Import of an Extinct Disease?

OBSERVATION Pinta in Austria (or Cuba?) Import of an Extinct Disease?

Ingrid Woltsche-Kahr, MD; Bruno Schmidt, PhD; Werner Aberer, MD; Elisabeth Aberer, MD

Background: Pinta, 1 of the 3 nonvenereal treponema- detection of spirochetes in the trunk lesion indicated early toses, is supposed to be extinct in most areas in South and secondary syphilis, but an extensive case history and the Central America, where it was once endemic. Only scat- clinical appearance fulfilled all criteria for pinta. tered foci may still remain in remote areas in the Brazilian rain forest, and the last case from Cuba was reported in 1975. Conclusion: The acquisition of a distinct clinical en- tity, pinta, in a country where it was formerly endemic Observation: A native Austrian woman, who had lived but now is believed to be extinct raises the question of for 7 years in Cuba and was married to a Cuban native, whether the disease is in fact extinct or whether syphilis developed a singular psoriasiform plaque on her trunk and pinta are so similar that no definite distinction is pos- and several brownish papulosquamous lesions on her sible in certain cases. palms and soles during a visit to her home in Austria. Positive serological findings for active syphilis and the Arch Dermatol. 1999;135:685-688

HE NONVENEREAL trepone- after the appearance of pintids), lesions matoses yaws, endemic marked by vitiligolike depigmentation are syphilis (bejel), and pinta the leading feature. These lesions are not are caused by an organism believed to be infectious. Histopathologi- that is morphologically and cal investigations show moderate acan- Tantigenically identical to the causative agent thosis, spongiosis, sometimes hyperkera- of venereal syphilis, Treponema pallidum. tosis and hypergranulosis, and liquefaction However, they differ significantly from generation of the basal layer in the epi- syphilis in their mode of transmission, epidermis, and a perivascular dermal infil- demiology, and clinical manifestation. trate composed of lymphocytes, plasma Pinta, which is endemic only in the cells, and neutrophils in the upper der- western hemisphere, is the most benign mis. The main reservoir of pinta is young spirochetal disease, showing only skin adults, who have chronic skin lesions. Di- manifestations and occasionally mild sys- rect skin-to-skin contact is the likely temic symptoms (Table).1 The lesions of mechanism of transmission. pinta are characterized by first hyperkera- Several reports of cases of yaws and totic and later dyschromic eruptions. Like bejel imported to Europe as well as the venereal syphilis, pinta chronically re- ever-increasing ease of travel to the world’s lapses. The primary lesion appears as a remotest areas legitimate the demand to small papule or erythematous macule 7 to consider a diagnosis of nonvenereal trepo- 70 days after inoculation and extends nematoses in certain clinical situations. within several weeks to an erythematous Lack of evidence in a recent case that pinta From the Divisions of Allergy infiltrated plaque of up to 12.5 cm in di- is completely eradicated in areas of Cen- and Venereology ameter. Several months to years after ap- tral America where it was once endemic2 (Drs Woltsche-Kahr and pearance of the initial lesion, small scaly seemed to justify this diagnosis in a case W. Aberer) and General papules that enlarge to psoriasiform that fulfilled all historical, clinical, and se- Dermatology (Dr E. Aberer), plaques, “pintids,” may develop. These rological criteria of this disease. Department of Dermatology, University of Graz, highly infectious secondary lesions may be Graz, Austria; and sparse or numerous and, after healing, REPORT OF A CASE Ludwig-Boltzmann Institute, leave areas of gray, brown, or slate blue hy- Hospital of Vienna-Lainz, perpigmentation or depigmentation. In the A 28-year-old white Austrian woman, who Vienna, Austria (Dr Schmidt). late stage of pinta III (months to 10 years was married to a native Cuban and had

