Papulonecrotic tuberculid mimicking lues maligna in an immunocompromised male

A case of ocular neurosyphilis in a patient with HIV

Case 1 A 42‐year‐old married man reported heterosexual behavior with multiple partners, chronic alcoholism, and a previous history of urethritis. He presented with a 1‐year history of two asymptomatic, erythematous to violaceous, annular or polycyclic plaques, involving the anterior aspect of the left thigh. The lesions had raised, well‐defined, infiltrated borders, with irregular crusted ulcers at the periphery, and there was central healing with atrophy (Fig. 1). Histologic examination of a skin biopsy specimen showed lymphocytes and plasma cells infiltrating the superficial and deep dermis, and epithelioid granulomas. Warthin–Starry stain for spirochetes was negative. Venereal Disease Research Laboratory (VDRL) test was reactive (1 : 64) and Treponema pallidum hemagglutination assay (TPHA) was positive. Tests for hepatitis B, hepatitis C, human immunodeficiency virus‐1 (HIV‐1), and HIV‐2 were negative. Neurologic examination revealed changes attributable to chronic alcoholism. VDRL test and TPHA of cerebrospinal fluid were negative. Echocardiogram showed moderate dilatation of the ascending aorta, thickening of the aortic valves, and moderate aortic insufficiency. The patient received 2.4 million units of benzathine penicillin G, intramuscularly, once per week for three consecutive weeks, with rapid resolution of the lesions. His wife had a nonreactive VDRL test and positive TPHA, and was treated with the same regimen.Erythematous to violaceous plaque, with crusted and ulcerated border, on the left thighimageCase 2 A 32‐year‐old married woman of rural background and residence presented with a 1‐year history of occasionally pruritic, papulonodular lesions, involving the presternal (Fig. 2) and left eyebrow (Fig. 3) regions, papules in a polycyclic configuration, and clusters of erythematous, infiltrated nodules, some of which showed ulceration with a surface crust. There was central atrophy and noncontractile scarring. Her husband had been treated for primary syphilis approximately 5 years earlier with benzathine penicillin G; however, the wife was not notified and therefore was not treated. Histologic examination of a presternal lesion revealed erosion and acanthosis with irregular papillomatosis of the epidermis, a dense superficial dermal infiltrate of lymphocytes, plasma cells, and epithelioid cells, and granulomas with multinucleated giant cells. Warthin–Starry stain was negative. VDRL test was reactive (1 : 128) and TPHA was positive. Serology for hepatitis B and C and for HIV‐1 and HIV‐2 was negative. VDRL and TPHA analyses of the cerebrospinal fluid were negative. The patient was treated with 2.4 million units of benzathine penicillin G, intramuscularly, once per week for 3 weeks, with rapid resolution of the lesions. One year after treatment, there was slight central, noncontractile atrophy and peripheral hyperpigmentation (Fig. 4).Clustered, infiltrated nodules, with crusted surfaces and central atrophic scarring, in the presternal regionimageInfiltrated nodules with crusted surfaces on the left eyebrowimagePresternal lesions, 1 year after treatmentimageCase 3 Accompanied by a social worker, this single, mentally retarded, indigent 42‐year‐old man presented with a greater than 1‐year history of two fetid, erythematous to violaceous, exudative plaques with ulcerated bases and circinate, ulcerated borders, involving the inner aspects of both thighs (Fig. 5). Histologic examination showed marked pseudoepitheliomatous hyperplasia of the epidermis and marked inflammation of the papillary and reticular dermis, mainly with plasma cells (Fig. 6). Warthin–Starry stain was negative. VDRL test was reactive (1 : 8) and TPHA was positive. Serologic tests for hepatitis B and C and for HIV‐1 and HIV‐2 were negative. Neurologic examination revealed profound memory impairment and abnormal balance. Computed tomography scan of the head and evaluation of the cerebrospinal fluid were unremarkable. The patient was treated with three intramuscular injections of benzathine penicillin G, 2.4 million units, over three consecutive weeks. The lesions responded rapidly to treatment, with evolution to peripheral hyperpigmentation and central, noncontractile atrophy.Ulcerated plaques involving the inner aspect of both thighsimageInflammatory infiltrate with predominance of plasma cells (hematoxylin and eosin, ×1000)image

