International http://std.sagepub.com/ Journal of STD & AIDS
Malignant Lues in an immunocompetent patient João Alves, Ana Marta António, Diogo Matos, Ricardo Coelho and Pedro Cachão Int J STD AIDS published online 11 July 2014 DOI: 10.1177/0956462414544162 The online version of this article can be found at: http://std.sagepub.com/content/early/2014/07/11/0956462414544162
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Int J STD AIDS OnlineFirst, published on July 11, 2014 as doi:10.1177/0956462414544162
Case report
Malignant Lues in an immunocompetent patient
International Journal of STD & AIDS 0(0) 1–3 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0956462414544162 std.sagepub.com
Joa˜o Alves, Ana Marta Anto´nio, Diogo Matos, Ricardo Coelho and Pedro Cacha˜o
Abstract Malignant Lues is a rare form of secondary syphilis mostly associated with HIV infection. It is an uncommon presentation of syphilis even rarer in immunocompetent patients. We present the case of a 57-year-old homosexual man referred to our department due to a 4-month history of a disseminated, slightly painful, nodular-ulcerative cutaneous eruption associated with low-grade fever, malaise and asthenia. Regarding the clinical features and serological and histopathological findings, the diagnosis of syphilis maligna was assumed. Serology for HIV was repeatedly negative. This case is interesting, not only because a very uncommon form of secondary syphilis was identified but also for being diagnosed in an immunocompetent patient. Lack of awareness of this type of presentation delays the diagnosis and treatment, leading to an increase in morbidity and spread of infection.
Keywords Syphilis (Treponema pallidum), bacterial disease Date received: 18 May 2014; accepted: 23 June 2014
Malignant Lues is a rare form of secondary syphilis mostly associated with HIV infection.1 It is characterised by polymorphous, disseminated, papulonodular cutaneous lesions, typically ulcerated and covered by rupioid crust. Associated systemic findings are common.2 It is an unusual presentation of syphilis even rarer in immunocompetent patients.3 A 57-year-old homosexual man, with no medical history was referred to our department due to a 4-month history of a disseminated, slightly painful, nodularulcerative cutaneous eruption associated with lowgrade fever, malaise and asthenia. The patient reported unprotected sex with one male partner in the last 4 years. The skin examination showed isolated, rounded, well demarcated, erythematous-violaceous, tender nodules and plaques of varying sizes located on head, neck, trunk and limbs, sparing palms, soles and mucous membranes. Some lesions were ulcerated and covered by rupioid brown crusts (Figure 1). There was no lymphadenopathy or palpable hepatosplenomegaly. The neurological examination was normal. The suspected clinical diagnoses included cutaneous lymphoma, syphilis, pyoderma and systemic mycosis. Laboratory analysis showed a slightly elevated erythrocyte sedimentation rate (78 mm/1st hour) with no other
alteration, including liver and kidney function tests. Serologic tests revealed a high titre of RPR (>128) and TPHA (>5120). Serology for HIV, hepatitis B and C were negative. Immunophenotyping of blood lymphocytes was normal, including the CD4 cells count. Immunoglobulins levels were within the normal range. Skin biopsy was performed and revealed a diffuse dermal inflammatory infiltrate composed by plasma cells, histiocytes and lymphocytes, forming granulomas on deeper dermis (Figure 2). These aspects were compatible with a late secondary syphilis. Given the history, clinical examination and histological features, the diagnosis of syphilis maligna was assumed. Having the late symptomatology, severity, rarity and presence of systemic symptoms, the patient was treated with benzathine penicillin 2.4 million units weekly intramuscularly for 3 weeks. An excellent clinical response was observed. After 6 weeks, he was Department of Dermatology and Venereology, Garcia de Orta Hospital, Almada, Portugal Corresponding author: Joa˜o Vı´tor Pina Alves, Department of Dermatology and Venereology, Garcia de Orta Hospital, Av. Torrado da Silva, 2801-951 Almada. Email: [email protected]
Downloaded from std.sagepub.com at Umea University Library on September 5, 2014
XML Template (2014) [9.7.2014–12:23pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/STDJ/Vol00000/140136/APPFile/SG-STDJ140136.3d
(STD)
[1–3] [PREPRINTER stage]
2
International Journal of STD & AIDS 0(0)
Figure 1. Rounded, erythematous-violaceous, nodules and plaques located on neck, trunk and superior limbs. Ulcerations covered by rupioid crust on arms (b and c).
