INTERNATIONAL JOURNAL OF LEPROSY Volume 73, Number 3 ...ila.ilsl.br/pdfs/v73n3a02.pdf · vasculitis...

1 Received for publication on May 9, 2005. Accepted for publication on Aug 27, 20052 T. H. Rea, M.D., Emeritus Professor, Division of Dermatology, Keck School of Medicine, University of

Southern California, and Attending Physician, Los Angeles County/University of Southern California MedicalCenter, Los Angeles, California. R. S. Jerskey, LOTR, Prevention of Impairment and Disability Consultant,National Hansen’s Disease Program.

Correspondence and reprint requests to Dr. T. H. Rea, M.D., Division of Dermatology, Keck School ofMedicine, University of Southern California, and Attending Physician, Los Angeles County/University ofSouthern California Medical Center, Los Angeles, California. Division of Dermatology, Room 8440, LAC/USCMedical Center, 1200 N. State St., Los Angeles, CA 90033, USA. e-mail: [email protected].

INTERNATIONAL JOURNAL OF LEPROSY Volume 73, Number 3Printed in the U.S.A.

(ISSN 0148-916X)

INTERNATIONAL JOURNAL OF LEPROSY

and Other Mycobacterial Diseases

VOLUME 73, NUMBER 3 SEPTEMBER 2005

Clinical and Histologic Variations Among

Thirty Patients with Lucio’s Phenomenon and

Pure and Primitive Diffuse Lepromatosis

(Latapi’s Lepromatosis)1

Thomas H. Rea and Robert S. Jerskey2

ABSTRACTThe clinical and histologic experience with 30 patients who had Lucio’s phenomenon,

and pure and primitive diffuse lepromatosis (Latapi’s lepromatosis) has been reviewed. Theunanticipated clinical findings were a male to female ratio of nearly 1:1, a 21 month mediantime of onset of erythema nodosum leprosum (Type 2 reaction) after starting antibacterialtreatment, and an absence of a stocking-glove pattern of anesthesia in 7 patients. The onlyunanticipated histologic finding was a lepromatous-granulomatous vasculitis, occurring incomparatively large vessels, or in vessels made large by pathologic changes, located near thedermal-subcutaneous interface. This finding was present in 6 of the 22 patients with histo-logic material available for review. In 2 of these 6 this vasculitis was identified before theonset of Lucio’s phenomenon. With one conspicuous exception, the onset of treatment witha microbicidal agent was associated with a cessation of new lesions of Lucio’s phenomenonwithin one week. Long-term morbidity, other than Type 2 reaction, was found in 22 of the25 patients followed for more than 1.3 years. Usually this was the consequence of Latapi’slepromatosis, specifically venous insufficiency and/or loss of protective sensation, and onlyrarely from Lucio’s phenomenon, specifically scar formation. Briefly summarized are theseven patients who had had a skin biopsy before the onset of Lucio’s phenomenon, as wellas the two patients who were considered to be atypical. Criteria for the diagnosis of Latapi’slepromatosis, in the absence of Lucio’s phenomenon, are also considered.

RÉSUMÉCet article s’est attaché à faire la revue de l’expérience clinique et histopathologique de

30 patients atteints de phénomène de Lucio et/ou de lèpre lépromateuse pure et primitive-

169

170 International Journal of Leprosy 2005

ment diffuse, encore appelée lèpre lépromateuse de Latapi. Les données cliniques sur-prenantes furent un ratio homme-femme de presque 1:1, un temps médian de 21 mois entrela mise en ouvre d’un traitement antibactérien et le déclanchement d’un érythème noueuxlépreux (réaction de type 2), et l’absence d’une anesthésie distribuée en bas-résille chez 7patients. La lésion histologique non anticipée a été la découverte d’une vasculite léproma-teuse et granulomateuse atteignant des vaisseaux de diamètre relativement élevé ou bien desvaisseaux élargis par les changements histopathologiques, situés prés de l’interfacederme/hypoderme. Cette lésion était présente chez 6 des 22 patients qui présentaient dumatériel histologique pour une revue. Chez 2 de ces 6 individus, cette vasculite fut identifiéeavant le déclenchement du phénomène de Lucio. Lors de phénomène de Lucio et à l’excep-tion d’un cas plutôt remarquable, l’apparition de nouvelles lésions a été interrompue dans lasemaine qui a suivi la mise en place d’un traitement avec un agent bactéricide. Une morbid-ité à long terme, autre que les réactions de type 2, fut trouvée chez 22 des 25 patients qui ontété suivis pendant plus de 1,3 ans. Le plus souvent, cette morbidité était la conséquence dela lèpre lépromateuse de Latapi, spécifiquement l’insuffisance veineuse et/ou la perte de sen-sibilité protectrice, et seulement rarement les conséquence du phénomène de Lucio, spéci-fiquement l’apparition de cicatrices. Brièvement résumés sont les 7 patients qui ont eu unebiopsie cutanée avant l’apparition d’un phénomène de Lucio, ainsi que les 2 patients quifurent considérés comme atypiques. Les critères pour le diagnostic de lèpre lépromateuse deLatapi, en l’absence de phénomène de Lucio, sont également présentés.

RESUMENSe hizo una revisión de los datos clínicos e histológicos de 30 pacientes que habían tenido

el fenómeno de Lucio y lepromatosis difusa pura y primitiva (lepromatosis de Lucio). Loshallazgos clínicos no anticipados fueron: una relación masculino: femenino casi de 1:1, untiempo promedio de aparición de eritema nodoso leproso (reacción de tipo 2) de 21 mesesdespués del inicio del tratamiento antibacteriano, y ausencia del patrón de anestesia “media-guante” (stocking-glove) en 7 pacientes. El único hallazgo histológico no anticipado fue unavasculitis lepromatosa-granulomatosa, presente en vasos comparativamente grandes o envasos agrandados por los cambios patológicos, localizados cerca de la interfase dermo-subcutánea. Este hallazgo estuvo presente en 6 de 22 pacientes con material accesible pararevisión. En 2 de estos 6 pacientes la vasculitis fue identificada antes de la aparición delfenómeno de Lucio. Con una sola excepción, el tratamiento con un agente microbicida es-tuvo asociado con la suspensión, en la primera semana, de nuevas lesiones del fenómeno deLucio. La morbilidad crónica, diferente a la reacción de tipo 2, se encontró en 22 de 25 pa-cientes seguidos por más de 1.3 años.

Usualmente la insuficiencia venosa y/o la pérdida de sensación protectora fueron conse-cuencia de la lepromatosis de Lucio y sólo raramente del fenómeno de Lucio en cuyo casola consecuencia más frecuente fue la formación de cicatriz.

Se describen brevemente los casos de los 7 pacientes que habían tenido una biopsia depiel antes de la aparición del fenómeno de Lucio, y de dos pacientes considerados comoatípicos. También se discuten los criterios para el diagnóstico de la lepromatosis de Latapien ausencia de fenómeno de Lucio.

Since reporting 10 patients with Lucio’sphenomenon (25), seen in this institutionfrom 1969 through 1977, a further 20 hadbeen observed by the end of 2004. Theprimary purpose of this report is to describethe kinds and the extent of the clinical andhistologic findings in all these 30 patientswith Lucio’s phenomenon as well as in theunderlying diffuse lepromatosis. In addi-tion, this report presents data on long-termfollow-up, and details information concern-ing patients who had had a skin biopsyprior to the onset of Lucio’s phenomenon.