Presence of genital ulcer disease facilitates human immunodeficiency virus (HIV) transmission and their ­diagnosis is essential for the proper management. Venereal Disease Research Laboratory (VDRL) test is used as a screening test for the diagnosis of syphilis. However, unusual VDRL test results have been reported in HIV-infected persons with syphilis. There are reports showing higher than expected VDRL titers as well as biological false positive in most of the studies. A negative Rapid Plasma Reagin (RPR) test or VDRL test result may not rule out syphilis in patients with HIV infection. For laboratory confirmation of syphilis, one specific Treponemal test, namely, Fluroscent Treponemal Antibody Absorption (FTA-ABS) test or Treponema Pallidum Haemagglutination Assay (TPHA) should be done along with VDRL.<br>In the present study, 88 HIV-seropositive patients with history of high-risk behaviour were screened for syphilis by VDRL test. Out of these 88 cases, 42 (47.7%) patients were positive for TPHA and eight (9.1%) patients were reactive for VDRL in various titers. All the eight patients who were reactive for VDRL test were also positive for TPHA test.<br>Persons with HIV infection acquired through sexual route should be screened for sexually transmitted infections (STIs), and all patients with STIs should be counselled for HIV testing. This will help in proper management of patients having STIs and HIV coinfection.

BackgroundSyphilis laboratory diagnosis, is made through the dosage of circulating antibodies in blood, but is not enough when neurological involvement is suspected.A positive Venereal Disease Research Laboratory test (VDRL) result...

Objective To compare the sensitivity and specificity of venereal disease research laboratory （VDRL） test versus several other laboratory tests in the diagnosis of neurosyphilis. Methods Lumber puncture was conducted to obtain cerebrospinal fluid （CSF） from untreated outpatients with latent syphilis （LS） or serofast outpatients with LS. Then, VDRL test, rapid plasma regain （RPR） test, Treponema pallidum particle agglutination （TPPA） assay, fluorescent treponemal antibody-absorption （FTA-ABS） test and protein quantification were performed on these CSF samples. The sensitivity, specificity, positive predictive value and negative predictive value were compared between VDRL test and four other laboratory tests in the diagnosis of neurosyphilis. Results Totally, 61 cases of latent syphilis were included in this study. The sensitivity, specificity,positive predictive value and negative predictive value were 93.44% （57/61）, 99.32%（293/295）, 96.61%（57/59）, 98.65% （293/297）for CSF-RPR, respectively, 91.80% （56/61）, 82.71% （244/295）, 52.34% （56/107）,97.99 （244/249） for CSF-TPPA, respectively, 93.44% （57/61）, 82.71% （244/295）, 52.78%（57/108）, 98.39%（244/248） for CSF-FTA-ABS, respectively, and 49.18%（30/61）, 97.29% （287/295）, 78.95% （30/38）,90.25% （287/318） for CSF protein quantification, respectively. Conclusions CSF-VDRL cannot be replaced by CSF-RPR, -TPPA, -FTA-ABS, or CSF protein quantification in the diagnosis of neurosyphilis. CSF-RPR shows a high sensitivity and specificity in the diagnosis of neurosyphilis, with an increased diagnostic capability （area under the receiver operating characteristic curve） compared with CSF-TPPA, CSF-FTA-ABS or CSF protein quantification. Key words: Neurosyphilis; Syphilis serodiagnosis; Sensitivity and specificity; Area under curve

후천성 면역 결핍증 환자에서 ì‹ ê²½ë§¤ë ì´ ë°œìƒí• í™•ë¥ ì€ ì •ìƒì¸ì— 비해 높으며, 임상 증상은 다양하게 ë‚˜íƒ€ë‚ ìˆ˜ 있다. 후천성 면역 결핍증을 가진 42세 남자가 급성 뇌경색 형태의 ì‹ ê²½ ë§¤ë ì¦ìƒì„ 보였으며 이에 대해 항 혈소판 치료, í•­ìƒì œ 치료, 항 바이러스 치료를 함께 ì‹œí–‰í•˜ì˜€ê³ , ì„±ê³µì ìœ¼ë¡œ 치료하였기에 증례로 ë³´ê³ í•˜ëŠ” 바이다. 중심 단어: ì‹ ê²½ë§¤ë ; 사람면역 결핍 바이러스; 뇌경색

