INTERNATIONAL JOURNAL OF LEPROSY^

Volume 68, Number 3Printed in the U.S.A.

(ISSN 0148-916X)

Hansen's Disease in a Patient with aHistory of Sarcoidosisl

Anne E. Burdick, Ali Hendi, George W. Elgart, Lourdes Barquin, andDavid M. Scollard2

Hansen's Disease (HD) and sarcoidosisare both granulomatous disorders which mayhave similar cutaneous presentations. Therehave been several reported cases in the lit-erature of sarcoidosis masquerading as HDand vice-versa (249 11, 15s.) To our knowl-edge, there have been no cases of concomi-tant HD and sarcoidosis. We report here acase of HD developing in a patient with ahistory of sarcoidosis for many years.

CASE REPORTA 50-year-old, white Latin woman pre-

sented to the University of Miami/JacksonMemorial Hospital Hansen's Disease Clinic(HDC), Miami, Florida, U.S.A., with a 13-year history of sarcoidosis and a recent skinbiopsy which showed paucibacillary HD.She was bom in New York City, lived inPuerto Rico from age 17 to 22, and thenlived in the Virgin Islands for 10 years. Atage 27, the patient noted a hypopigmentederuption on her ears and left lower eyelid.No diagnosis or treatment was establishedat that time. At age 31, she received sili-cone-gel breast implants.

At age 37, the patient was diagnosedwith sarcoidosis based on biopsies of thecervical, submental and mediastinal lymphnodes, which revealed noncaseating granu-lomatous lymphadenitis with numerous lip-

' Received for publication on 25 May 1999. Ac-cepted for publication in revised form on 15 June2000.

A. E. Burdick, M.D., M.P.H.; A. Hendi, M.D.; G.W. Elgart, M.D.; L. Barquin, R.N., Department of Der-matology and Cutaneous Surgery, University of MiamiSchool of Medicine, Jackson Memorial Hospital, RO.Box 016250 (R-250), Miami, Florida 33101, U.S.A.D. M. Scollard, M.D., Ph.D., GWL Hansen's DiseaseCenter at Louisiana State University, P.O. Box 25072,Baton Rouge, Louisiana, U.S.A.

Reprint requests to Dr. Burdick at the above ad-dress or FAX 1-305-243-6468; e-mail:aburdick@med.miami.edu

idized cells, and no organisms were identi-fied with special stains. There were no for-eign body giant cells noted. Her angiotensinconverting enzyme (ACE) level was normaland her serum calcium levei was low. Thesedimentation rate was mildly elevated at20 mm/hr (normal: <20 mm/hr for women).The patient was started on prednisone andhydroxychloroquine sulfate. Her symptomsof fatigue and external dyspnea persisteddespite this therapy. At 44 years of age, shehad her silicone-gel breast implants re-moved due to leakage. The same year, achest X-ray revealed prominent hila bilater-ally with possible adenopathy. During thenext 4 years, surgical specimens taken fromthe ethmoids and nasal bone in operationsto treat her chronic sinusitis and skin biop-sies from both hands revealed noncaseatinggranulomatous inflammation with no mi-croorganisms detected on special stains. Noforeign particles were identified.

At age 48, electromyogram studies re-vealed a sensory polyneuropathy of thehands and feet for which she was started ongabapentin. One year later, a violaceous, in-durated plaque on the right cheek was biop-sied by her dermatologist. The specimen,read by the National Ambulatory Hansen'sDisease Program (NAHDP), showed re-placement of approximately 50% of thedemiis by granulomatous inflammatory in-filtrates. The granulomas were well formedwith a peripheral mantle of lymphocytes.There was necrosis and rare acid-fast bacilli(AFB) were identified. The cutaneousnerves were not well represented in thesample. Polymerase chain reaction (PCR)of this specimen was negative for Mycobac-terium leprae. Based on this biopsy, a diag-nosis of tuberculoid HD was made and thepatient was started on dapsone 100 mg andrifampin 600 mg daily, with slight improve-ment of her skin lesions. The patient's sar-coidosis medication was discontinued.

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308^ International Journal of Leprosy^ 2000

FIG. 1. Violaceous, indurated lesions of thecheeks, nose, and forehead with madarosis.

