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Bits and Pieces
  • Syphilis
  • Syphilis clinical features
  • Syphilis differential diagnosis
  • Syphilis pathology
  • Syphilis diagnostic procedure
  • Syphilis treatment
  • Syphilis references

  • Syphilis

    Syphilis has been a persistent public health challenge for centuries, and is once again the focal point of study because of its co-infection association with HIV. It is a systemic disease caused by the spirochete Treponema pallidum. Spirochetes are slender, spiral, motile bacteria of the order Spirochaetales, most of which are pathogenic. Syphilis is passed from person-to-person through direct contact with a syphilis sore called a chancre. Chancres mainly occur on the external genitals, but may also occur on the lips and in the mouth. If untreated or ignored, the condition can progress to a chronic systemic disease.

    The frequency of syphilis in the general population goes in cycles. During the latter half of the 1980s, the most recent syphilis epidemic peaked throughout the United States. This particular syphilis epidemic was apparently associated with increased crack cocaine use. In 1991, the number of reported cases of primary and secondary syphilis began to decline for the first time since 1985. With a national awareness drive, the number and rate of syphilis cases dropped and the number of cases reported in 1999 were the lowest ever reported in the United States.

    At least four factors may have contributed to the recent decline in syphilis:

    • Increased state and federal programs for syphilis control
    • Implementation of HIV prevention activities
    • Decrease in the use of crack cocaine
    • The presence of acquired immunity in the at-risk population following the epidemic.

    Syphilis typically has three stages – primary, secondary, and late (tertiary), with different symptoms at each stage of the infection. Scalp hair loss does not occur in primary syphilis unless there is a primary lesion (usually an eruption comprising of papules and scales) on the scalp. This imperceptible hair loss can easily be overlooked by the patient, and careful evaluation of hair loss by the experienced clinician is of utmost importance to diagnosis. However, in the secondary and tertiary stages of syphilis, hair loss is common and obvious.

    Syphilis clinical features

    “Moth-eaten” alopecia is the most typical look of secondary syphilis on the scalp. This hair loss in its classic form resembles a somewhat diffuse and patchy alopecia areata (patches of hair loss with ragged edges to the alopecia spots). There may be hair loss from the eyebrows, and a patchy alopecia in the beard and other hair-bearing areas of the body is also common.

    Apart from the recognizable moth-eaten alopecia of secondary stage of syphilis, a less well-known pattern of diffuse hair loss associated with secondary syphilis is called essential syphilitic alopecia. This type of hair loss occurs in the absence of any other cutaneous signs of syphilis and resembles the diffuse hair loss pattern as seen in telogen effluvium.

    A third form of hair loss is associated with the nodulo-ulcerative cutaneous lesions found in patients with lues maligna. Lues maligna is a rare ulcerative form of secondary syphilis characterized by papulopustular skin lesions that rapidly enlarge and evolve into round or oval ulcers with sharp borders, centrally covered by a dark crust. This noduloulcerative or papulopustular presentation of secondary syphilis may affect the scalp as well as other areas of the body. From the histological aspect, this condition is a necrotizing vasculitis and occurs more in patients with HIV infection. When scalp involvement is severe, destruction of the hair follicle with subsequent scarring may occur. There also seems to be a correlation between the papulopustular type and the development of neurosyphilis, which is syphilis that has reached the central nervous system.

    Tertiary or advanced stage of syphilis is characterized by gumma which are small, rubbery granuloma in the skin having a necrotic center and an inflamed, fibrous capsule. In such cases, hair loss occurs in the area overlying the gumma.

    Syphilis differential diagnosis

    The irregular moth-eaten type of alopecia on the scalp seen in secondary syphilis resembles the diffuse pattern of hair loss of patchy alopecia areata. The type of hair loss seen in essential syphilitic alopecia occurs without any cutaneous signs of syphilis and mimics the diffuse hair loss as seen in telogen effluvium.

    Syphilis pathology

    Microscopic examination of an area of patchy or diffuse alopecia in a patient with secondary syphilis reveals an inflammatory, non-scarring alopecia. Follicular changes include a decrease in the percentage of hairs in the anagen (active) phase and a corresponding increase in catagen (transitional stage of hair cycle) and telogen (resting phase of hair cycle) hairs. The infiltrate is described as a sparse, predominantly peribulbar, lymphocytic, superficial perivascular infiltrate with scattered plasma cells and fibrous tract formation.

    In histologic examination of the scalp alopecia of lues maligna, the nodulo-ulcerative form syphilis, the entire dermis shows a perivascular, lymphohistiocytic infiltrate with epithelioid histiocytic granulomata. In the center of the dermis, there is a zone of degenerated collagen and an infiltrate consisting of lymphocytes, histiocytes, neutrophils, and fragmented nuclear particles. This pattern follows vessels that show varying degrees of degeneration and necrosis of vessel walls. Throughout the whole inflammatory reaction, plasma cells are predominant, and the Warthin-Starry stain demonstrates many spirochetes.

    Syphilis diagnostic procedure

    Diagnosis of syphilis begins with a medical history and physical exam. There are two classes of tests used for screening syphilis: treponemal tests and non-treponemal tests.