Also, a higher incidence of a lepromatous-granulomatous vasculitis (L-GV) wasfound in patients with Lucio’s phenomenonthan was present in those with erythema no-dosum leprosum (Type 2 reaction) or non-reactional lepromatous leprosy.

Concerning history and nomenclature, in1852 Lucio and Alvarado (16) reported anecrotic skin reaction that occurred in lep-rosy, as judged by the concomitant changesof peripheral neuropathy, eyebrow loss, andnasal involvement. These authors also de-scribed the absence of the nodular, dermal

73, 3 Rea and Jerskey: Lucio’s Phenomenon and Latapi’s Lepromatosis 171

lesions expected in leprosy, as well as theassociated fatal termination. Latapi andZamora (15) established that the necrosiswas a result of vascular involvement, andthat the absence of dermal nodules was apart of a diffuse lepromatous infiltrate,which they described in considerable detail.Also, they reported a much better prognosiswith dapsone therapy. Latapi and Zamoracalled the necrotic skin reaction “Lucio’sphenomenon” or “erythema necroticans”and the diffuse, non-nodular lepromatousinfiltration “pure and primitive diffuse lep-romatosis.” For the latter expression, thesynonym “Latapi’s lepromatosis” is pro-posed, and will be used hereafter herein.This gives an appropriate and briefeponymic recognition of Latapi’s importantcontributions. Also, having “Lucio” in twoclosely related eponymic terms, i.e., “Lucioleprosy” and “Lucio’s phenomenon,” oftenis a needless source of confusion.

The initial report of Lucio and Alvaradowas virtually forgotten in 50 years (15). Inthe over 50 years following the report ofLatapi and Zamora (15), both Lucio’s phe-nomenon and the underlying Latapi’s lepro-matosis have been recognized in diverseethnic groups, and in a wide geographicdistribution, including, but not limited to,Louisiana (8), Hawaii (3), Brazil (1, 9, 31),Greece (11), the Near East (30), India (29),Singapore (2), Indonesia (13), and Polynesia(6). Apparently the condition remains rareexcept in Mexicans, Costa Ricans (28), andCubans (18), where its incidence is aptly de-scribed as “not common.”

This retrospective study is somewhat in-complete because of the institutional policyof “deep” storage of charts, and the North-ridge earthquake of January 1994 trashedthe room holding both histologic glassslides and paraffin blocks. The materialavailable was considered sufficient to illus-trate a range of clinical and histologic find-ings, the responses to treatment, and thelong-term morbidity encountered.

MATERIALS AND METHODSThe subjects were patients in the

Hansen’s Disease Clinic or the Dermatol-ogy Clinic of the Los Angeles County-University of Southern California MedicalCenter. Included in this study were all pa-tients who had one or more characteristic

lesions of Lucio’s phenomenon, i.e., ser-rated hemorrhagic infarcts usually arisingin crops, and at least one characteristic signof Latapi’s lepromatosis (see below) or oflepromatous leprosy, but no lepromatousnodules. The diagnosis of Latapi’s lepro-matosis was made after the fact of Lucio’sphenomenon. No criteria for exclusionwere established.

The data base for the clinical informationin this study was compiled from fivesources: the available charts, data ab-stracted from charts for previous publica-tions, clinical photographs obtained beforestarting treatment, patients currently beingfollowed in clinic, and available histologicspecimens. The summary of the histologicchanges was compiled from the materialavailable for review.

RESULTSThe results will be presented in two ways.

First will be 9 brief case reports. Followingthe case reports, the available data on all pa-tients will be summarized in narrative form.

CASE REPORTSThe initial 7 case reports concern those

patients who had had skin biopsies takenprior to the development of Lucio’s phe-nomenon. Five of these biopsy specimenshad been seen by one of us (THR), and 3 ofthese 5 were available for review. Amongthese 7 patients, 4 had a diagnosis of lep-rosy established and treatment initiated be-fore the onset of Lucio’s phenomenon(Cases 2, 3, 6, and 7), whereas 3 had had abiopsy but the diagnosis of leprosy was notmade until the onset of Lucio’s phenome-non (Cases 1, 4, and 5). The remaining 2case reports (Cases 8 and 9) concern thosewho were considered to be atypical.

Patients with skin biopsies prior toLucio’s phenomenon

Case 1. An 18 year old woman soughtcare because of numbness of the hands andfeet of several months duration. Neurol-ogists interpreted her findings to be a pe-ripheral neuropathy secondary to a systemicdisease. Consultation with many medicalspecialties could identify no systemic ill-ness. After 18 months, a skin biopsy takenfrom an area of diminished sensory percep-tion, but otherwise clinically normal skin,

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was interpreted as “normal skin.” Threeyears after her initial presentation crops ofinfarcts of Lucio’s phenomenon quickly ledto the correct diagnosis. A Fite stain thendone on the “normal skin” material demon-strated acid-fast bacilli (AFB) and globiwithin nerves and endothelial cells (slidenot available for review).

Comment: this case illustrates the diffi-culty of making a diagnosis of leprosy inthe absence of a sign more readily associ-ated with leprosy.

Case 2. A 22 year old woman presentedto the obstetrical service in labor with anincidental complaint of eyebrow alopecia,progressing from medial to lateral, of 2 months duration. Because rhinitis wasalso present, leprosy was considered. Abiopsy of clinically normal skin showedAFB and globi in some endothelial cellsand perivascular macrophages (slide notavailable for review). No AFB were foundin placental endothelium. One month afterinitiating dapsone monotherapy, erythemanodosum leprosum (ENL) developed,which was managed with thalidomide.Eight months later the patient was lost tofollow-up, only to return after a 13 monthsabsence with the necrotic lesions of Lucio’sphenomenon and ulcers (biopsy not avail-able for review).

Comment: This case confirms the possi-bility of considering a diagnosis of Latapi’slepromatosis without the infarcts of Lucio’sphenomenon, as suggested by others (9).Also, this is the only patient seen in this se-ries who had ENL prior to having Lucio’sphenomenon. Because of the absence ofAFB in placental endothelial cells, but theirabundance in cutaneous endothelium, thepredilection of AFB for endothelial cells islikely to be organ specific.

Case 3. A 45 year old woman presentedwith eyebrow alopecia, rhinitis, and palpa-ble but not visible, indurated lesions in thesubcutis. Skin biopsy showed, in addition toan extensive lepromatous infiltrate, an AFB-positive, lepromatous-granulomatous vas-culitis (L-GV) in the subcutis, characterizedby endothelial proliferation, macrophagesdissecting between the smooth muscle cellsof the media, and macrophages infiltratingthe adventitia (Fig. 1a, b). Also present wasan aneurysmal lepromatous-granulomatousout-pouching originating in a subcuticular

vessel (Fig. 1c), as well as signs of new ves-sel formation. Our working diagnoses werelepromatous leprosy and a reactional stateof unknown type. She was treated withdaily dapsone and rifampin, as well as pred-nisone and thalidomide. The unknown reac-tional state was managed with decreasingdoses of thalidomide and prednisone, thelatter being discontinued after 5 months.Seven months after initiating treatment, and2 months after stopping prednisone, but stilltaking thalidomide 100 mg daily, the pa-tient developed Lucio’s phenomenon (Fig.1d). Her new Lucio infarcts ceased within 2weeks upon resuming prednisone at 40 mgdaily; the dose being tapered slowly overthe ensuing 5 months.

Comment: This patient made us aware ofinvolvement in larger vessels, or vesselsmade large by pathologic changes, than pre-viously recognized by us. Also, the previ-ous suggestion that viable bacilli might be asine qua non for Lucio’s phenomenon (25)appeared to be incorrect. In retrospect, whatwas called a reactional state of unknowntype was perhaps the L-GV.