Case report: A 28-year-old man with no comorbidities was admitted to our institution with a history of sudden holocranial headache, associated with fever, lowered level of consciousness and meningismus with the need for orotracheal intubation. Computed tomography of the brain was normal and the cerebrospinal fluid (CSF) on 05/28/2022 was yellowish, cloudy, glucose 6.0 mg/ dL, protein 752 mg/dL, cells 25,600 mm³ (neutrophils 92%, lymphocytes 5%), red blood cells 258 mm³, CSF Venereal Disease Research Laboratory (VDRL) 1/8, serum VDRL 1/32, treponemal test positive, human immunodeficiency virus (HIV) negative. Ceftriaxone, ampicillin, and acyclovir were empirically started. Pneumococcus was identified in the culture of CSF and blood cultures on admission and the antibiotic regimen was adequate, maintaining only ceftriaxone. Antibiotic therapy lasted 14 days, he was discharged after 16 days of hospitalization, for outpatient follow-up, with no neurological deficits. Control lumbar puncture on 12/23 revealed clear, colorless CSF, glucose 56 mg/dL, total protein 31.8 mg/dL, no cells or red blood cells, cultures negative. Discussion: Streptococcus pneumoniae is the most common cause of meningitis in adults, in older adults and in the current era, neurosyphilis, is most frequently seen in persons with HIV. There are no similar cases described in the literature. Despite the effectiveness of current antibiotics in clearing bacteria from the CSF, bacterial meningitis continues to cause significant morbidity and mortality worldwide. We describe a rare case of an immunocompetent patient with communityacquired pneumococcal meningoencephalitis associated with neurosyphilis treated with ceftriaxone who did not present sequelae or need for retreatment. Conclusion: It´s a rare cause of meningoencephalitis and has significant morbidity and mortality. More studies are needed regarding susceptibility to meningoencephalitis by multiple germs in immunocompetent patients.Case report: A 28-year-old man with no comorbidities was admitted to our institution with a history of sudden holocranial headache, associated with fever, lowered level of consciousness and meningismus with the need for orotracheal intubation. Computed tomography of the brain was normal and the cerebrospinal fluid (CSF) on 05/28/2022 was yellowish, cloudy, glucose 6.0 mg/ dL, protein 752 mg/dL, cells 25,600 mm³ (neutrophils 92%, lymphocytes 5%), red blood cells 258 mm³, CSF Venereal Disease Research Laboratory (VDRL) 1/8, serum VDRL 1/32, treponemal test positive, human immunodeficiency virus (HIV) negative. Ceftriaxone, ampicillin, and acyclovir were empirically started. Pneumococcus was identified in the culture of CSF and blood cultures on admission and the antibiotic regimen was adequate, maintaining only ceftriaxone. Antibiotic therapy lasted 14 days, he was discharged after 16 days of hospitalization, for outpatient follow-up, with no neurological deficits. Control lumbar puncture on 12/23 revealed clear, colorless CSF, glucose 56 mg/dL, total protein 31.8 mg/dL, no cells or red blood cells, cultures negative. Discussion: Streptococcus pneumoniae is the most common cause of meningitis in adults, in older adults and in the current era, neurosyphilis, is most frequently seen in persons with HIV. There are no similar cases described in the literature. Despite the effectiveness of current antibiotics in clearing bacteria from the CSF, bacterial meningitis continues to cause significant morbidity and mortality worldwide. We describe a rare case of an immunocompetent patient with communityacquired pneumococcal meningoencephalitis associated with neurosyphilis treated with ceftriaxone who did not present sequelae or need for retreatment. Conclusion: It´s a rare cause of meningoencephalitis and has significant morbidity and mortality. More studies are needed regarding susceptibility to meningoencephalitis by multiple germs in immunocompetent patients.