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Characteristics Pinta Venereal Syphilis Transmission Ͼ95% Nonsexually (extragenital pattern) Ͼ95% Sexually; hematogenous; diaplacental (3-9 mo) Clinical manifestations Stage I Extragenital; erythematous infiltrated plaque Genital/extragenital; indolent ulcer; regional lymphadenopathy Stage II Pintids (small, scaly papules that enlarge to psoriasiform Fever, joint pain, lymphadenopathy, exanthema, plaques with peripheral accentuation); no systemic condylomata lata, corona veneris, “plaques symptoms muqueuses,” angina specifica, alopecia areolaris specifica, and luetic leukoderma Stage III Vitiligolike depigmentation; no involvement of other Gummata; involvement of skin, bones, central nervous organs system, and visceral organs (liver, kidney, etc) Histopathology Histological criteria for the differentiation of Histological criteria for the differentiation of treponematoses are unreliable: acanthosis, treponematoses are unreliable: acanthosis, intraepidermal neutrophilic microabscesses, upper intraepidermal neutrophilic microabscesses, upper dermal inflammatory infiltration around blood vessels dermal inflammatory infiltration around blood vessels Serology No serologic test can distinguish between the No serologic test can distinguish between the treponematoses: TPHA, FTA-ABS, VDRL, IgM ELISA, treponematoses: TPHA, FTA-ABS, VDRL, IgM ELISA, immunoblot† immunoblot† Molecular techniques Treponema differ in a single nucleotide? Treponema differ in a single nucleotide? Epidemiology Endemic foci and isolated cases Worldwide Therapy Յ2-y duration: penicillin G benzathine, 2.4 million U Յ2-y duration: penicillin G benzathine, 2.4 million U intramuscularly, 1 application; Ͼ2-y duration: intramuscularly, 1 application; Ͼ2-y duration: penicillin G benzathine, 2.4 million U intramuscularly, penicillin G benzathine, 2.4 million U intramuscularly, 3 times in 1 wk (in case of allergy to penicillin: 3 times in 1 wk (in case of allergy to penicillin: doxycycline, erythromycin) doxycycline, erythromycin)

*From Koff and Rosen.1 †TPHA indicates Treponema pallidum hemagglutination; FTA-ABS, fluorescent treponemal antibody absorption test; and ELISA, enzyme-linked immunosorbent assay.

Figure 2. Close-up view showing a hyperkeratotic annular plaque.

Figure 1. A single nummular plaque in the left thoracolumbar region. denied having had any extramarital relations in the recent past. lived for the past 7 years in an urban area of Cuba, de- Clinical inspection of the patient disclosed a soli- veloped a solitary erythematosquamous plaque on the left tary erythematous, hyperkeratotic annular plaque of 2.5 side of her trunk. This lesion had lasted for almost 1 month cm in diameter in the left thoracolumbar area, resem- when she was examined at our outpatient clinic. She did bling tinea corporis, a psoriatic plaque, granuloma an- not remember any fever, tick bites, changes in oral or geni- nulare, or hyperkeratotic lichen planus (Figure 1 and tal mucous membranes, joint pain, or lymphadenopa- Figure 2). Furthermore, several discrete erythemato- thy. On questioning, she told us that her husband had squamous lesions on the palms and soles (Figure 3), observed a similar lesion in his right subaxillary region each about 1 cm in diameter, were found; the patient had about 4 months before but that it had disappeared spon- not been aware of them. The remaining skin as well as taneously; a routine test of her husband’s serum before oral and genital mucous membranes showed no abnor- minor surgery in Cuba had disclosed a positive serologi- malities; the lymph nodes were not enlarged, and no alo- cal test result for syphilis, and the husband had then been pecia or any other signs of secondary syphilis could be treated with penicillin. Both our patient and her spouse detected.

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47 kd

Figure 3. Several brownish red papulosquamous lesions, each about 0.5 to 1 cm in diameter, on the palms. 17 kd 15.5 kd

Figure 5. Western blots showing nearly identical bands in serum from our patient with pinta (lane 1) and serum from patients with syphilis II (lane 9), syphilis I (lanes 2-6 and 8), and latent syphilis (lane 10). Lane 7 contains serum from a healthy person without syphilis.

