ARTIGO

INTRODUCTION
Syphilis is a systemic bacterial infection caused by a spirochete, Treponema pallidum of the subspecies pallidum. It’s a chronic disease with an endemic character in developing countries, which occurs with lower frequency in developed countries. It is considered an important problem in individual health and public health because of its associated morbidity and mortality.¹
Historically, a fluctuation in its incidence and prevalence is described, with peaks during World War II and in the late 1980s, having been declining since then,² reaching a minimum value recognized in 20003. The great positive impact in its prevalence was allowed by the treatment with Penicillin, for which there are no reported resistances. Nowadays, its higher prevalence is recognized in groups with sexual risk behaviors, namely men who have sex with men^3,4 and in individuals infected with human immunodeficiency virus (HIV) infection.¹
The natural history of syphilis alternates periods of activity with others of latency. The contagious character of primary and secondary syphilis distinguishes them from tertiary syphilis. Treponema pallidum has an incubation period of 2 to 6 weeks, after which a primary lesion arises at the inoculation site with regional lymphadenopathy usually associated. Secondary syphilis is the most commonly recognized ´clinical syndrome´ resulting from hematogenous dissemination. Although secondary syphilis usually presents as cutaneous-mucosal macular rash and generalized lymphadenopathy, hepatic involvement may also occur, which was first described more than 400 years ago,⁵ but is considered rare.^2,6 Tertiary syphilis appears after a period of years or decades, with multisystemic manifestations.
Serological tests are essential in the diagnosis of syphilis since Treponema pallidum is a microorganism that does not grow in culture¹ and its visualization in microscopy is difficult because of the small difference in density between its body and its wall.⁴ There are two types of diagnostic tests available: the non-treponemal and the treponemal tests. The most widely used non-treponemal tests are the Rapid Plasma Reagin (RPR) and the Venereal Disease Research Laboratory (VDRL). Their titers correlate with the disease activity, though the quantitative value cannot be compared between tests.^1,7 Fluorescent treponemal antibody adsorbed (FTA-ABS) and Treponema pallidum passive particle agglutination (TPPA) assays are often used treponemal tests.² Although historically a non-treponemal test was used as a screening test, followed by a confirmatory treponemal test, in recent years and in low-prevalence populations, it has been cost-effective to use a qualitative treponemal test initially, followed by a non-treponemal assay for confirmation. However, this is not valid for individuals with a history of syphilis or in populations with a relative high prevalence of syphilis, due to the frequent detection of persisting treponemal antibodies.¹
Nowadays, syphilis has become less recognized by clinicians because of the lack of familiarity with the myriad of manifestations of the disease.³ However, prompt diagnosis of this condition is crucial for preventing the development of serious clinical conditions, as acute hepatitis.

CLINICAL CASE
We describe the case of a 27-year-old caucasoid male, observed for constitutional symptoms of non-quantified weight loss, anorexia and asthenia with one month of evolution. He also complained of odynophagia and pruritic cutaneous lesions in both legs and lumbago for the last 5 days. He denied any other symptoms. He had personal history of affective psychosis medicated with Lorazepam 1mg once daily and Risperidone 1mg once daily. Consumption of unusual medication, alcohol or illicit drugs were excluded and there was no history of drug allergies. However, he had high-risk sexual behavior, namely unprotected anal sex with other men. On examination, the patient had an emaciated appearance and his usual outfit was large. He was oriented and cooperative, hemodinamically stable and afebrile. The oropharynx was slightly hyperemic and two ulcerated lesions of small diameter (approximately 0.5 cm) were visible in the mucosa of the lower lip. No other facial or cervical lesions were identified. Several lymph nodes were palpated in the left axilla (with more than 1cm of greater axis), mobile and painless, of elastic consistency, with no other changes in the thoracic examination. Abdominal examination excluded the presence of organomegalies or abdominal masses. Inguinal lymph nodes were palpated bilaterally, with similar features to axillary ones (with 1.6 cm of greater axis). The penis presented a painless ulcerated lesion in the neck and corona of the glans with 0.5 cm of greater axis, with clean base and well defined margins, compatible with a chancre lesion. There were no other associated regional inflammatory signs and no other relevant changes. Inspection of both lower limbs revealed an erythematous, non-desquamative and pruritic macular rash, more pronounced in the anterior face of the legs, with areas of healthy skin between them. There were no deficits nor asymmetries in the neurological examination.
Laboratory tests showed an elevated alkaline phosphatase (ALP) 467 U/L (N 40-150 U/L) and gamma-glutamyl transferase (GGT) 297 U/L (N < 55 U/L) with normal values of total bilirubin (T Brb) and aminotransferases, and a C-reactive protein (CRP) of 1.37 mg/dL (N < 0.5 mg/dL). Chest X-ray and abdominal ultrasonography were unremarkable. Serologies for hepatotropic viruses (hepatitis B virus and hepatitis C virus) and other sexually transmitted diseases were requested (HIV, Treponema pallidum and Chlamydia trachomatis). All the results were negative, except for the screening of syphilis: Rapid Plasma Reagin (RPR) showed a titer of 1:64, which was confirmed by the presence of Immunoglobulins G and M by chemiluminescence immunoassays (CLIA) method. He was submitted to a lumbar puncture, and the cerebrospinal fluid analysis excluded neurosyphilis. Other causes of hepatitis (infectious, autoimmune and neoplastic) were also excluded. Hepatic biopsy was not performed because the clinical suspicion of syphilis was very high. Despite the presence of an ulcerated lesion in the penis, the diagnosis of secondary syphilis was firmed, considering the presence of rash and the active sexual risk behavior, and the patient was treated with intramuscular benzathine penicillin 2.4 million units, once a week, for 3 weeks. The patient experienced the Jarisch-Hermxheimer reaction and presented an excellent clinical and laboratory response to treatment (Table 1).