Commentary

Infection with the human immunodeficiency virus (HIV) may affect both the natural course of syphilis and the response to treatment. We examined the response to treatment with high-dose penicillin G in HIV-infected patients with symptomatic neurosyphilis. Neurosyphilis was defined by reactivity in serum treponemal tests for syphilis, neurologic manifestations consistent with neurosyphilis, and a positive Venereal Disease Research Laboratory (VDRL) test on cerebrospinal fluid. We identified 11 HIV-infected patients with symptomatic neurosyphilis; 5 had been treated previously for early syphilis with penicillin G benzathine. Patients were treated with 18 million to 24 million units of penicillin G per day administered intravenously for 10 days. Cerebrospinal fluid was examined approximately 6 and 24 weeks after treatment, when the polymerase chain reaction and rabbit inoculation were used to detect Treponema pallidum. In four of the seven patients studied 24 weeks after treatment, the serum titers on rapid plasma reagin (RPR) testing decreased by at least two doubling dilutions, and four patients had reductions in the cerebrospinal fluid titers on VDRL testing or reverted to nonreactive results. In two patients there was no normalization or improvement in serum titers on RPR testing or cerebrospinal fluid titers on VDRL testing, cell counts, or protein concentrations. One patient relapsed with meningovascular syphilis six months after therapy. T. pallidum was detected by the polymerase chain reaction in cerebrospinal fluid from 3 of 10 patients before treatment, but in none of the 10 post-treatment specimens. In patients with early syphilis who are also infected with HIV, therapy with penicillin G benzathine may fail, and neurosyphilis may develop. The regimen of high-dose penicillin recommended for neurosyphilis is not consistently effective in patients infected with HIV.

In a study designed to evaluate the efficacy of penicillin in HIV-infected patients with syphilis and to determine the clinical and laboratory responses after treatment, 13 patients with HIV infection and syphilis were assessed at enrollment and at the last follow-up examination (median time of 21 months). The Venereal Diseases Research Laboratory (VDRL) test, the Treponema pallidum hemaglutination test, and leukocyte counts in cerebrospinal fluid were evaluated both at enrollment and at the last follow-up visit, and the polymerase chain reaction for Treponema pallidum DNA and the rabbit infectivity test were performed on cerebrospinal fluid samples at the last follow-up visit. Primary syphilis was confirmed in four patients, latent syphilis in five, and neurosyphilis in four. After penicillin treatment, all patients were asymptomatic. The serum rapid plasma reagin test became negative in five patients, and titers declined in eight. The VDRL test, Treponema pallidum DNA, and the rabbit infectivity test were negative in all 13 patients. Except for one patient whose serological titer was slow to decline, all patients had good clinical and serological responses to penicillin. In certain settings, factors other than penicillin treatment failure should be considered in HIV-infected patients with suspected relapse of syphilis.

Serology is the mainstay for syphilis diagnosis and treatment monitoring. We investigated serological response to treatment of syphilis according to disease stage and HIV status. A retrospective cohort study of 264 patients with syphilis was conducted, including 90 primary, 133 secondary, 33 latent, and 8 tertiary syphilis cases. Response to treatment as measured by the Venereal Disease Research Laboratory (VDRL) test and a specific IgM (immunoglobulin M) capture enzyme-linked immunosorbent assay (ELISA; Pathozyme-IgM) was assessed by Cox regression analysis. Forty-two percent of primary syphilis patients had a negative VDRL test at their diagnosis. Three months after treatment, 85%-100% of primary syphilis patients had reached the VDRL endpoint, compared with 76%-89% of patients with secondary syphilis and 44%-79% with latent syphilis. In the overall multivariate Cox regression analysis, serological response to treatment was not influenced by human immunodeficiency virus (HIV) infection and reinfection. However, within primary syphilis, HIV patients with a CD4 count of <500 cells/μL had a slower treatment response (P = .012). Compared with primary syphilis, secondary and latent syphilis showed a slower serological response of VDRL (P = .092 and P < .001) and Pathozyme-IgM tests (P < .001 and P = .012). The VDRL should not be recommended as a screening test owing to lack of sensitivity. The syphilis disease stage significantly influences treatment response whereas HIV coinfection only within primary syphilis has an impact. VDRL test titers should decline at least 4-fold within 3-6 months after therapy for primary or secondary syphilis, and within 12-24 months for latent syphilis. IgM ELISA might be a supplement for diagnosis and treatment monitoring.

