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INTERNA Tional JOURNAL of Leprosy and Other Mycobacterial Diseases INIFR--:" I ION.o\ .. JOI' M:'\AI. 0'- I .F.I'KO.'" Volume :,l6, N umher : ~ ' )1';,,11'(1;11 III.,. U .S.A . INTERNA TIONAl JOURNAL OF lEPROSY And Other Mycobacterial Diseases \'OLUtll E 38, N UMBI·:rt :3 .] lJLy-SI': I'TI':N1 BErt, 1970 Histologic Characteristics of Granuloma Multiforme (Mkar Disease) Including a Comparison with Leprosy and Granuloma Annulare Report of First Case from Congo (Kinshasa) 1 Wayne M. Meyers, Daniel H. Connor and Ralph Shannon!!·3 Granuloma mu)tiformc is a skin disease Clinicall y granuloma multiformc, tuber­ of unknown cause that clinically resembles culoid leprosy, and granuloma annulare tuberculoid leprosy and granuloma annu­ have a number of similarities: (1) the lare. Until now the disease has been repoli­ lesions are usually few; (2) they develop ed only from Nigeria and Kenya. H ere we slowly, and (3 ) plaques expand peripher­ present clinical and histopathologic findin gs ally while theiT centers become hard and in a patient with granuloma l1lultiforme resolve, producing a circinate pattern. His­ from Congo (Kin shasa). topathologically, granuloma annulare and The disease was first described by Leiker granuloma multiforme are similar, but tu­ et a1. (4) in 1964 after a dctailed study of berculoid leprosy has distinctive features. several hundred patients detected in vari­ Histologic characteristics of the three dis. ous leprosaria in the Mkar area of nOlthern eases are listed in Table 1. Nigeria. Subsequently Browne (2) discov­ ered 20 patients with granuloma l1lulti­ REPORT OF A CASE forme among 400 being treated for leprosy A 45 year old Congolese man of the in neighboring eastern Nigeria. More re­ Baluba tribe was examined in May 1967 cently Leiker and Ziedses des Plantes (3) during a survey of 200 patients under treat­ and Verhagen et aZ. (7) have observed ment for leprosy at the Kellersberger Mem­ granuloma multiforme in Kenya. orial Hospital, Bibanga, Kasai Province, Congo. He stated that his deceased father 1 R eceived for publication 28 May 1970. 2 W. M. Meyers, \I.D., Ph.D. , Institll t Medical had had leprosy. He was a lifelong resident Evangelique, Kimpese. Democratic Repllblic of of this area, which is about 60 mil es east of Congo; D. H. Connor, M.D., Geographic Pathology the town of Mbuji Mayi. The region is hilly Di vision , Armed Forces Institute of Pathology, Washington, D.C. 2030.5; R. Shannon. M.D., Kell crs· savannah, with sandy soil, and has distinct berger ;Vl emorial Hospital , Bibanga, Lllluabourg, wet and dry seasons. Democratic R epllblic of Congo. Clinical findings. In 1960 the patient :! Dr. Meyers was a Leonard ' ,Vood Memorial· I'\'ational Institlltes of Hea lth fellow in Research noted pruritic papules where well­ Pa thology in Leprosy at the time this work was d veloped les ions were found on examina­ done. R f'qllesl for r(!f>rints shollid be addressed to Or. tion-left deltoid, right forearm, right lum­ D. H. (;onnor. bar, and sacral areas. These papules had 242 International Jou.rnal of Leprosy 1970 TA BI,E L. Dist£u{Juishill{J characteristics of (Jra'lIuloma muil'IJOl'nle, gralltliol1ta allllulare, and luberculm'd leprosy. Granuloma multiforme Granuloma annulare 'fuberculoid leprosy -------------------_._-------------------_._--_. Clinical A diBease of adults. A disease of children. r\ di:;ease of children and finding;; Upper body u ~ u a ll y tn ­ Us u a ll~ ' hands and feet adults. No itching. Sen­ volved. Le;;ions itch. No in volved, No sensory loss sory los,o; 111 lesions and sensory lo s,.; or nervr en­ or nerve en la rgemen t. frequrnt nerve enla rg('­ largement.. ment , ----------_._----------------------------_._-- Histopathologic Random di,.;tri bution of Foci of coll agen d~'gen e r ­ Granulomas may in volve findings granuloma" tn dermi,.; , at ion ,.; urround('d by a all layers of dermis. No but papillary la.ver gran ul omatous zon('. co llagen degeneration, spa red. Plasma ce ll ,.;, Nerve" in tact. Plasma Nerves damaged, Acid­ mast ce ll s, and eo"in o­ cclb, mast ('e ll s, and fast baeilli pre"ent within phils sometim e~ present. eOsin ophil" som(' times nerves. Nerves in tact. Focal co l­ present. Ly mphocytic in ­ lagen degeneration (3) , as fil trate around \'essels. well as fragmentation and No etiologic agent phagocytosis of ela,.;tica, known. No etiologic agent kn own. ----------------_·------1-----·_---------------------- Re .~ ponse t (> No re"ponse to diamino !\ifa~ ' resolve spontane­ T end to be se lf-healing, therapy diphenyl ," ulfone, Lesions ously or ma.\' I'('spond to but healing hastened b.v per,.; i"t fo r year" and local steroid". DDS. even tuall~ ' heal spon­ taneousl.