Case 4. A 37 year old woman sought carebecause of what was described in her chartas nodular lesions on the arms and legs sug-gestive of erythema nodosum. The report ofa skin biopsy at that time noted inflamma-tion and was interpreted as suggesting ery-thema nodosum. The patient was treatedwith a saturated solution of potassium io-dide. When seen 2 years later for anotherproblem, it was noted that the erythema no-dosum had resolved. After an additional 2years, crops of Lucio’s infarcts developed.Of the 2 biopsy specimens obtained at thistime, both showed characteristic changes ofthe Lucio’s phenomenon, and the onewhich was available for review also demon-strated subcutaneous vessels with endothe-lial proliferation and lumen occlusion (Fig.2a). Also, the biopsy taken four years be-fore the onset of Lucio’s phenomenon wasavailable for review, showing a focal lobu-lar panniculitis consisting of macrophagesand, in the dermis, an arcuate, perivascularinfiltrate of lymphocytes and foamy macro-phages (Virchow cells) (Fig. 2b, c). The lat-ter was interpretable as evidence of a lepro-matous change. The tissue blocks were notavailable.

Comment: Two explanations for the sug-

FIG. 1. From Case 3. a) A low power view of a biopsy from a palpable, but not visible, subcutaneous lesion,on the right arm, which shows in the lower right corner an enlarged vessel in the subcutis with a conspicuous in-ternal elastic lamina. The lumen is occluded, and adventitial involvement is apparent. Heavy infiltration of thedermis is evident. 1.25× objective. b) A high power view of the same vessel as shown in “a.” The now less con-spicuous internal elastic lamina is indicated by wide arrows, but is readily seen in color. The lumen is occluded



gested “erythema nodosum” appear possi-ble. A leprologic hypothesis is the develop-ment of mild, neutrophil-free, transientENL in a patient who had yet to expressother clinical manifestations of leprosy. Analternative explanation is that of a leprosy-unrelated inflammatory disorder occurringon a lepromatous background.

Case 5. A 28 year old man sought carebecause of the development of palpable, butnot visible, nodules in the subcutaneous tis-sue of his legs. The clinical impression wasa vasculitis. A skin biopsy was interpretedas “nodular vasculitis,” the pattern consistingof endothelial proliferation with occlusionof the lumen, as well as a dense infiltrate ofmacrophages in the adventitia (Fig. 3a). Hewas begun on an anti-inflammatory regi-men, which included methotrexate andprednisolone. Five months later he devel-oped an acute, febrile illness, diagnosed asa Salmonella non-typhoid bacteremia, sec-ondary to the ingestion of snake powders.He responded well to intravenousciprofloxacin, and was discharged onciprofloxacin 500 mg twice daily orally,methotrexate 5 mg twice daily, and pred-nisone 80 mg every other day in the morn-ing. One day after discharge he abruptly de-veloped extensive and widely distributedinfarcts of Lucio’s phenomenon. These in-volved about one-third of his body surfacearea, most extensive on the legs (Fig. 3b),and arms, but present also on his ears, face(Fig. 3c), trunk, scrotum, and the urethralmeatus. This patient was promptly readmit-ted, and 1 day later his right hand was af-fected by apparently complete arterial oc-clusion. Circulation was restored by promptintervention, but deep necrosis eventuallyresulted in the loss of the 5th right distalmetacarpal head and the right 5th finger.His left patella was also lost, as a conse-quence of extensive tissue necrosis over theleft knee. A Fite stain on the tissue initiallyinterpreted as “nodular vasculitis” was pos-

itive for AFB in endothelial cells and ad-ventitial macrophages.

Comment: This one patient recapitulatesthree prior case reports. 1) Leprosy maymimic nodular vasculitis (34). 2) Occlusionof large muscular arteries may occur in as-sociation with Lucio’s phenomenon (8). 3)Lucio’s phenomenon may occur in a settingof convalescence from serious infection,i.e., in 2 cases of erysipelas managed withpenicillin (1). (These 2 patients, and Case 5,received antibiotics ineffective against M.leprae.) New infarcts ceased when rifampinwas begun. This patient was the only onewhose prognosis was poor when first seen.

Case 6. A 37 year old woman presentedto another clinic because of eyebrow alope-cia and rhinitis. A skin biopsy confirmed theimpression of lepromatous leprosy (slidenot available for review). She took 100 mgof dapsone daily for 18 years. At age 68, 13years after stopping dapsone, she presentedto this clinic with Lucio’s phenomenon, oc-curring intermittently for one month.

Case 7. A 15 year old boy presented to adermatology clinic in Mexico City becauseof eruptive telangiectasias and eyebrowalopecia. A skin biopsy (not available forreview) established a diagnosis of leprosy.Dapsone treatment was initiated at that timebut he took it infrequently. At age 21 hepresented to our clinic because of leg ulcersand skin infarcts of 6 months duration;telangiectasias were prominent at that time.Dapsone was resumed, but he was seen in-frequently. At age 35 he made 2 visits to ourclinic because of leg ulcers. Two skin biop-sies performed at that time were negativefor AFB (not available for review).

The atypical patientsCase 8. This 45 year old woman satisfied

entry criteria for this study on clinicalgrounds because she had one 8 mm charac-teristic infarct, a perforated nasal septum,total alopecia of eye lashes and eye lids,

←by endothelial proliferation. The lepromatous infiltrate is dissecting between smooth muscle bundles, shown bythin arrows, and is infiltrating the adventitia. 20× objective. c) Elsewhere in the same specimen an aneurysmalchange in a vessel is shown by the relatively dark internal elastic lamina. 10× objective. d) A high power view ofa re-epithelized Lucio’s phenomenon lesion which shows, from outside inward, the old stratum corneum, the nowshrunken infarcted epidermis with a hint of cellular ghosts and persistent melanin, a very thin new stratumcorneum, and new granular cell, prickle cell and basal cell layers. The dermal repair is not complete. Five oc-cluded or congested small vessels are evident. 40× objective. (Images available in color in the electronic edition,www.leprosy-ila.org)

FIG. 2. From Case 4. a) From a Lucio’s phenomenon lesion, a vessel in the subcutis with prominent en-dothelial proliferation, and adventitial infiltration. 40× objective. b) A low power view of an earlier biopsy ob-tained from a red dermal nodule 4 years before the onset of Lucio’s phenomenon, showing epidermal thickening,a superficial infiltrate in the upper dermis, and an arcuate infiltrate in the mid dermis. 10× objective. c) An oil-immersion view from the arcuate infiltrate showing 2 nucleated Virchow cells and the cytoplasm of a 3rd.Lymphocytes are evident, but no neutrophils were found. 90× objective.


several stellate scars, and 3 large leg ulcers,each approximately 10 cm in diameter.Biopsy showed a heavy infiltrate of macro-phages, AFB and globi in some endothelialcells, but no endothelial proliferation. Sheis considered to be atypical because of a“peau d’orange” appearance to the skin ofher forehead and cheeks, as well as beadingon corneal nerves (15). Also, she is the onlypatient in this series with just one infarct,and one of two without endothelialproliferation.

Comment: At present it is unknown ifany of these atypical findings, or a combi-nation thereof, would constitute valid crite-ria for exclusion.