Figure 2. Diffuse dermal inflammatory infiltrate, predominantly perivascular, composed by large numbers of plasma cells, histiocytes and lymphocytes, forming granulomas on deeper dermis (a – hematoxylin and eosin 40; b – hematoxylin and eosin 400).
asymptomatic and had only residual hyperpigmented macules. Three months later, RPR value remained unchanged. At this time, a lumbar puncture was performed which was negative for neurosyphilis. The treponemal IgM test was also negative. Patient has remained on follow-up and 1 year after therapy a 4fold decrease in RPR was observed. HIV was repeatedly negative. Serologic tests performed to his sexual partner diagnosed a latent syphilis. The term ‘malignant’ was used in association with secondary syphilis by Bazin in 1859 and has been used to describe the grotesque clinical findings. People of
poor health, malnourished and alcoholics were commonly affected.2 Currently, most cases have been described in intravenous drug abusers and, mainly, in HIV-infected patients.3 The pathogenesis seems to depend on the host rather than on the causative agent. This is because, as in our case, patients with malignant syphilis have acquired the infection from persons with the routine manifestations of syphilis.2 The incubation period varies from 6 weeks to 1 year following primary infection. Disease onset is characterised by the prodrome of fever, arthralgia, myalgia, headache and photophobia.2 Skin lesions start as
Downloaded from std.sagepub.com at Umea University Library on September 5, 2014
XML Template (2014) [9.7.2014–12:23pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/STDJ/Vol00000/140136/APPFile/SG-STDJ140136.3d
(STD)
[1–3] [PREPRINTER stage]
Alves et al.
3
papules that evolve into nodules and pustules; within a few days the lesion centre necrotises, resulting in sharply marginated ulcers with an erythematous halo and a clean-looking floor. The ulcers are covered with layers of crusts resembling oyster shells. The trunk, palms, soles and mucous membranes were reported to be less commonly involved. The liver is the most commonly extra-cutaneous involved organ, particularly in HIV patients.2–6 The diagnosis is based on clinical-histological features and serology.2 Fishers et al.’s7 criteria for diagnosing malignant syphilis are: compatible gross and microscopic morphology; a high titre of positivity for serologic tests for syphilis; Jarisch Herxheimer reaction following treatment and a dramatic response to antibiotic therapy. Historically, it has been argued that lesions due to malignant syphilis can be highly organism depleted and treponemes cannot be detected in all secondary syphilitic lesions.8 However, recently it was demonstrated that an appropriate immunohistochemical study with anti-Treponema antibodies can identify high numbers of the aetiologic agent in a skin biopsy, increasing the diagnostic sensitivity and specificity.9 The guidelines of the Centers for Disease Control and Prevention make no specific recommendation for malignant syphilis, with or without HIV seropositivity.10 The treatment for late latent syphilis is the most frequently used and the outcome is usually good after an early treatment.2,3 Currently, the number of patients reported with malignant syphilis is small, but with the rising incidence of HIV positivity, occurrence of this disease will become more common. Our case is interesting, not only because a very uncommon form of secondary syphilis was identified but also for being diagnosed in an immunocompetent patient. Thus, it is, once more, emphasised the typical polymorphism of this disease always justifying high levels of clinical suspicion. Lack of awareness of this type of presentation delays the diagnosis and treatment, leading to an increase in morbidity and spread of infection.
