A 45-year-old female with no significant past medical history or comorbidities presented to the emergency department with a two-week history of throbbing headaches and temporal swelling. In addition, the patient reported nausea, fatigue, weakness, and subjective low-grade fevers. She denied any recent travel, drug use or exposure to an infectious disease, although she endorsed multiple unprotected sexual encounters. Her physical examination was notable for periauricular, axillary, and inguinal lymphadenopathy. No hepatosplenomegaly, cardiac murmurs, or skin rashes was found on examination. The rest of the physical exam was unremarkable.
CT scan of the head showed multiple cranial bone lytic lesions (Fig. 1A-E). Labs were significant for elevated alkaline phosphatase. Differentials at the time included: multiple myeloma, metastatic or primary malignancy, and endocrine abnormalities. The patient's hemoglobin, hematocrit, white cell count, platelet count, serum calcium, serum phosphorus, parathyroid hormone, and vitamin D levels were all within normal limits. Her renal function was normal with no evidence of proteinuria. Serum protein electrophoresis and free light chain were normal. Patient was evaluated for possible underlying infectious conditions. Sputum culture was negative, oropharyngeal swab and cultures were negative. HIV, hepatitis B and C screening were negative. Chlamydia, Gonorrhea and trichomonas polymerase chain reaction (PCR) screening were negative. Bartonella henselae, Bartonella quintana, Toxoplasma and Francisella tularensis IgG/IgM were negative. In addition, Epstein Barr virus viral capsid antigen (VCA) IgM and Cytomegalovirus PCR were negative. Monospot test was negative. TB screening by Quantiferon gold plus was negative. Due to concern about metastatic cancer, a positron emission tomography (PET) scan was performed that showed increased avidity in the lung (Fig. 1F). Inguinal lymph node biopsy was performed and returned negative for malignancy, and patient was discharged to follow up in outpatient pulmonary medicine clinic for bronchoscopy and an excisional biopsy. Bronchoscopy and fine needle aspiration (FNA) of the mediastinal and hilar lymph nodes were performed and the pathology report returned negative for malignancy.
Patient was subsequently scheduled for further workup with an axillary excisional lymph node biopsy. Pathological examination of the resected sample showed paracortical and interfollicular hyperplasia, which can be seen in dermatopathic lymphadenitis, viral infections, in response to malignancy, or as part of an autoimmune process; however, a morphologically atypical T-cell population was also found. A small CD-10 positive T-cell population was detected on flow cytometry. While this can be seen in angioimmunoblastic T-cell lymphoma, it was noted that there can be significant morphological overlap with reactive paracortical hyperplasia. The sample was nonreactive to EBV antibodies. Overall, the pathological impression was an abnormal reactive process with expansion of the normal population of follicular T-helper cells. Close follow-up and clinical correlation were recommended.
A few weeks later, the patient returned to the emergency department with complaints of worsening headache, body aches, hoarseness, and low-grade fevers. Patient denied any weight loss or night sweats. Repeat PET CT showed a mass at the gastroesophageal junction. EGD (esophagogastroduodenoscopy) showed esophageal ulcers with candida and HSV. Acyclovir and fluconazole were started. During the admission, further work up revealed the patient was positive for syphilis IgG and IgM. Rapid plasma regain (RPR) was reactive at 1:64 titers. Immunohistochemical staining for Treponema was ordered on the previous axillary lymph node biopsy and was found to be positive. Lumbar puncture was performed and was significant for WBC of 23 cells/muL, with 79% of those cells being lymphocytes, protein ~55 mg/dL, and positive CSF VDRL.
As a result, the patient was diagnosed with neurosyphilis and syphilitic osteitis. Notably, the patient was HIV-negative (per ELISA done at admission and repeated at 1 week after admission and at 3 month follow-up) and was found negative for syphilis a year prior during a routine screening test. The patient was treated with a two-week course of IV penicillin G 24 million units and two weeks of benzathine penicillin G given as 2.4 million units weekly. Patient followed up with the infectious disease clinic later and was found to be clinically improving.