Sir, Papulonecrotic tuberculid causing penile ulcers is extremely rare.1 Herewith, we report a case of papulonecrotic tuberculide of the penis in a 56-years-old male. A 56-year-old married male patient was referred to our department with multiple asymptomatic non-healing ulcers over the glans penis of one month duration. He was a heterosexual individual and his wife did not have any genital lesions or discharge. The patient denied any history of pre-marital and extra-marital sexual contact. On physical examination, there were multiple, superficial and deep tender ulcers on the glans penis with ragged, irregular margins and floor covered with necrotic yellow slough (Fig. 1). The urethral meatus was hidden by these ulcerative lesions. Rest of the genital examination was normal. There was no inguinal lymphadenopathy. His systemic examination was unremarkable. Fig. 1 Glans penis showing multiple ulcers The hemogram revealed elevated erythrocyte sedimentation rate (50 mm in the first hour). Tuberculin (Mantoux) test was strongly positive (20 mm × 20 mm). Gram stain of the discharge from the ulcers demonstrated pus cells, Gram positive cocci, and Gram negative bacilli and discharge from the ulcers grew Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis. Ziehl Neelsen stain of the pus did not demonstrate any acid-fast bacilli (AFB). Tzanck smear from ulcer was negative for multinucleated giant cells. Urine sediment examination for AFB and urine culture were noncontributory. Radiological and ultrasound evaluation of the genitourinary system was normal. HIV antibodies test and VDRL test were nonreactive. Systemic evaluation for any focus of tuberculosis was unremarkable. Biopsy from the edge of the ulcer (glans penis) revealed ulcerated epidermis. In the deep dermis, by the side of ulceration, there were caseating tuberculous granulomas along with perivascular infiltrate with vessel wall thickening and endothelial cell swelling. Fite stain for AFB was negative. These features were consistent with papulonecrotic tuberculide. AFB culture of biopsy specimen was negative. Repeated courses of antibiotic therapy did not yield desired results; hence, antitubercular therapy was initiated keeping in mind the possibility of papuloneurotic tuberculide of the penis. Four-drug combination therapy of rifampicin, isoniazid, pyrazinamide, and ethambutol was given for initial 2 months followed by combination of rifampicin and isoniazid to complete total 6 months of standard antitubercular therapy. The lesions started responding to therapy in next two weeks and complete healing with residual depressed scars occurred after three months of therapy (Fig. 2). Fig. 2 Healing with residual depressed scars after 3 months of therapy Tuberculosis of the penis is rare, even in third world countries where the prevalence of tuberculosis remains relatively high.1 Till 1999, only 161 cases of penile tuberculosis were reported.2 Understandably, papulonecrotic tuberculide involving the glans penis is even rarer.3,4 Tuberculides are hypersensitivity reactions to Mycobacterium tuberculosis or its products in individuals with good immunity.5 These cases are characterized by positive tuberculin test, evidence of present or past tuberculosis, absence of M. tuberculosis in the skin lesions and response to antitubercular treatment.5 However, a focus of tuberculosis elsewhere in the body may not be demonstrable in majority of the cases with papulonecrotic tuberculide as in our case.2,6 Papulonecrotic tuberculides are characterized by recurrent eruptions of asymptomatic, dusky red papules, which ulcerate and crust, and heal after a few weeks with varioliform scarring.5,7 These occur symmetrically and predominantly on the extensor aspects (legs, knees, elbows, hands and feet) of the extremities. Other areas that may be rarely affected by papulonecrotic tuberculides are the ears, face, buttocks, perniotic areas and penis.5 In Japan, penile tuberculide has been considered a disease entity.4 Thus, it is important to remember tuberculosis as an underlying cause of penile ulcers, more so in countries like India where prevalence of tuberculosis is still high.