T pallidum hemagglutination test, 1:5120; fluorescent treponemal antibody absorption test for IgM and IgG; Cap- tia-Syphilis-M IgM enzyme-linked immunosorbent assay (Biotech; Gull Laboratory, Bad Homburg, Ger- many); and VDRL test, 1:32. Western blot analysis with a T pallidum IgM and IgG test kit (Marblot; VIRAMED, Munich, Germany) showed bands of 15.6, 17, 47, 61, and Figure 4. Numerous spirochetes in the epidermis of the hyperkeratotic trunk 83 kd in the IgG blot and 17, 37, 41, and 47 kd in the lesion (immunoperoxidase method with polyclonal anti–Treponema pallidum IgM blot, a pattern typical of Treponema (Figure 5). As antibody, oil immersion, original magnification ϫ1000). controls, serum samples from 8 patients with syphilis and 1 healthy person were investigated. Serum from our pa- Wound serum was harvested from the hyperkera- tient (lane 1) demonstrated bands nearly identical to those totic plaque on the trunk after mechanical erosion of the of serum from patients with syphilis I and II. plaque. On dark-field microscopy, multiple typical trepo- The patient was treated with 2.4 million U of peni- nemes could be observed performing their characteris- cillin G benzathine according to the World Health Or- tic bending and rotational movements. ganization regimen for the treatment of early syphilis. The Histopathological examination was done on a 4-mm lesions disappeared within a few days, and markers of punch biopsy specimen from the plaque after formalin active syphilis (VDRL) became negative. fixation and paraffin embedding. Hematoxylin-eosin staining showed a psoriasislike picture with parakeratosis, ac- COMMENT anthosis, spongiosis, and an infiltration of lymphocytes, eosinophils, and abundant neutrophils in the Nonvenereal treponematoses differ significantly from ve- epidermis forming intraepidermal abscesses. There was nereal syphilis in their mode of transmission, epidemio- edema of the papillary dermis and an obscured epidermal- logical characteristics, and clinical appearance, but not dermal interface. In the dermis there was a patchy peri- in their serological test results and treatment recommen- vascular and interstitial infiltrate of lymphocytes, plasma dations. The typical clinical manifestations of one of the cells, neutrophils, and some eosinophils. Blood vessels nonvenereal treponematoses, pinta, however, closely re- showed dilation but no substantial endothelial swell- semble those of syphilis (Table). Treponema carateum, the ing. Several melanophages were present in the dermis. cause of pinta, is morphologically and antigenically in- Furthermore, abundant treponemes were detectable in distinguishable from T pallidum.1 In fact, despite ad- the epidermis by silver staining and by an immunoper- vanced technical developments in the last decade, no dif- oxidase staining on cryostat sections with the use of a ferences between the subtypes of treponema can be polyclonal anti–T pallidum antibody in a 1:200 dilution detected by Western blot or Southern blot hybridiza- (Biodesign International, Kennebunk, Me) (Figure 4). tion techniques. Treponema carateum cannot be cul- The following specific and nonspecific serological tured in vitro but can be transmitted to chimpanzees.3 test results for Treponema were positive in our patient: Noordhoek et al4 reported that the T pallidum subspe-