Conflict of interest The authors declare no conflict of interest.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Wang H, Wang X and Li S. A case of lues maligna in an AIDS patient. Int J STD AIDS 2012; 23: 599–600. 2. Kumar B and Muralidhar S. Malignant syphilis: a review. AIDS Patient Care STDS 1998; 12: 921–925. 3. Garcı´ a-Martı´ nez FJ, Ferna´ndez-Redondo V, Sa´nchezAguilar D, et al. Malignant syphilis in an immunocompetent patient. Actas Dermosifiliogr 2012; 103: 437–439. 4. Tosca A, Stavropoulos PG, Hatziolou E, et al. Malignant syphilis in HIV-infected patients. Int J Dermatol 1990; 29: 575–578. 5. Sands M and Markus A. Lues Maligna, or ulceronodular syphilis, in a man infected with human immunodeficiency virus: case report and review. Clin Infect Dis 1995; 20: 387–390. 6. Malincarne L, Pasticci MB, Angeli G, et al. Syphilis as a diagnosis of liver abnormalities in HIV. Scand J Infect Dis 2013; 45: 703–705. 7. Fisher DA, Chang LW and Tuffanelli DL. Lues maligna. Arch Dermatol 1969; 99: 70–73. 8. Pleimes M, Hartschuh W, Kutzner H, et al. Malignant syphilis with ocular involvement and organism-depleted lesions. Clin Infect Dis 2009; 48: 85–85. 9. De Socio GV, Simonetti S, Tomasini C, et al. Malignant syphilis with ocular involvement in an HIV-infected patient. Int J STD AIDS 2011; 22: 298–300. 10. Workowski KA and Berman S. Centers for disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 2010; 59: 1–110.
Downloaded from std.sagepub.com at Umea University Library on September 5, 2014
Malignant Lues in an immunocompetent patient João Alves, Ana Marta António, Diogo Matos, Ricardo Coelho and Pedro Cachão Int J STD AIDS published online 11 July 2014 DOI: 10.1177/0956462414544162 The online version of this article can be found at: http://std.sagepub.com/content/early/2014/07/11/0956462414544162
Published by: http://www.sagepublications.com
Additional services and information for International Journal of STD & AIDS can be found at: Email Alerts: http://std.sagepub.com/cgi/alerts Subscriptions: http://std.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Jul 11, 2014 What is This?
Downloaded from std.sagepub.com at Umea University Library on September 5, 2014
XML Template (2014) [9.7.2014–12:23pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/STDJ/Vol00000/140136/APPFile/SG-STDJ140136.3d
(STD)
[1–3] [PREPRINTER stage]
Int J STD AIDS OnlineFirst, published on July 11, 2014 as doi:10.1177/0956462414544162
Case report
Malignant Lues in an immunocompetent patient
International Journal of STD & AIDS 0(0) 1–3 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0956462414544162 std.sagepub.com
Joa˜o Alves, Ana Marta Anto´nio, Diogo Matos, Ricardo Coelho and Pedro Cacha˜o
Abstract Malignant Lues is a rare form of secondary syphilis mostly associated with HIV infection. It is an uncommon presentation of syphilis even rarer in immunocompetent patients. We present the case of a 57-year-old homosexual man referred to our department due to a 4-month history of a disseminated, slightly painful, nodular-ulcerative cutaneous eruption associated with low-grade fever, malaise and asthenia. Regarding the clinical features and serological and histopathological findings, the diagnosis of syphilis maligna was assumed. Serology for HIV was repeatedly negative. This case is interesting, not only because a very uncommon form of secondary syphilis was identified but also for being diagnosed in an immunocompetent patient. Lack of awareness of this type of presentation delays the diagnosis and treatment, leading to an increase in morbidity and spread of infection.
