 December 1985
0141-0768/89/ 090553-02/$02.00/0 © 1989 The Royal Society of Medicine
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Journal of the Royal Society of Medicine Volume 82 September 1989
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Figure 1. Perioral and facial eruption
topical treatment. The patient died three years after her. initial referral. A postmortem, was not performed. Histopathology of sections from early skin leions showed a subtle disruption in the upper layers of the stratum malpighii but no frank necrolysis. The overlying-stratum corneum was densely parakeratotic., In older lesiobs the epidermis appeared normal apart from a thick, overlying parakeratotic crust. Discussion
Glucagonoma is an alpha cell tumour ofthe pancreas which synthesizes pancreatic glucagon and occasionally other peptides. Such tumours occur in adulthood, are more common in women and the majority have metastasized at the time of presentation. The most diagnostic clinical feature is a cutaneous rash which has been termed necrotizing migratory
erythema'. The majority of patients develop diabetes mellitus2. In those in whom it does not occur, such as the case presented, there is thought to be either coexistent insulin production by a mixed tumour or compensatory hyper-insulinism. Other clinical features include a normochrom*icnormocytic anaemia, weight loss, angular statis, glossitis, diarrhoea and venous thrombosis. Surgical excision of the uncommon single resectable tumour results mi dramatic clinical improvement, including prompt disappearance of the rash34. In patients with non-respectable primary tumours or metastases, s which is cytotoxic to pancreatic endocrine cells, often r tumour size and improves symptoms5, while the use of long acting synthetic somatostatin may provide palliation by reducidn glucagon secretion6. Unfortunately both these treatments impaPr insulin secretion and produce diabetes.
PNgure 2 "Notte the bullae and involvement of the karge toe The rash has some similarities to acrodermatitis enteropathica a,nd oral zinc as well as amino acid supplements are beneficial to the skin., On occasion oral tetracycline, corticosteroids and azothiaprine have also been shown to improve the rash. The particular features we wish to stress in thiacase are the non-specific nature of the prodromal rash, the variability and severity of the necrolytic migratory erythema once it developed and the absence of diabetes mellitus. References 1 Willinson DS. Necrolytic migratory erythema with carcinoma of the pancreas. Trans St John's Hosp Dermatol Soc 1973*.44-50 2 MaUinson CN, Bloom SR, Warin AP, et aL A glucagonoma syndrome Z.ancet 1974;ii:1-5 3 Sweet RD. A dermatosis specifically associated with a tumour of pancreatic alpha cells. Br J Dermatol 1974;90:301-8 4 Vandersteen PR, Scheithauer BW. Glucagonoma syndrome, a *clinicopathobic, mmunotche l and ltrurutural study. J Am Acad Dermatol 1985;12:1032-9 -5 Danforth IDN, Triche T, Dop JL, et aL Elevated plasma pTpgluqagQn-lke component with a glucagon secreting tumor. r
N, Eagl Med 1976;295:242-5 Log RO, Adrian TE, Brown MR, et aL Suppressioof panreatic endocrine tumour secretion by long-acting somatostatin analogue. Lancet 1979;ii:764-7
(Accepted 9 December 1988)