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 cies pertenue and pallidum differed by a single nucleo- not been diagnosed in Cuba for many years (e-mail com- tide; these findings, however, could not be replicated by munication, May 11, 1998). others. It has been suggested that the variations in clini- There is, however, no proof of pinta’s extinction, cal expression are entirely caused by divergent environ- since patients with pinta may remain contagious for pro- mental conditions, such as temperature.5 longed periods, may harbor subclinical disease, and do Since 1975, pinta has seemed to be extinct world- not develop lifelong immunity. Because the ease of worldwide except in a few scattered areas in the Brazilian rain wide travel can aid in their dissemination, nonvenereal forest.2,6,7 Yet, any textbook on dermatovenereology still treponematoses should therefore still be considered in describes this disease, and the medical student has to learn differential diagnoses. the differential diagnosis. Our patient fulfills all the criteria of pinta stage I to Accepted for publication December 1, 1998. II, with the typical primary skin lesion on the thoraco- We thank the following persons, in alphabetical or- lumbar area in the form of an annular hyperkeratotic der, for information concerning the current prevalence of plaque, and secondary papulosquamous lesions on the pinta: Luiz G. M. Castro, MD, Sa˜o Paulo, Brazil; G. Kouri, palms and soles, spirochetes within the lesion, and se- MD, Instituto Pedro Kouri Ministeroi de Salud Publica, Ha- rological findings indicative of second-stage syphilis. In vana, Cuba; D. Petzold, MD, Society for Sexually Trans- contrast, in syphilis II, symmetrical lesions are present, mitted Diseases, Heidelberg, Germany; G. P. Schmid, MD, and on histological examination, swelling and prolifera- MSc, Centers for Disease Control and Prevention, Atlanta, tion of endothelial cells and no melanophages but epi- Ga; and S. Talhari, MD, Department of Dermatology, In- thelioid and giant cells are seen. Neutrophilic microab- stitute of Tropical Medicine, Manaus, Brazil. scesses are more often described in yaws. The patient, Corresponding author: Elisabeth Aberer, MD, like her husband, obviously acquired her disease in an Department of Dermatology, University Graz, Auenbrug- area in which pinta was once endemic. Yet, neither the gerplatz 8, A-8036 Graz, Austria (e-mail: elisabeth patient nor her husband suffered from the typical signs [email protected]). of stage I syphilis. In such a case the closest diagnosis is pinta. We therefore conclude that if a disease such as pinta REFERENCES still does exist in Cuba, our patient suffered from that disease and did import it to Europe. If, however, the dis- 1. Koff AB, Rosen T. Nonvenereal treponematoses: yaws, endemic syphilis and pinta. ease is extinct—except perhaps for a few scattered foci J Am Acad Dermatol. 1993;29:519-535. in the South American rainforest—why do we still bur- 2. Castro LG. Nonvenereal treponematoses. J Am Acad Dermatol. 1994;31:1075-1076. den our medical knowledge with such an outdated his- 3. Chandler FW Jr, Kaufmann AF, Kuhn US. The histopathology of experimental pinta torical term? in the chimpanzee. J Invest Dermatol. 1972;58:103-108. Nonvenereal treponematoses constituted a major 4. Noordhoek GT, Hermans PWM, Paul AN, et al. Treponema pallidum subspecies pallidum (Nichols) and Treponema pallidum subspecies pertenue (CDC 2575) health problem for many underdeveloped countries be- differ in at least one nucleotide: comparison of two homologous antigens. fore mass treatment programs were initiated in the Microb Pathogenesis. 1989;6:29-42. 1950s.8,9 No further cases of pinta have been reported to 5. Hardy PH. Prospects for improved laboratory diagnosis of treponemal infec- the World Health Organization from Mexico or Colom- tions and species differentiation. Rev Infect Dis. 1985;7:300-303. 10 6. Sosa-Martinez J, Peralta S. An epidemiologic study of pinta in Mexico. Am J Trop bia since 1979. The Centers for Disease Control and Pre- Med. 1952;10:556-565. vention in Atlanta, Ga, and the Pan American Health Or- 7. Edmundson WF, Rico AL, Olansky S. A study of pinta in the Trepalcatepec Ba- ganization in Washington, DC, have received no reports sin, Michoacan, Mexico. Am J Syphilol. 1953;37:201-225. of pinta from Cuba in the past 20 years (G. P. Schmid, 8. Arslanagic N, Bokonjic M, Macanovic K. Eradication of endemic syphilis in Bosnia. MD, MSc, Centers for Disease Control and Prevention, Genitourin Med. 1989;65:4-7. 9. Antal GM, Causse G. The control of endemic treponematoses. Rev Infect Dis. e-mail communication, May 11, 1998). Moreover, ac- 1985;7(suppl 2):220-226. cording to G. Kouri, MD, of the Instituto Pedro Kouri 10. Falabella R. Nonvenereal treponematoses: yaws, endemic syphilis and pinta. Ministeroi de Salud Publica in Havana, Cuba, pinta has J Am Acad Dermatol. 1994;31:1075.

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