DISCUSSION
Syphilitic hepatitis is a well-described entity that occurs in about 0.2% of cases of syphilis3, with fewer than 20 cases reported in Medline since 20008. Its most frequent clinical presentation is hepatitis associated with the typical secondary syphilis rash, but there are some cases of fulminant hepatitis requiring liver transplantation.³ The diagnostic criteria are: elevation of liver enzymes; serological evidence of Treponema pallidum infection with clinical evidence of secondary syphilis; recovery of liver enzyme abnormalities following the institution of appropriate antimicrobial therapy; exclusion of other possible causes of liver damage.^2,6,9
Syphilitic hepatitis often presents with a cholestatic pattern characterized by the predominant increase of ALP, as presented in the described case. In some cases, predominance of hepatocellular damage may occur⁵ and this difference may be related to the stage where the disease is identified: hepatocellular lesion is predominant in early syphilis while the cholestatic pattern is more frequent in late syphilis.⁵ Elevation of bilirubin isn’t common² and wasn’t observed in this case. The RPR 1:64 titer was highly suggestive of the disease, and was confirmed by CLIA methodology.¹⁰
Although there is no specific treatment recommended for syphilitic hepatitis, it usually has a good prognosis. Penicillin benzathine remains the drug of choice in these cases and is recommended when the duration of the disease is unknown or at late syphilis with the dose of 2.4 million units in a weekly intramuscular administration for 3 weeks.¹ In our case, this therapeutic regimen was instituted and the patient presented with an excellent clinical and laboratory response, as expected and usually described.^2,3,6 Evaluation of the response to therapy is often made using non-treponemal tests (VDRL or RPR) and this response is considered positive when there is a four-fold decrease in titers in at least 6 months1 as presented in this case. The most significant serological responses are observed in young patients with high titers at serological tests at the time of diagnosis and in those who experience the Jarisch-Hermxheimer reaction (release of treponemic lipoproteins in the blood, which stimulate the production of inflammatory mediators that provoke the onset of fever, myalgias, rash, hypotension and headache),¹ which was identified in our patient.

Quadro I

Laboratory tests at admission and during follow-up

	Reference values	At the emergency department	After 2 doses of Penicillin	6 months after finishing treatment
Hb (g/dl)	13-17.5	14.2	14.7	15.6
Leuk (x 10^3 /Ul)	4-10	7.96	6.14	6.3
Plat (x 10^3 /Ul)	150-400	264	212	176
ALP (U/L)	40-150	467	73	62
GGT (U/L)	<55	297	46	21
TBrb (μmol/L)	<22	13.7	9.0	11.0
AST (UI/L)	15-46	23	18	24
ALT (UI/L)	13-69	35	19	22
CPR (mg/dL)	<0.5	1.37	0.9	0.7
VDRLL/RPR (titer)	-	1:64	-	1:4
IgG/IgM (CLIA)	<0.9	33.5	-	-

ALP – Alkaline phosphatase, ALT – Alanine aminotransferase, AST – Aspartate aminotransferase, CLIA – Chemiluminescent immunoassay, CRP – C-reactive protein, GGT – Gamma-glutamyl transferase, Hb – Hemoglobin, Leuk – Leukocytes, Plat – Platelets, RPR – Rapid plasma reagin, TBrb – Total bilirubin, VDRL –Venereal disease research laboratory

  BIBLIOGRAFIA  

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