Case 9. A 24 year old man presented tothis clinic with typical Lucio’s phenome-non, and giving a history of similar clinicalfindings, as well as intermittent dapsone usefor 4 years. A lesional biopsy did not showepidermal necrosis (probably exfoliatedduring processing), or congestion of super-ficial vessels, or extravasation of erythro-cytes , but did demonstrate AFB in prolifer-ating as well as in non-proliferating en-dothelial cells, globi in endothelial cells,and passive congestion of deep dermal ves-sels. Also present were larger vessels withlumens occluded from endothelial prolifer-ation, and macrophage infiltration of the ad-ventitia, but no infiltration of the media(Fig. 4a). New lesions ceased to form 4weeks after starting dapsone monotherapy.To this point, on balance, the patient wasconsidered to be typical. Eight years later,in the setting of seemingly good compli-ance with dapsone monotherapy, new Lu-cio’s phenomenon-like infarcts developedon the trunk and extremities. With theworking diagnosis of a relapsing Lucio’sphenomenon, and an inference of dapsoneresistance, dapsone was discontinued, beingreplaced by daily rifampin and dailyminocycline, and the new lesions ceased af-ter 8 weeks. Biopsy now showed epidermalnecrosis, passive congestion of superficialvessels, and endothelial proliferation indeep dermal vessels, but stains for AFBwere repeatedly negative (slides not avail-able for review).

Comment: No support for dapsone resis-tance was found. A self-limited process ofunknown type, unrelated to leprosy, butmimicking Lucio’s phenomenon must beconsidered.

SUMMARY OF ALL CASES

Demographic dataSixteen men and 14 women satisfied in-

clusion criteria. Twenty-five were born inMexico, 2 in Cuba and 3 in the UnitedStates, each of the latter 3 also havingresided in known leprosy-endemic areas ofMexico for more than 5 years. Age at thetime of diagnosis of Lucio phenomenon,leprosy was known in 29 and ranged in du-ration from 15 to 71 years, with a median of34 and an average of 33.7 years.

First sign or symptom of leprosy, andtime to diagnosis

The first sign or symptom attributed toleprosy was alopecia in 16 (eyebrows in 15,extremities in 1), leg ulcers in 4, sensoryimpairment in the hands and/or feet in 3,nasal symptoms in 2 (1 with nose bleeds, 1with congestion), eruptive telangiectasias in2, and infarcts of Lucio’s phenomenon in 2,but was not recorded in 1. The elapsed timefrom the initial sign or symptom to the di-agnosis of leprosy ranged from a minimumof 2 months to a maximum of 10 years,with a median of 3 years and an average of4.1 years.

Mode of presentationOf the 28 patients presenting to our clinic

with Lucio’s phenomenon, the presentingcomplaint was leg ulcers in 14 (duration 2months to 7 years, median 8 months and av-erage 19.7 months). The other 14 com-plained of the infarcts of Lucio’s phenome-non, usually occurring in intermittent crops(duration 5 days to 10 years, median 4months, and average 4.1 months). Both in-farcts and ulcers were characteristicallypresent at presentation, excepting Case 5,who had no ulcers at presentation. The in-farcts were hemorrhagic, slightly indurated,not tender, but sometimes painful. Sharplymarginated, irregularly serrated borderswere characteristic, such that an observerviewing the infarct, whether large or small,from “normal” skin would see a concavity(Fig. 3b, c). Early, pre-hemorrhagic lesionswere seen in only one patient, being slightlyindurated, light blue in color, and having anerythematous halo. (Previously publishedphotomicrographs of this specimen are figs.4 and 5 in Rea and Levan (25), and figs. 3and 4 in Quismorio, et al. (23)) The least


number of infarcts recorded was one, inCase 8. In all other patients the lesions weremultiple, arising in crops, most commonlyon the legs, but less frequently on the thighsand forearms. In one patient, Case 5, the in-farcts were numerous (over 100), widelydistributed, and clearly placed his life inperil. In another patient, 24 infarcts werecounted. And in yet another patient the in-farcts were small, and present only belowthe ankles. Infarcts on the arms resolvedrapidly, behaving more like erosions thanulcers. In 2 patients the infarcts becamebullous. Infarctions in organs other than theskin were not evident.

Ulcers were common on the legs, but oc-casionally on the thighs. Ulcers of recentonset appeared to be the direct sequelae ofthe infarcts, being ovoid and irregular inshape, not exceeding 5 cm in greatest diam-eter. If of long standing, ulcers were roundin shape and up to 10 cm in diameter, per-haps being complicated by neglect and un-suitable topical therapy.

In two patients the onset of Lucio’s phe-nomenon was associated with pregnancy,each ending with a normal delivery. In Case5, the onset occurred while the patient wasconvalescing from a Salmonella bac-teremia. No other potentially precipitatingevents could be identified.

Signs of Latapi’s lepromatosis at thetime of presentation

Absent nodules. The absence of leproma-tous dermal nodules was noted in all 30 pa-tients, with the possible exception of Case8, who had a “peau d’ orange” prominenceto the follicular orifices on the face, pre-sumably the result of infiltration or edema,but no dermal nodules in the conventionalsense.

Diffuse infiltration. Signs of diffuse cuta-neous infiltration were not mentioned aseither present or absent in 8 patients. One ormore signs of diffuse infiltration wererecorded as present in 22 patients. Widen-ing of the nasal root was described in 9 (orretrievable from clinical photographs).Diffuse infiltration in the hands was notedin 9 patients, being variously described as“swelling,” or “non-pitting edema,” of thebacks of the hands, in association with“fusiform fingers.” Changes in the cheeksof the face were variously described in 4 as“red plaques, poorly marginated,” “in-

durated erythema,” or “a cyanotic edema.”“Full” or “swollen” ear lobes were stated to be present in 7 patients. A “duskyswelling” of the feet was described in 1.(Swollen ear lobes and fusiform fingers aresigns of diffuse infiltration not uncom-monly found in patients with ordinary lep-romatous leprosy.)

Subcutaneous plaques. Not visible, non-tender, subcutaneous plaques were foundon the arms or legs in 8 patients, but werenot mentioned as absent in any of the 20other charts available for review.

Telangiectasias. Telangiectasias were de-scribed as eruptive in 3 patients; these per-sisted in 2, but treatment-associated remis-sion occurred in 1. Persistent telangiectaticmats, occurring on the face or upper chest,were noted as present in 7, (masqueradingas spider angiomas, but having no centralarteriole, and upon expression, filling fromthe periphery).

Ordinary changes of lepromatousleprosy at time of presentation

Alopecia. Alopecia of the eyebrows wasstated to be complete in 20, partial in 7, andwas not noted as present or absent in 3.Rhinitis. Rhinitis was stated to be present in25, and was not mentioned as present or ab-sent in 5. Of the 25 with recognized rhinitis,the nasal septum was recorded as perforatedin 9, as intact in 8, but was not mentioned asperforated or intact in 8. Stocking-glove pat-tern sensory impairment (S-GPSI). S-GPSIis a withering away of the sensations medi-ated by the type C sensory fibers, beginningdistally and proceeding proximally. S-GPSIwas recorded as present to some degree in20, as absent in 7, not mentioned as presentor absent in 3. Motor impairment. Motorimpairment was present in only three: twopatients with ulnar nerve involvement andone with common peroneal nerve involve-ment. The motor changes were dispropor-tionately few compared with the magnitudeof the sensory loss.