In March 1998, after 4 months of dap-sone and rifampin therapy, the patient pre-sented to the HDC for a second opinion.She presented with four 3-cm to 5-cm vio-laceous, indurated hypoesthetic plaques onthe cheeks, forehead, and nose; madarosis,bilateral enlarged ninar nerves, and a mildright ulnar neuritis (Fig. 1). She also hadfour 2-cm to 3-cm red indurated plaques onthe right arm and one on the left hand. Aliof these lesions had decreased sensation asassessed by the Hand Set Sensory TestingNylon Filamentcarv®, ranging from resid-ual texture sensation to loss of protectivesensation. Biopsy specimens from her rightarm and left hand were sent to the NAHDPand revealed replacement of 70%-80% ofthe dermis by granulomatous infiammatoryinfiltrates with cutaneous nerve involve-ment within some granulomas (Fig. 2).Other granulomas had small foci of coagu-lative necrosis; however, no AFB wereidentified in the Fite-stained sections. Dueto the large number of skin lesions, the di-agnosis was changed to mid-borderline HD,

and she was continued on dapsone and ri-fampin. The patient refused clofazaminedue to the pigmentary changes associatedwith the drug. Five months after beginningmultidrug therapy, the patient developed atype 1 reaction with edema and mildparaesthesias of the facial plaques which re-sponded to ibuprofen 400 mg q.i.d. Threemonths after the initiation of HD medica-tion, the patient agreed to the addition ofclofazamine 50 mg q.d. Although her facialeruption became less violaceous on thistherapy, she continued to develop new fa-cial lesions.

A reticulin stain of the left hand skinbiopsy in September 1998 showed preser-vation of the normal reticulin network (Fig.3). A biopsy of a right nasolabial foldplaque showed noncaseating granuloma-tous dermatitis consistent with sarcoidosis,with no organisms identified on Fite stain-ing. Slit-skin smears of the earlobes, el-bows, and knees were negative for AFB.

A biopsy of a new perioral lesion also re-vealed noncaseating granulomatous inflam-mation with no AFB on Fite staining, con-sistent with sarcoidosis. Slit-lamp examina-tion of the eyes demonstrated clear corneaswith normal maculae and no nodules. Peri-odic ear, nose and throat examinations re-vealed a chronic sinusitis, clear, open anddraining nasal passages with chronic debris,eschar, and friable mucosa. No nasoseptalthinning, ulceration or perforation were ev-ident.

In addition, repeat studies revealed bilat-eral hilar fullness on chest X-ray and an el-evated serum ACE levei of 115 U/L (18-52U/L normal range). It was concluded thatthe patient had concomitant HD and sar-coidosis. Intralesional triamcinolone ace-tonide (5 mg/cc) treatment of her facialplaques resulted in decreased induration ofthese lesions. After 4 months of intrale-sional steroids, prednisone 10 mg daily wasadded with further improvement of the in-duration. The patient has had no progres-sion of her neurosensory loss since mul-tidrug therapy has been instituted.

DISCUSSIONSarcoidosis is a multisystem disease of

unknown etiology. It is characterized bynoncaseating granulomas that may involveany organ. The lungs and thoracic lymph

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68, 3^Burdick, et al.: HD and Sarcoidosis^ 309

FIG. 2. Granulomatous infiammation of the dermis with involvement of cutaneous nerves. A = Extensive re-placement of the dermis by epithelioid granulomas was observed with involvement of cutaneous nerves in sev-eral foci (arrows). B = Closer examination of the nerve indicated by the short arrow in A reveals perineurial andendoneurial infiltration by mononuclear cells, including lymphocytes and vacuolated histiocytes. (A bar = 100um; B bar = 50 um.)

nodes are almost always affected, followedby the skin, eyes, and other organs (6). Thediagnosis of sarcoidosis is one of exclusion.Other causes of granulomatous inflamma-tion (infectious agents, organic and mor-ganhe agents, neoplasia and autoimmunedisorders) need to be ruled out. There areno definitive diagnostic blood, skin, or radi-ographic tests specific for sarcoidosis. Spe-cific skin lesions in sarcoidosis reveal non-caseating granulomas, and include papules,plaques, nodules, and subcutaneous changesin old scars (16). Laboratory findings mayinclude hypercalciuria, with or without hy-percalcemia (6), and elevated serum ACEleveis (16). However, serum ACE is elevatedin only 60% of patients with sarcoidosis (''')and adds little diagnostic value because ofits low specificity (1,6).

Hansen's disease is a chronic granuloma-tons disease with a spectrum of clinicalpresentations caused by M. leprae. Thespectrum of HD ranges from a high cell-mediated response to M. leprae in tubercu-

loid HD to a low cell-mediated response inlepromatous HD. Patients may also presentwith borderline HD in between the polarforms of the disease (9. The typical clini-cal features of HD include well-definederythematous skin lesions and enlarged pe-ripheral nerves with pain and/or sensoryloss. Histopathologic evidence of HD in-eludes granulomatous inflammation, AFB,and involvement of cutaneous nerves withfoci of necrosis. A surrounding lymphocyticinflammation can often be appreciated. En-demic areas of HD include central Africa,Southeast Asia, and Latin America (16).