There is a lack of large studies appraising the effect of the human immunodeficiency virus (HIV) on the course of syphilis since the advent of highly active antiretroviral therapy (HAART). We aimed to appraise the effect of HIV on clinical and serologic features of syphilis at baseline and during follow-up in the post-HAART era.We designed a retrospective cohort study of consecutive syphilis cases, diagnosed between 2000 and 2007, in an academic venereal disease center. Data were collected using standardized medical forms. Patients were treated according to the European guidelines. Serologic failure was defined as either a 4-fold rise in Venereal Disease Research Laboratory (VDRL) titers 30-400 days posttreatment or a lack of 4-fold drop in VDRL titers at 270-400 days posttreatment.Among 279 syphilis cases with informative baseline clinical and serologic data, HIV infection was significantly associated with men having sex with men, French origin, multiple partners, lesser usage of condom, history of sexually transmitted disease, early syphilis, anal primary chancre, and cutaneous eruption. Median baseline titer from the Treponema pallidum hemagglutination assay (TPHA) was higher in HIV-infected patients (p = 0.02).Among 144 informative syphilis cases, there was a nonsignificant trend for a lower rate of serologic response among HIV-positive patients (91.8% vs. 98.3%, p = 0.14). Serologic failure was significantly associated with a history of previous syphilis (p < 0.05). The median delay to serologic response was similar in HIV-positive (117 d) and in HIV-negative (123 d) patients (p = 0.44).We conclude that for patients under HAART treatment, the effect of HIV on serologic response to syphilis treatment is likely minimal or absent.

Objectives: This study aims to describe the demographic features, clinical profile, Human Immunodeficiency Virus (HIV) status, and visual outcome after completing treatment in patients diagnosed with uveitic syphilis. Methods: A retrospective review was conducted of all cases diagnosed with ocular syphilis from January 2014 to December 2019 at the ophthalmology clinic of Selayang Hospital, Selangor, Malaysia. A total of 31 cases were reviewed, and the collected data included demographic features, history of high-risk behavior, ocular symptoms and signs, visual acuity at presentation and after completing treatment, treatment received, complications, and HIV status. Serology tests to confirm the diagnosis were also included, such as the rapid plasma reagin (RPR), venereal disease research laboratory test (VDRL) titer, and treponema pallidum hemagglutination (TPHA) tests, and some cases also included the VDRL cerebrospinal fluid (CSF) test. Results: A total of 31 patients with ocular syphilis were identified within the study period. Male patients comprised the majority with 27 cases. Nineteen patients were below the age of 50. The majority were ethnic Malay (21 patients). Seventeen patients were identified to have HIV co-infection. Twenty patients reported high-risk behaviors, and among them, six cases were HIV-infected homosexuals. The commonest symptom was blurring of vision (61%), followed by eye redness (16%), floaters (13%), and incidental findings (10%). There were 18 bilateral cases and 13 unilateral cases. The larger share presented as panuveitis (14 cases), followed by intermediate uveitis (nine cases), anterior uveitis (four cases), posterior uveitis (two cases), endophthalmitis (one case), and branch retinal vein occlusion (one case). RPR and TPHA tests were done for all patients. Only 12 patients consented to lumbar puncture for a CSF VDRL test, and one tested positive. All patients received intravenous (IV) administration of 3.0 to 4.0 million units of benzylpenicillin every four hours for 14 days. All cases reported a good outcome with an improvement in visual acuity of at least two Snellen lines after treatment. Conclusion: Early detection and treatment of ocular syphilis will usually preserve visual acuity and ocular function. This study highlights the need for a high degree of suspicion of HIV co-infection, as the majority of our patients were discovered to be HIV-seropositive. Thus, HIV screening is mandatory in all patients presenting with syphilitic uveitis.

Human immunodeficiency virus infection and syphilis among homeless people in a large city of Central-Western Brazil: prevalence, risk factors, human immunodeficiency virus-1 genetic diversity, and drug resistance mutations