Routine laboratory findings at presentation

A mild anemia, normochromic and nor-mocytic, was common. The average leuko-cyte count (normal range 3.7–11.6 ×1000/mm3) was 6.5 and the median was6.3, among the 23 initial counts availablefor review. The highest count, 11.9, was


FIG. 3. From Case 5. a) In the center of the field is the largest of several vessels showing endothelial prolif-eration in the specimen from a palpable, but not visible, subcutaneous lesion obtained from the left thigh, 5months before the onset of Lucio’s phenomenon. 20× objective. b) Several lesions of various sizes on the face.Most show the characteristic serrated margins. c) The left knee with adjoining thigh and leg. The skin of the an-terior portion is largely necrotic, but the serrations still evident, although farther apart than in “4b.” Smaller le-sions are evident posteriorly.


seen was in Case 5; the lowest was 3.1. Twocounts were above and 2 were below thenormal limits. Among 19 patients thecardiolipin-based serologic test for syphiliswas reactive or weakly reactive in 15 in 3;of the 15 who were reactive, a Treponema-specific test was positive in 3. Hyperglobu-linemia was common; in 18 patients themean value was 4.8 gm/dl (normal3.0–4.0), the median 5, the high 6.0 and thelow 3.2. Serum albumin values were nor-mal in 7, ranging from 3.8 to 4.6 gm/dl,clearly low in 3, ranging from 2.9 to 3.1,and extreme in 1, being 1.8 in the one pa-tient with extensive infarcts, Case 5.

Response to treatmentCessation of new infarcts. Of the 28 pa-

tients who presented to the clinic with Lu-cio’s phenomenon, 19 were begun on dap-sone alone. Ten of these 19 had no new in-farcts after one week of follow-up. Theremaining 9 continued to develop new in-farcts for up to 5 months after starting treat-ment, 2 of which appeared to worsen beforethey improved. In one of the latter, new le-sions ceased at 6 weeks, in association withthe addition of daily rifampin.

Of the 7 previously untreated patientswith Lucio’s phenomenon who were startedon a daily microbicidal agent (5 with ri-fampin, 1 with clarithromycin and 1 withminocycline) no new infarcts were seen af-ter 7 days. (In these 7, a second daily agentwas added within 2 weeks, so that all werereceiving daily rifampin and daily clar-ithromycin or minocycline or dapsone.)

In two patients, followed for less than 4weeks, no judgement was made as to treat-ment response.

Of the two patients who developed Lucio’sphenomenon after initiating anti-microbialtreatment in our clinic, the one, Case 2, whodeveloped the reaction after discontinuingdapsone, responded without new lesions af-ter resumption of dapsone. The other, Case3, who developed Lucio’s phenomenon re-action after 7 months of daily dapsone andrifampin is a glaring exception to the usuallyfavorable outcome of microbicidal treat-ment. Her response to increased daily dosesof prednisone was good, with new lesionsceasing within 2 weeks, and no recurrencesin association with a slow tapering of theprednisone over 5 months.

Healing of ulcers. The ulcers usuallyhealed within 4 months, in 3 patients takingas long as 8 months, the length of time be-ing roughly proportional to ulcer size.

Follow up dataAs of December 31, 2004, 14 patients

were still being followed. Of the remainder,15 had been lost, and 1 was deceased after20 years of follow up. The length of followup has been as brief as less than 1 monthand as long as 35 years, mean 12.9 and me-dian 10. Five were followed for 1.3 years orless.

Erythema nodosum leprosumThirteen of the 30 patients, 7 women and

6 men, were known to have developedENL. In Case 2 ENL definitely precededthe onset of Lucio’s phenomenon. AlsoCase 4, who might have had mild ENL4 years prior to developing Lucio’s phe-nomenon, did develop typical ENL 37months after initiation of treatment withdaily rifampin and dapsone. ExceptingCase 2, the time of onset of the ENL rangedfrom 1 to 41 months after treatment wasstarted in our clinic, median 21 months, av-erage 22.1. Apart from this long mediantime of onset after initiation of treatment,the ENL in these patients did not differfrom the ENL seen in ordinary lepromatousleprosy. No patient had lesions of ENL atthe time of having new lesions of Lucio’sphenomenon.

Long term morbidityExcluding from analysis the 5 patients

followed for 1.3 years or less, some degreeof long-term morbidity has been experi-enced by 22 of the remaining 25 patients.Apart from ENL, the long-term morbidityobserved in these patients arose from threemechanisms. Two of these mechanisms, S-GPSI and venous insufficiency, appear to be a part of Latapi’s lepromatosis. Thethird mechanism producing long-term mor-bidity, scar formation, was the direct conse-quence of Lucio’s phenomenon. Secondaryto S-GPSI, 11 have experienced ongoingproblems with pathologic plantar callositiesand/or ulcers. Also secondary to S-GPSI, 5have physical impairment in the hands, in-cluding fissures, ulcerations, and bone re-sorption. Morbidity from muscle weakness


or contracture was rare, occurring only inCase 5, and consisted of soft tissue contrac-ture of the fascia and tendinous muscle inthe left knee complex. Recurrent leg ulcersfrom venous insufficiency have been an on-going problem for 10; 4 of these also hav-ing trophic problems in their feet. Scar for-mation led to hand and leg disabilities inone patient, Case 5.

Of the 14 who continue to be followed, 7have a disability grade 1 or 2 according tothe WHO grading system; 3 with a grade 1disability and 4 with a grade 2 disability.Those with grade 2 disability include onewith bilateral finger resorption, one withunilateral finger resorption, one with a re-solving plantar ulceration, and one (Case 5)with right hand partial amputation due to is-chemic changes.

Histologic changesHistologic material obtained from lesions

of Lucio’s phenomenon was available forreview in 22 patients. In 15 both H&E andadequately preserved Fite stained materialwas available, in 5 H&E only, and in 2 ade-quately preserved Fite stained tissue only.The common source of variation amongspecimens was the age of the lesion sampled.Most of the features have been described indetail and illustrated elsewhere (25, 26).

In all 22 patients the histologic materialdemonstrated foamy macrophages in thedermis in association with a few lympho-cytes. The volume of the dermis occupiedby the macrophages was small in 16 speci-mens, ranging from 2–10%, with a medianvalue of 5%. In the remaining 6, the volumeoccupied was larger, ranging from15–40%, with a median of 23%. In con-trast, in biopsy specimens obtained fromthe indurated, but not visible subcutaneousplaques present before the Lucio phenome-non in Cases 3 and 5, the volume of the in-filtrate occupied approximately 70 and 80%of the dermis, respectively. In their Lucio’sphenomenon lesions the volume of the der-mis occupied by macrophages was approx-imately 5–10% in both patients.

Epidermal necrosis was present in 18 andabsent in 2 but could not be evaluated in 2because of absent or insufficient epidermis.In the recent lesions, the necrotic epidermiswas of normal thickness but manifested theabsence of staining of nuclei, nuclear

ghosts, and early regeneration at the periph-ery, which was an epithelial tongue dissect-ing between the necrotic epidermis and thedermis. In older lesions, a new keratinizingepidermis was well developed, the necroticepidermis now located above the new stra-tum corneum, and identifiable by com-pacted nuclear ghosts in the former pricklecell layer and melanin in the former basalcell layer (Fig. 1d). Similarly, necrosis ofeccrine ducts and/or coils was present tosome degree in 16 and absent in 6. In theoldest lesions, the necrotic epidermis wasevidently exfoliated in the processing, andnecrotic eccrine structures had been ab-sorbed.

Intense passive congestion of vessels waspresent in 16 and absent in 4, but could notbe evaluated in 2. This was usually con-fined to the superficial dermis, but was pres-ent in the deep dermis or subcutis in 3. Ex-travasation of erythrocytes was present in12 and absent in 8, but could not be evalu-ated in 2.