Sarcoidosis and HD are both granuloma-tous disorders that can have similar clinicaland histopathological features. Althoughsarcoidosis is classically described as hav-ing noncaseating granulomas, the granulo-mas of HD are also usually noncaseating.There have been reported cases of difficultyin distinguishing the two disorders (2'4' 9' "' 15).One case report describes such a diagnosticdilemma in a patient with an erythematous

310^International Journal of Leprosy^ 2000

FIG. 3. Reticulin stain showing. intact reticulinnetwork (x10).

infiltrated facial plaque. Interestingly, thediscussion notes that dermatologists in HD-endemic areas would tend to make the diag-nosis of HD for a patient with sarcoidosis (4).

Our patient was originally diagnosedwith sarcoidosis, and her diagnosis waschanged to HD after a facial plaque biopsyrevealed granulomatous inflammation andrare AFB. After further work-up, it wasconcluded that she has both sarcoidosis andHD, based on the clinical and histopatho-logic findings that were consistent withboth disorders. Reticulin staining and PCRwere used as diagnostic tools.

Reticulin fibers are composed of Type IIIcollagen, which is a normal component ofthe dermis. Reticulin fibers are present ingranulomas and make up a network that canbe seen with special staining (14). In tuber-culoid HD there is "patchy destruction andfragmentation of the reticulin" (7). Hence, itis hypothesized that the preservation of thenormal reticulin network is consistent withsarcoidosis since the network appears to be

disrupted in infectious processes. In our pa-tient there is evidence of sarcoidosis andHD. A biopsy of a plaque on her left handrevealed a preserved reticulin network sug-gestive of sarcoidosis. The same biopsyalso had areas of necrosis within the granu-lomas which might be consistent with HD.

PCR has been used in the detection of M.leprae in biopsy specimens of patients sus-pected of having HD lesions. In endemicregions, high sensitivity and specificityhave been reported in detecting M. leprae(3). However, in a nonendemic population itis recommended to use PCR in cases withAFB present on microscopy who haveatypical histopathologic and clinicai fea-tures which may obscure the diagnosis (13).In our patient, PCR of a facial lesion did notdetect M. leprae.

It has been suggested that silicone maybe responsible for the development of sar-coidosis (17, IS). However, the relationshipbetween silicone and sarcoidosis is a con-troversial issue (8,12) . Our patient has a his-tory of silicone-gel breast implants thatleaked and were subsequently removed.However, the history of ruptured silicone-gel breast implants does not alter the diag-nosis of sarcoidosis because the first skinlesions appeared 4 years prior to the place-ment of the implants. In addition, multiplebiopsies from the lymph nodes and skin didnot reveal foreign-body-type giant cells.

SUMMARYWe report a rare case of concomitant

Hansen's disease (HD) and sarcoidosis.Reticulin staining may be a helpful diag-nostic tool in establishing the diagnosis ofsarcoidosis in skin lesions. The diagnosis ofHD can be established despite negativepolymerase chain reaction results for thedetection of Mycobacterium leprae DNA.Finally, a well-established diagnosis of sar-coidosis does not preclude the developmentof another granulomatous disorder. Hence,when new lesions developed in a patientwith sarcoidosis despite appropriate ther-apy, other concurrent diagnoses should bepursued.

RESUMENReportamos un caso raro de enfermedad de Hansen

(HD) concomitante con sarcoidosis. La tinción de reti-culina puede ser útil para establecer el diagnóstico de

68, 3^Burdick, et al.: HD and Sarcoidosis^311

sarcoidosis en las lesiones de la piei. El diagnóstico deHD puede ser establecido a pesar de los resultadosnegativos de la reacción en cadena de ia polimerasapara la detección de DNA de Mycobacterium leprae.Finalmente, un diagnóstico bien establecido de sar-coidosis no excluye el desarrollo de otro desordengranulomatoso. Por esto, un paciente con sarcoidosisapropiadamente tratado que desarrolle nuevas lesionesdebe estudiarse a fondo para buscar enfermedades con-currentes.

RÉSUMÉNous rapportons ici un cas inhabituel concomitant

de maladie de Hansen (MH) et de sarcoklose. La col-oration des fibres de réticuline parait être un outils di-agnostic utile pour établir le diagnostic de sarcotdose àpartir de lésions cutanées. Le diagnostic de MH peutêtre posé en dépit de résultats négatifs utilisant la tech-nique de polymérase en chaine pour détecter l'ADN deMycobacterium leprae. Finalement, un diagnostic desarcoklose n' écarte pas à priori te développement d'unautre désordre granulomateux. Ainsi, lorsque de nou-velles lésions se développent chez un patient atteint desarco'idose en dépit d'une thérapeutique adéquate, unerecherche en vue d'autres diagnostics devrait êtrepoursuivie.

Acknowledgment. The authors would like to ac-knowledge Tom Gillis, Ph.D., Chief, Molecular Biol-ogy Department, National Hansen's Disease Center atLouisiana State University, Baton Rouge, Louisiana,U.S.A., for performing the polymeráse chain reactionon the tissue specimen.

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