    • Initial screening for syphilis is performed with one of the non-treponemal antibody tests, the Venereal Disease Research Laboratory (VDRL) test, or the Rapid Plasma Reagin (RPR) test. These tests are very sensitive, but not necessarily specific for syphilis. Treponemal test antibody titers correlate poorly with disease activity and should not be used to assess treatment response. False-positive non-treponemal results can also occur in patients with connective tissue diseases.
    • The specific treponemal tests include the Fluorescent Treponemal Antibody Absorbed (FTA-ABS) and the Microhemagglutination Assay for Antibody to T. pallidum (MHA-TP) tests. Compared with non-treponemal tests, treponemal tests may be positive earlier in the course of infection.

    However, the definitive method to detect T. pallidum is direct visualization of the organism by dark field examinations and direct fluorescent antibody tests of lesion exudates or tissues. The direct fluorescent antibody test has greater specificity and sensitivity than dark field examination.

    Syphilis treatment

    The primary goals of clinicians in syphilis treatment are to avoid disease progression and to prevent transmission. Penicillin as a treatment option has been used in clinical settings for a long time, and remains the cornerstone of syphilis therapy.

    • The standard recommendation for treatment of all stages of syphilis is a weekly intramuscular injection of benzathine penicillin G of 2.4 million units for 1 to 3 weeks. Clinical staging or serological staging (e.g. RPR or VDRL titers) determines the treatment regime.
    • For patients with HIV co-infection, 2.4 million units penicillin G intramuscularly is usually recommended plus anti-retroviral drugs against the HIV.
    • Patients should be informed about the possible adverse reaction called the Jarisch-Herxheimer reaction. This is an acute febrile reaction frequently accompanied by headache and other symptoms that usually occur within the first 24 hours after any therapy for syphilis. This reaction can usually be controlled with corticosteroids or indomethacin.
    • Doxycycline 100 mg orally twice daily or tetracycline 500 mg orally four times a day for 2 weeks is a recommended treatment option for patients who are allergic to penicillin, as an alternative treatment regime.
    • Follow-up cultures or serologic studies should be obtained after completion of therapy. If signs or symptoms persist or recur, or if there is a sustained increase in non-treponemal test titers, the treatment has most likely failed to cure the patient; it may also suggest that the patient has become re-infected and requires re-treatment.

    Syphilis references

    • Nnoruka EN, Ezeoke AC. Evaluation of syphilis in patients with HIV infection in Nigeria. Trop Med Int Health. 2005 Jan;10(1):58-64. PMID: 15655014
    • Abdul Gaffoor PM. Syphilitic alopecia. Indian J Sex Transm Dis. 1990;11(2):66-7. PMID: 12343561
    • Nuttbrock L, Rosenblum A, Magura S, McQuistion HL, Joseph H. The association between cocaine use and HIV/STDs among soup kitchen attendees in New York City. J Acquir Immune Defic Syndr. 2000 Sep 1;25(1):86-91. PMID: 11064509
    • Magura S, Nwakeze PC, Rosenblum A, Joseph H. Substance misuse and related infectious diseases in a soup kitchen population. Subst Use Misuse. 2000 Mar;35(4):551-83. PMID: 10741541
    • Cuozzo DW, Benson PM, Sperling LC, Skelton HG 3rd. Essential syphilitic alopecia revisited. J Am Acad Dermatol. 1995 May;32(5 Pt 2):840-3. PMID: 7722040
    • Jordaan HF, Louw M. The moth-eaten alopecia of secondary syphilis. A histopathological study of 12 patients. Am J Dermatopathol. 1995 Apr;17(2):158-62. PMID: 8600781
    • Pandhi RK, Singh N, Ramam M. Secondary syphilis: a clinicopathologic study. Int J Dermatol. 1995 Apr;34(4):240-3. PMID: 7790137
    • Puavilai S, Charuwichitratana S, Polnikorn N, Sakuntabhai A, Timpatanapong P. Clinical and histopathological features of secondary syphilis. J Med Assoc Thai. 1993 Feb;76(2):85-92. PMID: 8228704
    • Lee JY, Hsu ML. Alopecia syphilitica, a simulator of alopecia areata: histopathology and differential diagnosis. J Cutan Pathol. 1991 Apr;18(2):87-92. PMID: 1856348
    • van der Willigen AH, Peereboom-Wynia JD, van der Hoek JC, Mulder PG, van Joost TH, Stolz E. Hair root studies in patients suffering from primary and secondary syphilis. Acta Derm Venereol. 1987;67(3):250-4. PMID: 2442940
    • Winchell SA, Tschen JA, McGavran MH. Follicular secondary syphilis. Cutis. 1985 Mar;35(3):259-61. PMID: 3979110
    • Chapel TA. The signs and symptoms of secondary syphilis. Sex Transm Dis. 1980 Oct-Dec;7(4):161-4. PMID: 7455863
    • Pareek SS. Syphilitic alopecia and Jarisch-Herxheimer reaction. Br J Vener Dis. 1977 Dec;53(6):389-90. PMID: 606336
    • Jeerapaet P, Ackerman AB. Histologic patterns of secondary syphilis. Arch Dermatol. 1973 Mar;107(3):373-7. PMID: 4348110
    • Ploeg DE, Stagnone JJ. Eyebrow alopecia in secondary syphilis. Arch Dermatol. 1964 Aug;90:172-3. PMID: 14162320
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