In the medium sized vessels of the dermisand subcutis, endothelial proliferation wasidentified in 20, but could not present in 2.The proliferation ranged from mild to se-vere, frequently producing luminal occlu-sion, and was associated with thrombosis in7. Inflammatory cells with in these vesselswere few in number, suggesting that theterm “vasculosis” would be better than“vasculitis.” The generally sparse inflam-matory infiltrate was primarily lympho-cytic. Neutrophils or neutrophilic dust wereidentified in 6 of 22 specimens, but werenot associated with vascular changes, butinstead were infiltrating necrotic areas in 5,and in the subcutis in 1. Fibrinoid changewas present in 1 specimen.

Subcutaneous tissue was present in spec-imens from 18 patients. The area occupiedby the subcutis was estimated to be 20% orless than that of the dermis in 5, 20–50% ofthat of the dermis in 6, and 50% or more ofthat of the dermis in 7, respectively. All 18specimens had some degree of a lobularpanniculitis. This was considered to be fo-cal in 9, involving an estimated 15% or lessof the panniculus, moderate in 5, involving20–40%, and extensive in 4, involving50–80%. The nature of the infiltrate variedconsiderably, 8 with leprotic macrophagesand only a few lymphocytes, 9 with an ob-


vious mixture of leprotic macrophages andlymphocytes, and 1 with leprotic macro-phages and neutrophils, the latter infiltrat-ing between the lipocytes, apparently ignor-ing the vessels.

Concerning specimens with adequatelypreserved Fite stains, AFB and globi werefound in macrophages in the dermis in all17 specimens, as well as in the macro-phages in the subcutis of the 15 specimensso endowed. In all 15 specimens with bothendothelial proliferation and a Fite stain,bacilli in some of the proliferating endothe-lial cells were readily identified in all but 1,often with globi. Similarly, in all 17 speci-mens with a Fite stain, bacilli could befound in some non-proliferating endothelialcells. Bacilli were most difficult to find inendothelial cells in Case 3, probably theconsequence of 7 months of continuous an-timicrobial treatment

Histologic changes in large vessels, orvessels made large by pathologic changes,which we have chosen to call L-GV, werepresent in a total of 6 of the 22 (27%) pa-tients with Lucio’s phenomenon. In 2,Cases 3 and 5, the large vessel changeswere observed only in non-necrotic speci-mens, obtained before the onset of Lucio’sphenomenon. The fully developed L-GVconsisted of endothelial proliferation,macrophages infiltrating the media, andmacrophages infiltrating the adventitia.This fully developed change was found inCase 3, (Fig. 1a–c), and in lesions from 2other Lucio’s phenomenon patients. In oneof these latter 2, the changes were active,(Fig. 4b, and in the other the changes wereconsidered to be regressing (Fig. 4c). In-complete expression of the L-GV consistedof endothelial proliferation with a variabledegree of adventitial infiltration, as exem-plified by Fig. 4a, also found in Figs. 2a and 3a. A similar L-GV was found in 6 of70 (9%) of histologic specimens obtainedfrom lesions of ENL (Fig. 4d), and as anincipient change in 3 of 51 (6%) non-reactional lepromatous patients (data notshown). These incipient changes werefound in comparatively large subcutaneousvessels located near the dermis, and con-sisted of foci of endothelial proliferation inwhich AFB were identified, whereas nonewere found in non-proliferating endothe-lium. In Lucio-Latapi disease, ENL, and

non-reactional lepromatous leprosy, thevessels involved with L-GV were located inthe subcutis, or what was subcutis prior tolepromatous infiltration or connective tissueproliferation. The L-GV involved vesselswere largest in the Lucio-Latapi patients,smallest in the non-reactional lepromatousmaterial, and of intermediate size in speci-mens of ENL.

DISCUSSIONThe findings in the additional 20 patients

with Lucio’s phenomenon are in good ac-cord with the initial report of 10 such pa-tients (25) from this clinic. Hence the 30 pa-tients have been taken together in this re-port. The additional 20 patients and thefollow-up information add detail to thevariations in the clinical picture without al-tering its broad outlines. The one exceptionto this accord is the finding of large vesselinvolvement in the subcutis, where it wasnot found in a previous report (26). This fail-ure was not due to a lack of looking, butwas probably the result of inadequate sam-pling of the subcutis with the 4mm in diam-eter punch biopsy instruments, then in rou-tine use. This contrasts to the more gener-ous amounts, and greater depths, obtainedwith the 6mm punches, in common use inour clinic for the past 2 decades, as exem-plified by Fig. 1a.

What is being called L-GV is not a newpattern. For example, this pattern has beenpreviously observed in non-reactional lepro-matous specimens (7), as well as in specimensof ENL (17, 27). Also it has been observed andillustrated in Lucio’s phenomenon (10), andwas alluded to by Latapi and Zamora (15).The pattern is similar to, if not the same as,that of the “leprous phlebitis” reported byMukherjee and his associates (19, 20).

L-GV occurs in larger vessels, or in ves-sels made large by pathologic changes, pri-marily in the subcutis. L-GV, and what isinterpreted as its variants, was present in 4of the specimens from 22 Lucio’s phenom-enon patients with material available for re-view, and in 2 of the 3 pre-Lucio’s phenom-enon specimens available for review. How-ever, the importance of L-GV to thepathogenesis of Lucio infarcts, if any, is notknown.

An argument can be made to support thehypothesis that the L-GV is not important


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FIG. 4 (a). From Case 9, a Lucio’s phenomenon lesion. An obliquely sectioned, subcutaneous vessel show-ing extensive endothelial proliferation, and heavy adventitial infiltration, but little disturbance in the smooth mus-cle bundles. 20× objective. b) A panvasculitic vessel from the subcutis of a Lucio’s phenomenon lesion showingintimal proliferation, a chaotic infiltration of macrophages among the smooth muscle bundles, and infiltration inthe adventitia. c) A high power view of a large subcutaneous vessel which shows modest endothelial change,


to the pathogenesis of Lucio’s phenome-non. Because the pattern of L-GV also hasbeen seen in lesions of ENL (17, 27) (Fig. 4d),as well as in non-reactional lepromatousleprosy (7), and because it has similarities tothe leprous phlebitis reported by others (19,

20) it is not specific for either Latapi’s lepro-matosis or the Lucio reaction. Also, becauseits presence in Cases 3 and 5 were not di-rectly associated with necrotic lesions, it isnot a change necessarily leading to necrosis.In this context L-GV is most easily inter-preted as part of the vascular changesknown to be associated with leprosy, fromlarge muscular arteries, to arterioles, to cap-illaries, to venules, and on to large veins.Such changes have been reported by, amongothers, Fite (12), Coruh and McDougall (7),Kaur, et al. (14), Bansai, et al. (5), andMukherjee and his associates (19, 20).

An argument can be made to support thecontrary hypothesis of importance for L-GVin pathogenesis. Anoxia is a final cause oftissue necrosis, however diverse the respon-sible mechanisms. In patients with Lucio-Latapi disease, anatomical changes with thepotential of leading to anoxia have beendemonstrated at three levels of the vasculartree. Best described is the endothelial pro-liferation with lumen occlusion, with orwithout thrombosis formation, occurring inthe mid-sized vessels in the dermis of thenecrotic lesions (25, 26, 31), as confirmed in thepresent study. Also, swelling and parasitiza-tion, with lumen occlusion, of capillary en-dothelium has been found by electron mi-croscopy in 3 of 3 specimens of clinicallynormal skin (33), i.e., Latapi’s lepromatosis,from patients with Lucio’s phenomenon,and could well be widespread. The subcu-ticular L-GV found in the present study inboth Lucio’s phenomenon and Latapi’s lep-romatosis is a third anatomical change thatcould contribute to anoxia; this change, iffocal, could also be more prevalent than hasbeen observed. All of these changes actingsynchronously might result in an ischemia

sufficient to produce necrosis, whereas anyone by itself would be less likely do so. Inaddition, the circulating immune complexesassociated with Lucio’s phenomenon (23)might interact with the anatomical changesin ways that lead to necrosis.