Keywords Syphilis (Treponema pallidum), bacterial disease Date received: 18 May 2014; accepted: 23 June 2014
Malignant Lues is a rare form of secondary syphilis mostly associated with HIV infection.1 It is characterised by polymorphous, disseminated, papulonodular cutaneous lesions, typically ulcerated and covered by rupioid crust. Associated systemic findings are common.2 It is an unusual presentation of syphilis even rarer in immunocompetent patients.3 A 57-year-old homosexual man, with no medical history was referred to our department due to a 4-month history of a disseminated, slightly painful, nodularulcerative cutaneous eruption associated with lowgrade fever, malaise and asthenia. The patient reported unprotected sex with one male partner in the last 4 years. The skin examination showed isolated, rounded, well demarcated, erythematous-violaceous, tender nodules and plaques of varying sizes located on head, neck, trunk and limbs, sparing palms, soles and mucous membranes. Some lesions were ulcerated and covered by rupioid brown crusts (Figure 1). There was no lymphadenopathy or palpable hepatosplenomegaly. The neurological examination was normal. The suspected clinical diagnoses included cutaneous lymphoma, syphilis, pyoderma and systemic mycosis. Laboratory analysis showed a slightly elevated erythrocyte sedimentation rate (78 mm/1st hour) with no other
alteration, including liver and kidney function tests. Serologic tests revealed a high titre of RPR (>128) and TPHA (>5120). Serology for HIV, hepatitis B and C were negative. Immunophenotyping of blood lymphocytes was normal, including the CD4 cells count. Immunoglobulins levels were within the normal range. Skin biopsy was performed and revealed a diffuse dermal inflammatory infiltrate composed by plasma cells, histiocytes and lymphocytes, forming granulomas on deeper dermis (Figure 2). These aspects were compatible with a late secondary syphilis. Given the history, clinical examination and histological features, the diagnosis of syphilis maligna was assumed. Having the late symptomatology, severity, rarity and presence of systemic symptoms, the patient was treated with benzathine penicillin 2.4 million units weekly intramuscularly for 3 weeks. An excellent clinical response was observed. After 6 weeks, he was Department of Dermatology and Venereology, Garcia de Orta Hospital, Almada, Portugal Corresponding author: Joa˜o Vı´tor Pina Alves, Department of Dermatology and Venereology, Garcia de Orta Hospital, Av. Torrado da Silva, 2801-951 Almada. Email: [email protected]
Downloaded from std.sagepub.com at Umea University Library on September 5, 2014
XML Template (2014) [9.7.2014–12:23pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/STDJ/Vol00000/140136/APPFile/SG-STDJ140136.3d
(STD)
[1–3] [PREPRINTER stage]
2
International Journal of STD & AIDS 0(0)
Figure 1. Rounded, erythematous-violaceous, nodules and plaques located on neck, trunk and superior limbs. Ulcerations covered by rupioid crust on arms (b and c).
Figure 2. Diffuse dermal inflammatory infiltrate, predominantly perivascular, composed by large numbers of plasma cells, histiocytes and lymphocytes, forming granulomas on deeper dermis (a – hematoxylin and eosin 40; b – hematoxylin and eosin 400).
asymptomatic and had only residual hyperpigmented macules. Three months later, RPR value remained unchanged. At this time, a lumbar puncture was performed which was negative for neurosyphilis. The treponemal IgM test was also negative. Patient has remained on follow-up and 1 year after therapy a 4fold decrease in RPR was observed. HIV was repeatedly negative. Serologic tests performed to his sexual partner diagnosed a latent syphilis. The term ‘malignant’ was used in association with secondary syphilis by Bazin in 1859 and has been used to describe the grotesque clinical findings. People of
poor health, malnourished and alcoholics were commonly affected.2 Currently, most cases have been described in intravenous drug abusers and, mainly, in HIV-infected patients.3 The pathogenesis seems to depend on the host rather than on the causative agent. This is because, as in our case, patients with malignant syphilis have acquired the infection from persons with the routine manifestations of syphilis.2 The incubation period varies from 6 weeks to 1 year following primary infection. Disease onset is characterised by the prodrome of fever, arthralgia, myalgia, headache and photophobia.2 Skin lesions start as
Downloaded from std.sagepub.com at Umea University Library on September 5, 2014
XML Template (2014) [9.7.2014–12:23pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/STDJ/Vol00000/140136/APPFile/SG-STDJ140136.3d
(STD)
[1–3] [PREPRINTER stage]
Alves et al.
