Medical Mystery of the Week

      You have recieved your COVID19 immunizations but nonetheless are still practicing telemedicine.
      You are shown a picture of the feet of a 33-year-old man who was admitted to the hospital 2 days ago with a chief complaint of fever, chills, arthralgias, malaise, anorexia, and a nonpruitic rash of 2 weeks duration. He has had  "blurry" vision in his right eye of several days duration. You are given no other information about his history.
    His physical examination on admission revealed a temperature of 38.2°C, a blood pressure of 120/75 mm Hg, a regular pulse of 92 beats/minute, and a respiratory rate of 12 breaths/minute. He has a macular rash involving his face, trunk and extremities (see Panel A below). Ophthalmic examination of his right eye is abdormal (Panel B below). His cervical, axillary and inguinal nodes are moderately enlarged and nontender and his abdominal examination reveals hepatosplenomegaly. His joint and neurologic examinations are normal.
     The patient's complete blood count (CBC) shows a mild lymphocytosis with a relative increase in T helper (Th) type17 and Th22 cells. The CBC is otherwise normal. Liver studies reveal an alanine aminotransferase (ALT) of 359 U/L, an aspartate aminotransferase (AST) of 161 U/L, an alkaline phosphatase (ALP) of 580 U/L, and a gamma-glutamyl transpeptidase (GGT) of 883 U/L.  His bilirubin levels are normal. Other laboratory studies, including a chest x-ray and urinalysis, are normal. 
      What is your diagnosis, what test(s) would you order to confirm your suspicions, and what treatment, if any, do you advise?
DIAGNOSIS: Secondary syphilis.
Sometimes referred to as the "Great Imitator", secondary syphilis can involve any organ in the body and should be suspected in any sexually active person with unexplained findings.  Clinical manifestations may include mucous membrane erosions, skin rashes, condyloma latum, lymphadenopathy, arthritis, meningitis, encephalitis, stroke, cranial neuropathies, anterior uveitis, retinitis, glomerulonephritis, hepatitis, splenitis, osteitis/periostitis, and alopecia. In addition to a typical macular rash, the presented case had a retinitis in his right eye and a cholangiolytic hepatitis; on liver biopsy, the bile canaliculi were teaming with treponema. 
      The diagnosis of secondary syphilis can be confirmed by a dark field examination of skin scrapings, noting that these lesions are highly contageous. In all cases of suspected syphilis, the clinician should obtain a specific Treponemal test - the fluorescent treponemal antibody absorbed (FTA-abs) or the T. pallidum passive particle agglutination assay (TP-PA). It is important to recognize that the VDRL and the rapid plasma reagin (RPR) test do not measure antitreponemal antibodies. All patients with secondary syphilis should have a lumbar puncture with examination of the CSF for white blood cells, glucose, and protein, and for VDRL testing. Keep in mind that HIV+ patients may have impaired antibody responses to T. pallidum.
      Both primary and secondary syphilis are treated with 2.4 million units of benzathine penicillin G intramuscularly in a single dose. Persons allergic to penicillin can be treated with doxycycline 100 mg twice daily or tetracycline 500 mg four times daily for 14 days.
      CNS syphilis is treated with 3-4 million units of penicillin G given IV every 4 hours for 10-14 days. Alternatively, patients can be given 2.4 million units of benzathine penicillin G IM every day along with probenecid 500 mg four times daily for 10-14 days. A FTA-abs or TP-PA should be done at 6, 12, 18, and 24 months post treatment to confirm falling titers (anti-treponem titers stay positive for life). Patients with secondary syphilis may develop a Jarisch Herxheimer reaction (fever, rash potentiation, tachycardia, drop in BP) following treatment (this happened to the presented case).

 Panel A. Picture of the patient's rash. The rash in secondary syphilis is generalized, symmetrical, and evolves from a macular to a papular form if left untreated. It is important to recognize that these lesions contain viable treponema and are highly contagious. Always wear gloves when examining the skin of a patient with secondary syphilis

Panel B. A picture of the posterior chamber of the patient's right eye. The patient's visual blurring was due to syphilitic retinitis.

Bonus Question: Why is this patient complaining of difficulty articulating and swallowing?

ANSWER: The patient has a small thyroid gland attached to the base of her tongue (struma lingualis) which has pushed her uvula to her left. The struma may be a secondary thyroid (usual) or the primary thyroid.