Perhaps the changes of the L-GV are bet-ter developed Latapi’s lepromatosis, be-cause this difficult to diagnose lepromatouscondition may give more time for bacterialproliferation and for a granulomatous vas-culitis to develop.

Three retrospective findings were not an-ticipated, but emerged only when the com-paratively large numbers of patients re-ported here were gathered together. 1) Thenear parity of the genders is in contrast tothe expected male preponderance, 2 to 1, inlepromatous disease (21). 2) The absence ofS-GPSI in 7 patients was not anticipated tobe this common in Latapi’s lepromatosis.3) The median time of onset of ENL, 21months after initiating treatment, appears todiffer considerably, and perhaps signifi-cantly, from the 12 months median time ob-served in this clinic (unpublished data).Good explanations for these three unex-pected findings are not available.

Clinically, the ischemic infarcts of Lu-cio’s phenomenon were of a uniform char-acter, varying in size and extent, but alwaysof the same kind, or, in other words, amonomorphic response. Accompanying ul-cers, erosions and bullae, were clearly sec-ondary to the infarct.

The report by Diogenes, et al. (9) and ourexperience with Case 2, raises the possibil-ity of the diagnosis of Latapi’s lepromatosisin the absence of Lucio’s phenomenon.Usually a diagnosis of Latapi’s lepromato-sis is made after the fact of Lucio’s phe-nomenon. Which findings or combinationof findings might be considered as criteriafor a diagnosis of Latapi’s lepromatosis inthe absence of Lucio’s phenomenon?

Either of two findings could be regardedas a sine qua none for this diagnosis. Dif-


←spotty infiltration in the wall, and involvement of the adventitia. The process appears to be old and regressing.This impression is supported by the absence of a defined muscular layer, and by the several lines of “hash marks”at different levels in the wall, suggesting repeated reduplication of the internal elastic lamina, (block not avail-able for definitive staining). 40× objective. d) A high power view of a subcutaneous vessel in an ENL lesion, giv-ing an exemplary demonstration of the features of lepromatous-granulomatous vasculitis (L-GV), that is, en-dothelial proliferation, infiltration of macrophages between smooth muscle bundles, and adventitial infiltration.20× objective.

fuse non-nodular infiltration is one; theother is heavy endothelial parasitization byM. leprae. Neither finding is specific forLatapi’s lepromatosis, but the presence ofdermal nodules or the absence of endothe-lial parasitization virtually excludes thepossibility of Latapi’s lepromatosis.

Three other distinct findings could be re-garded as highly suggestive of Latapi’s lep-romatosis. These are 1) telangiectasias, ei-ther eruptive or as mats on the face andchest, 2) palpable but not visible subcuta-neous plaques, and 3) as manifestations ofdiffuse infiltration, widening of the nasalroot, poorly defined induration of the facialcheeks, with or without erythema, andswelling of the backs of the hands.

In the presence of the two “sine quanon’s” other common changes could be re-garded as supportive of a diagnosis of Lat-api’s lepromatosis. These include completeeyebrow and or eyelash alopecia, nasal sep-tum perforation, and significant S-GPSIwith little motor change.

In lepromatous patients who presentwithout nodular change and who haveheavy parasitization of endothelial cells, (inour experience those who present withspontaneous ENL (24)), findings whichpoint away from a diagnosis of Latapi’s lep-romatosis include normal eyebrows andeyelashes, mild or absent rhinitis, and ocu-lar involvement.

Five biopsy specimens obtained beforethe onset of Lucio’s phenomenon were ex-amined by one of us, three being availablefor review. In all four with a Fite stain, en-dothelial parasitization by M. leprae wasevident. As demonstrated by hematoxylinand eosin, three histologic patterns wereidentified, and each pattern could be relatedto the clinical findings at the biopsy site. InCases 1 and 2, where the specimen chosenwas from clinically normal skin, the infil-trate was scant, and with little if any otherinflammatory change, aptly described as“apparently normal.” In Case 4, with theclinical findings of erythematous nodules, adistinct lymphocytic infiltrate was associ-ated with foamy macrophages. In cases 3and 5, the specimens being obtained fromnot visible, non-tender, indurated subcuta-neous plaques, well developed vascularchanges were associated with a heavy infil-trate of macrophages.

Two of the 3 pre-Lucio specimens avail-able for review, from cases 3 and 5, demon-strated endothelial proliferation with lumenocclusion, and were obtained 7 and 5months, respectively, before the onset onLucio’s phenomenon. In the third specimen,obtained 4 years before the onset of the Lu-cio’s phenomenon, no such vascular changewas evident.

The most conspicuous disagreement inthe literature concerning Lucio’s phenome-non is in regard to its histologic pattern,leukocytoclastic vasculitis (LCV): LCV yes(2, 18, 31) or LCV no (10, 22, 25)? The review ofour biopsy material is in accord with ourprevious conclusion that the histologic pat-tern is not that of LCV (25). The most likelyexplanation for the disagreement is differ-ing criteria for what constitutes LCV. An-other possibility is the intellectual difficultyin dissociating or uncoupling the idea of aputatively immune complex disorder ofskin (23) from the histologic pattern of LCV.The histologic pattern called LCV is thatfound in “palpable purpura” and is the samewhatever disease may be producing the le-sions of “palpable purpura.” The lesions of“palpable purpura” were not found in anyof these 30 patients.

Clinically, a variety of septic infarcts andthrombotic syndromes (4) may mimic theinfarct of Lucio’s phenomenon, beinghemorrhagic and having serrated borders.In addition, one recent case report givesstrong evidence that other vasculitic condi-tions may closely mimic Lucio’s phenome-non. Tang and Yosipovitch (32), in their re-port of an acute Churg-Strauss syndrome,have in their clinical photograph (their fig.1) illustrated changes perfectly consistentwith the serrated, hemorrhagic infarcts ofthe Lucio reaction. In the same report is aphotomicrograph (their fig. 2) which showsextravasation of erythrocytes, and in our in-terpretation, congestion of superficial ves-sels, and a necrotic epidermis, identified inthe legend as “scale crust,” a pattern look-ing much like our Fig. 1d. Viewed in thisperspective, the second episode of infarc-tions in Case 9, would be best regarded asbeing a Lucio’s phenomenon-like tissue re-sponse of unknown cause, not a true Lu-cio’s phenomenon.

Comfort may be taken from this series,where by the time of development of


Lucio’s phenomenon, overt clinical signs oflepromatous leprosy, without exception,were present. Conversely, anxiety may arisefrom this series, where, in some cases, thediagnosis of leprosy was not made until theLucio phenomenon occurred, even thoughpreceding characteristic signs and symp-toms, although seen and heard by physi-cians, were not interpreted as suggestingthe possibility of leprosy.

Acknowledgment. Many physicians have pro-vided help in making this report possible. For access toclinical data and histologic material on some of the pa-tients, the authors are indebted to Drs. Lewis Bowman,Randy Burke, and Keith Carlson. Dr. Nancy Warnergave expert help with photomicrographs. Dr John T.Crissey provided valuable advice and printed the pho-tographs in “black and white.” Dr. Claudia Renn trans-lated reference number 1.