3
papules that evolve into nodules and pustules; within a few days the lesion centre necrotises, resulting in sharply marginated ulcers with an erythematous halo and a clean-looking floor. The ulcers are covered with layers of crusts resembling oyster shells. The trunk, palms, soles and mucous membranes were reported to be less commonly involved. The liver is the most commonly extra-cutaneous involved organ, particularly in HIV patients.2–6 The diagnosis is based on clinical-histological features and serology.2 Fishers et al.’s7 criteria for diagnosing malignant syphilis are: compatible gross and microscopic morphology; a high titre of positivity for serologic tests for syphilis; Jarisch Herxheimer reaction following treatment and a dramatic response to antibiotic therapy. Historically, it has been argued that lesions due to malignant syphilis can be highly organism depleted and treponemes cannot be detected in all secondary syphilitic lesions.8 However, recently it was demonstrated that an appropriate immunohistochemical study with anti-Treponema antibodies can identify high numbers of the aetiologic agent in a skin biopsy, increasing the diagnostic sensitivity and specificity.9 The guidelines of the Centers for Disease Control and Prevention make no specific recommendation for malignant syphilis, with or without HIV seropositivity.10 The treatment for late latent syphilis is the most frequently used and the outcome is usually good after an early treatment.2,3 Currently, the number of patients reported with malignant syphilis is small, but with the rising incidence of HIV positivity, occurrence of this disease will become more common. Our case is interesting, not only because a very uncommon form of secondary syphilis was identified but also for being diagnosed in an immunocompetent patient. Thus, it is, once more, emphasised the typical polymorphism of this disease always justifying high levels of clinical suspicion. Lack of awareness of this type of presentation delays the diagnosis and treatment, leading to an increase in morbidity and spread of infection.
Conflict of interest The authors declare no conflict of interest.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Wang H, Wang X and Li S. A case of lues maligna in an AIDS patient. Int J STD AIDS 2012; 23: 599–600. 2. Kumar B and Muralidhar S. Malignant syphilis: a review. AIDS Patient Care STDS 1998; 12: 921–925. 3. Garcı´ a-Martı´ nez FJ, Ferna´ndez-Redondo V, Sa´nchezAguilar D, et al. Malignant syphilis in an immunocompetent patient. Actas Dermosifiliogr 2012; 103: 437–439. 4. Tosca A, Stavropoulos PG, Hatziolou E, et al. Malignant syphilis in HIV-infected patients. Int J Dermatol 1990; 29: 575–578. 5. Sands M and Markus A. Lues Maligna, or ulceronodular syphilis, in a man infected with human immunodeficiency virus: case report and review. Clin Infect Dis 1995; 20: 387–390. 6. Malincarne L, Pasticci MB, Angeli G, et al. Syphilis as a diagnosis of liver abnormalities in HIV. Scand J Infect Dis 2013; 45: 703–705. 7. Fisher DA, Chang LW and Tuffanelli DL. Lues maligna. Arch Dermatol 1969; 99: 70–73. 8. Pleimes M, Hartschuh W, Kutzner H, et al. Malignant syphilis with ocular involvement and organism-depleted lesions. Clin Infect Dis 2009; 48: 85–85. 9. De Socio GV, Simonetti S, Tomasini C, et al. Malignant syphilis with ocular involvement in an HIV-infected patient. Int J STD AIDS 2011; 22: 298–300. 10. Workowski KA and Berman S. Centers for disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 2010; 59: 1–110.
Downloaded from std.sagepub.com at Umea University Library on September 5, 2014
