A patient presenting with early syphilis and features of general paralysis of insane – An interesting case report in the 21^st century!

Abstract

A 66-year-old unemployed unmarried male with known men sex men activity since the age of 20 years presented with an erythematous well-defined ulcer on the lower lip and multiple discrete papulo-squamous lesions on the palms, soles, and scrotum. The patient was also in dysphoric mood with grandiose ideas with normal higher function. Knee and ankle jerk reflexes were absent and there was impaired tandem walking. Venereal Disease Research Laboratory (VDRL) and treponema pallidum hemagglutination assay were positive. Cerebrospinal fluid-VDRL was positive with grossly elevated proteins and glucose. HIV test was negative. Magnetic resonance imaging scan of the brain was normal. We made a diagnosis of neurosphilis – General paralysis of insane (GPI) with co-existing early syphilis. The patient was started on crystalline penicillin for 14 days after which there was significant improvement in behavior. We are reporting a rare case of GPI with early syphilis.

Introduction

The tertiary stage of syphilis which includes neurosyphilis and cardiovascular syphilis is seldom seen now-a-days. This is because of early diagnosis and treatment. “Happenstance” treatment also contributes to this which is the intake of multiple courses of penicillin group of antibiotics for unrelated conditions which partially or completely cures an undetected syphilitic infection.[1] However, in the context of HIV infection, neurosyphilis is being encountered.[2] The two main components of parenchymatous neurospyhilis are tabes dorsalis (TD) and general paralysis of insane (GPI). GPI may mimic symptoms and signs of brain tumors, chronic alcoholism, senile dementia, and AIDS-Dementia complex.[3] TD may mimic sign and symptoms of neuropathic disorders such as leprosy and syringomyelia. Due to its extreme rarity pertaining to the aforementioned factors, GPI and TD are now diagnosed only if a high index of suspicion is entertained by the dermatologist. We are reporting here an interesting and rare case of GPI with early syphilis in the absence of HIV infection.

Case Report

A 66-year-old unemployed unmarried male presented with skin lesions of 2½ months duration. The lesions were asymptomatic and initially started on the upper lip as an erythematous area followed by raised lesion at the same site. Later, the patient noted raised and scaly lesions on the scrotum, gluteal region, palms and soles, and then trunk. The patient's bystander revealed the he was of late noncooperative and over talkative. The skin lesions were not associated with any constitutional symptoms. The patient gave a history of multiple unprotected men sex men (MSM) activity since the age of 20 years with known and casual male partners. The contacts were peno-oral contact and he was the active partner. The last sexual contact was peno-oral, 2 months ago with a known MSM partner. There was no history of blood transfusion or intravenous drug abuse. There was no history of past psychiatrist illness.

On examination, the patient was thin built. He was hostile and overt talkative. The facies were normal. There was no generalized lymphadenopathy and other general examination findings were noncontributory. On dermatological examination, the patient had a well-defined erythematous plaque with an ulceration of 2 cm × 3 cm on the upper lip extending from the lateral aspect to the midline. The ulcer was nontender, nonbleeding to touch with indurated base, and floor covered by slough and crust [Figure 1]. The ulcer was suggestive of primary chancre. There were multiple discrete well-defined skin colored to hypopigmented papules and plaques with scaling on the palms [Figure 2], anterior abdomen [Figure 3], and scrotum [Figure 4]. These lesions were suggestive of secondary syphilis. The oral cavity, genital mucosa, and eyes were normal. There was no cervical or inguinal lymphadenopathy. The hair and nails were normal. On neurological examination, he was found to be in a dysphoric mood with grandiose ideas. His cognitive functions and speech were normal. A psychiatric evaluation denoted hypomania and hyperactive delirium. Cranial nerve examinations were within the normal limits with normal pupillary reflex. The eyes were reacting to both light and accommodation. There was no sensory deficit on the lower limbs. Pressure and vibration sense were normal. The motor examination revealed an absent ankle and knee jerk and on cerebellar function examination, the tandem walking was found to be impaired, but the Romberg's test was negative. These clinical features were suggestive of GPI. The cardiovascular system was normal, there was no hepato-splenomegaly and bladder function were normal.

Figure 1.

Well-defined erythematous plaque with ulcer and indurated base on upper lip suggestive of primary chancre

Figure 2.

Well-defined scaly plaques on palms suggestive of secondary syphilis

Figure 3.

Papulo-squamous lesions of secondary syphilis on anterior abdomen

Figure 4.