REFERENCES1. ALMEIDA, H. L., JANNKE, H. A., RIVITTI, E. A., MI-

CARETTA, S., and CASTRO, S. N. PostinfektiosesLucio-phanomen bei diffuser lepra. Hautarzt 51(2000) 945–949.

2. ANG, P., YONG-KWANG, T., SEE-KET, N., andCHEW-SWEEN, S. Fatal Lucio’s phenomenon in 2patients with previously undiagnosed leprosy. J.Am. Acad. Dermatol. 48 (2003) 958–961.

3. ARNOLD, H. L., and SLOAN, N. R. Lucio’s spottedleprosy (diffuse lepromatous leprosy of Mexico):report of a case in Hawaii. Int. J. Lepr. Other My-cobact. Dis. 19 (1951) 23–27.

4. BAKOS, L., CORREA, C., BERGMANN, C.,BONAMIGO, R. R., and MULLER, L. F. B. An-tiphospholipid antibodies throbotic syndrome mis-diagnosed as Lucio’s phenomenon. Int. J. Lepr.Other Mycobact. Dis. 64 (1996) 320–323.

5. BANSAI, R., KAUR, S., KUMAR, B., SHARMA, V. K.,KATARIYA, S., CHAKRAVARTI, R. N., and BUSHAR-NAMATH, S. R. Venous involvement in leprosy: avenogrophic and histopathological correlation, Int.J. Lepr. Other Mycobact. Dis. 55 (1987) 499–506.

6. BERNADAT, J. P., FAUCHER, J. F., and HUERRE, M.Diffuse lepromatous leprosy disclosed by cuta-neous vasculitids. Ann. Dermatol. Venereol.. 123(1996) 21–23.

7. CORUH, G., and MCDOUGALL, A. C. Untreatedlepromatous leprosy: histopathological finding, incutaneous blood vessels. Int. J. Lepr. Other My-cobact. Dis. 43 (1979) 500–511.

8. DERBES, V. J., SAMUELS, M., WILLIAMS, O. P., andWALSH, J. J. Diffuse leprosy: case in a Louisiananegro. Arch. Dermatol. 81 (1960) 210–224.

9. DIOGENES, M. J. N., DE MORALES, R. M., S. DE

TOME, G., DA CUNHA, M. B., and DE C. B. NETO,C. The Lucio-Alvarado-Latapi form of LeprosyLep. Rev. 72 (2001) 360–362.

10. DONNER, R. S., and SHIRELY, J. A. The “Luciophenomenon” in diffuse leprosy. Ann. Iutern.Med. 67 (1967) 831–836.

11. DROSOS, A. A., BRENNAN, P. J., ELISAF, M. S., STE-FANOU, S. G., PEPADIMITRIOU, C. S., and MOUT-SOPAOULOS, H.M. Specific antigen and antibodyto Mycobacterium leprae in the cryoprecipitate ofa patient with Lucio phenomenon. Rheumatol. Int.6 (1986) 93–94.

12. FITE, G. L. The vascular lesions of leprosy. Int. J.Lepr. Other Mycobact. Dis. 9 (1941) 193–202.

13. KAMP, H., LEIKER, D. L., and FRENKEN, J. H. Therelationship between the Lucio phenomenon andcutaneous allergic vasculitis (Ruiter). Int. J. Lepr.Other Mycobact. Dis. 30 (1962) 138–151.

14. KAUR, S., WAHI, P. L., CHAKRAVARTI, R. N., SODHI,J. S., VADHWA, M. B., and KHERA, A. S. Periph-eral vascular defect in leprosy. Int. J. Lepr. OtherMycobact. Dis. 44 (1976) 332–339.

15. LATAPI, F., and ZAMORA, A. C. The “spotted”leprosy of Lucio ( la lepra “manchada” de Lucio).Int. J. Lepr. Other Mycobact. Dis. 16 (1948)421–437.

16. LUCIO, R., and ALVARADO, Y. Opusculo sobre elmal de San Lazaro o elefanciasis de los Griegos.M. Murguia y Cia, Mexico, 1852, 53 pp.

17. MABALAY, M. C., HELWIG, E. B., TOLENTINO, J. G.,and BINFORD, C. H. The histopathology andhistochemistry of erythema nodosum leprosum.Int. J. Lepr. Other Mycobact. Dis. 33 (1965)28–49.

18. MOSCHELLA, S. L. The lepra reaction with necro-tizing skin lesians: A report of six cases. Arch.Dermatol. 95 (1967) 565–575.

19. MUKHERJEE, A., GIRDHAR, B. K., and DESIKAN, K.V. Leprous Phlebitis. Int. J. Lepr. Other My-cobact. Dis. 48 (1980) 48–50.

20. MUKHERJEE, A., GIRDHAR, B. K., MALVIYA, G. N.,RAMU, G., and DESIKAN, K. V. Involvement ofsubcutaneous veins in lepromatous leprosy. Int. J.Lepr. Other Mycobact. Dis. 51 (1983) 1–6.

21. NEWELL, K. W. An epidemiologist’s view of lep-rosy. Bull. WHO 37 (1966) 827–857.

22. PURSELEY, T. V., JACOBSEN, R. R., and APISARN-THANARAX, P. Lucio’s phenomenon. Arch. Der-matol. 116 (1980) 201–204.

23. QUISMORIO, F. P., REA, T., CHANDOR, S., LEVAN,N., and FRIEU, G. Lucio’s phenomenon: and im-mune complex deposition syndrome in leproma-tous leprosy. Clin. Immunol. Immunopathol. 9(1978) 184–193.

24. REA, T. H., and LEVAN, N. E. Erythema nodosumleprosum in a general hospital. Arch. Dermatol.111 (1975) 1575–1580.

25. REA, T. H., and LEVAN, N. E. Lucio’s phenome-non and diffuse non-nodular lepromatous leprosy.Arch. Dermatol. 114 (1978) 1023–1028.

26. REA, T. H., and RIDLEY, D. S. Lucio phenomenon:A comparative histologic study. Int. J. Lepr. 47(1979) 161–166.


27. RIDLEY, D. S., REA, T. H., and MCADAM, K. P. W.J. The histology of erythema nodosum leprosum.Variant forms in New Guineans and other ethicgroups. Lepr. Rev. 52 (198)1 65–78.

28. ROMERO, A., IBARRA, A. B., and FALLAS, M. Clini-cal study of lepromatous leprosy in Costa Rica. Int.J. Lepr. Other Mycobact. Dis. 17 (1949) 27–33.

29. SAOJI, V., and SALODHAR, A. Lucio leprosy withlucio phenonenon. Indian J. Lepr. 73 (2001)267–272.

30. SHESKIN, J. Diffuse lepromatosis of the Lucio-Alvarado-Latapi with Lucio phenomenon: first casein the Near East. Rev. Leprol. 13 (1982) 651–656.

31. SOUZA, C. S., ROSELINO, A. M., FIGUEIREDO, F.,and FOSS, N. T. Lucio’s phenomenon:clinical andtherapeutic aspects Int. J. Lepr. Other Mycobact.Dis. 68 (2000) 417–25.

32. TANG, M. B. Y., and YOSIPOVITCH, G. AcuteChurg-Strauss Syndrome in an asthmatic patientreceiving montelukast therapy. Arch. Dermatol.139 (2003) 715–717.

33. TURKEL, S. B., VAN HALE, H. M., and REA, T. H.Ultrastructure in leprosy. Int. J. Lepr. Other My-cobact. Dis. 50 (1982) 164–171.

34. WONG, W. S. Leprosy presenting as modular vas-culitis. (Letter). Brit. J. Rheumatol. 26 (1987) 398.


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