\·. graduall y progressed to form the present Mitsuda-Hayashi lepromin ) produced an lesions, which ranged from 4 to 8 cm. in area 4 mm. wide after 48 hours (Fernandez greatest diameter and had circinate, ele­ reaction ) and 7 mm. wide after 30 days vated borders ( Figs. 1 and 2). The central ( Mitsuda reaction ). areas were slightly indurated but not ele­ The patient had taken DDS by mouth vated. Most of the lesions were uniformly (300 mgm. twice a week) for 30 months, hypopigmented but two lesions had a few without improvement. areas of hyperpigmentation, 2 to 3 mm. A biopsy specim en was taken from the wide. In none of the lesions was there loss elevated edge of a lesion in the lumbar of sensitivity to light touch nor to discrimi­ region and fix ed in cold 10 per cent nation between heat and cold. No cutane­ formalin. The specimen included a margin ous nerves were palpable and there was no of normal skin. tenderness of nerves. The remainder of the Histopathologic findings. The fix ed bi­ findings on examination \-"ere normal. opsy specimen was blocked in paraffin, cut Skin smears revealed no acid-fast bacilli at 5 microns, and stained by a combined and skin scrapings revealed no fungi. He­ trichrome-Fite-Faraco ( TRIFF ) method moglobin was 13.5 gm.j 100 ml., and the ( 8). Later, additional sections were cut, white blood cell count was 8,300/ cmm., and a vari ety of other stains were made. with a distribution of 71 per cent polymor­ These included hematoxylin-eosin; Fite­ phonuclear neutrophils, 28 per cent lym­ Faraco for acid-fast bacilli; Movat's pen­ phocytes, and 1 per cent eosinophils. tachrome for elastica, mucin, and coll agen; Routine urine and stool examinations and a periodic acid-Schiff; Giemsa; reticulum; chest roentgenogram revealed no abnor­ Brown and Brenn for bacteri a; and Warth­ malities. The intracutaneous injection of 0.1 in-Starry for spirochetes. ml. lepromin (Wade modification of the Granulomas were prominent within the 38, 3 Me!J ers et 01 .: Histologic Characteristics of Granuloma .\1I1.ltiforme 243 Flc . 1. Lcsions of th e left deltoid and right lumbar regions are shown. The lesions have raised serpiginous margins which surround a hroad sli gh tl y indurated and sli ghtly hypopigmcnted central zOlle. ( AFIP neg. 69-3643). Flc. 2. Lesion on the left arm. It has a smooth lo\\'er margin and a seripiginous margin ahovt'. ( AFIP Ilcg. 69-8G-L5). 244 International Journal of Leprosy 1970 dermis. They were most conspicuous at the here described is the first reported from margin of the lesion beneath a slight eleva­ south of the equatorial forest of central tion of the epidermis and were present in Africa. Personal experience (W.M.M.) in­ all layers of the dermis, except for a narrow dicates that granuloma multiforme is "free" zone beneath the basal layer (Fig. 3, uncommon in Congo. No case has yet been top and Fig. 4 ). The granulomas were not found in the lower Congo or North Kivu circumscribed, and merged with surroun­ areas ( in the Ituri fores t ) among patients ding dermal collagen. They were composed bein g treated for leprosy, and our patient of epithelioid cells, histiocytes, and was the only one found among 200 patients Langhans' giant cells and contained a few at a single location in the Kasai Province. plasma cells, mast cell s eosinophilic leu­ Additional surveys are essential ·to deter­ kocytes, and lymphocytes ( Fig. 5). Reticu­ mine the prevalence and distribution of lum and collagen fibers traversed the gran­ granuloma multiforme in Congo. ulomas. No definite evidence of degener­ The cause of granuloma multiforme is ation of collagen fibers was seen. The col­ not known. No mi croorganisms have been lagen fi.bers were not tinctorially altered, seen in the lesions, but cultures for bacteria nor had they lost their normal bire­ and viruses have not been done. An inA am­ fringence. Between the granulomas, and matory or allergic response to insect bites distinct from them, were scaHered collec­ or stings has been suggested ( l . ~ ). Ver­ tions of plasma cells, especially in the loose hagen et al. (7) believe that granuloma connective tissue around the dermal ap­ multiforme may be a variant of granuloma pendages, vessels, and nerves ( Fig. 6 ). annulare, atypical forms of which have Dermal elasti ca was strikingly reduced been described following bites by the gnat within the lesion, and each of the granulo­ Culicoides furan s in the Canal Zone (G) . mas contained minute fragments of phago­ Culicoides sp, are w ide ly distribute d cytosed elastic fibers. Both histiocytes and throughout central Africa, but there is at giant cells contained fragments of elastica present no direct evidence to implicate this ( Fig 3, bottom left and right), and some of or any other insect. the phagocytosed fragments were sur­ Marshall et al. (5) in a detailed study of rounded by acid mucosaccharide.
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