Scaly plaques on scrotum suggestive of secondary syphilis

The patient's blood hemogram, hepatic, renal function, electrolytes, and erythrocyte sedimentation rate were within the normal limits. Dark field examination from the lip ulcer was negative for treponema pallidium. VDRL was reactive 1:32 dilution and treponema pallidum hemagglutination assay (TPHA) positive. His serological tests of HIV, HbsAg, and HCV were negative. A lumbar puncture followed by cerebrospinal fluid (CSF) examination showed VDRL and TPHA to be positive, white blood cell count 20/mm³ (normal <5 cells/mm³), glucose 119 mg/dL (grossly elevated), and protein 110 mg/dL (grossly elevated). A magnetic resonance imaging (MRI) scan of the brain was normal and did not also show any features of senile dementia or space-occupying lesion. We made a final diagnosis of neurosyphilis – GPI with early syphilis-both primary and secondary syphilis. The patient was started on injection crystalline penicillin 40 lakhs units fourth hourly for 14 days as per National AIDS Control Organization (NACO) regime. This high dose regime was sufficient to treat also early syphilis, so we did not give additional treatment for early syphilis. At the end of the therapy, the patient showed considerable improvement in behavior and interaction with others.

Discussion

Our patient gave a history of multiple unprotected MSM activity for many years. He had an ulcer on the upper lip suggestive of primary chancre. He had papules and plaques with scaling suggestive of secondary syphilis. The patient showed features of dysphoric mood, grandiose delusions, hypomania, and hyperactive delirium. Ankle and knee jerk reflexes were absent and cerebellar examination showed impaired tandem walking. Absent tendon reflexes has been described both in GPI and TD, but our patient did not have any other clinical features of TD. Blood VDRL and TPHA were positive, CSF-VDRL and TPHA were positive, and CSF examination showed elevated cells, proteins, and glucose. HIV test was negative ruling out AIDS-dementia complex. The patient was nonalcoholic. Therefore, we made a final diagnosis of GPI with early syphilis including both chancre and secondary syphilis. Hyperactive delirium has been described in cases of GPI.[4] The MRI scan in our patient was normal. Only in very late cases of GPI, the classical finding of cerebral atrophy and ventricular dilatation is seen in MRI- or computed tomography-scan.[5] The MRI scan and clinical features were discussed with the neurologist and the psychiatrist who concurred with our findings. Our patient also did not show any signs of senile dementia or space occupying lesion in the MRI scan, thus the abnormal behavioral changes can only be attributed to GPI. He also showed significant improvement in behavior after the full course of crystalline penicillin. Hyporeflexia can occur both in GPI and TD. However, our patient did not have any clinical features of TD. Encountering a case of GPI in this 21^st century is the unique highlight of this case. Misdiagnosis is possible if a high index of suspicion is not maintained as all the classical clinical features of GPI may not manifest in the present day due to the frequent use of penicillin group of antibiotics which contribute to “happenstance” treatment. Our patient gave a history of frequent intake of antibiotics (nature not known) for respiratory infections which may have contributed to happenstance treatment. Another interesting feature in our case is the concomitant occurrence of chancre and secondary syphilis lesions. However, this can be explained in the context of the multiple contacts our patient had. The occurrence of early syphilis along with neurospyhilis is described in HIV/AIDS patients, but our patient was HIV negative.[6] In the present era the sign and symptoms of GPI may mimic senile dementia, chronic alcoholism and psychiatric illness. Consequently the physicians may put the patient on anti-psychiatric medications, while the vital drug penicillin is withheld. Reporting of GPI in recent Indian literature (last 20 years) is very rare. However there have been reports of TD with ocular changes.[7] At the same time cases of cardiovascular syphilis have been described in recent times more than neurosyphilis.[8] This could be due to the serious clinical symptoms and signs of cardiovascular syphilis which prompts the patient to seek early treatment. Moreover there is a greater chance of detecting cardiovascular syphilis during routine clinical examination for hypertension, chest pain, palpitations, than for a CNS work up. More often during an angiogram work up VDRL and TPHA is done routinely and latent or cardiovascular syphilis is picked up. The definite treatment for neurospyhilis is crystalline penicillin (Penicillin G) in the above quoted dose which is NACO, Centers for Disease Control and Prevention (CDC), and World Health Organization recommended.[9] This is due to the fact that crystalline penicillin is the only penicillin that crosses the blood–brain barrier (BBB) in adequate amounts to kill treponema pallidium, compared to benzathine and procaine penicillin. There is also a recommendation by CDC for injection ceftriaxone for neurospyphilis in cases of allergy to penicillin in a dose of 1–2 g daily for 10–14 days, as studies have shown that ceftriaxone can cross the BBB and in most cases do not show cross reaction with penicillin.[10] Jarisch–Herxheimer reaction in GPI may manifest as acute maniac episodes and seizures; however, this was not seen in our patient. In the present context, any patient who has high risk sexual behavior and presenting with a STI and cognitive neurological signs and symptoms, the first diagnosis would be AIDS-dementia complex. However, as this case report shows never forget GPI! We are reporting a very rare and interesting case report – GPI in the 21^st century!

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.