Sexually Transmissible Infections in Clinical Practice

19. An African Man with a Skin Rash

Alexander McMillan1, 2  

(1)

Department of Genitourinary Medicine, NHS Lothian, Edinburgh Royal Infirmary, Edinburgh, Uk

(2)

University of Edinburgh, Edinburgh, Uk

Alexander McMillanFormerly, Consultant Physician, part-time Senior Lecturer

Email: a.amcmm@btinternet.com

Abstract

Charles, a 31-year-old post-graduate student from a country in sub-Saharan Africa, attends you, his General Practitioner, with a 6-week history of a slightly itchy skin rash all over his body. He has also noticed some swollen glands in his neck and under his arms. There are no other symptoms and he is not receiving any medication. The only significant illness in the past was malaria when he was a child. He returned to the United Kingdom 1 week ago after having spent 6 months in his native country. You refer him urgently to a dermatologist.

Charles, a 31-year-old post-graduate student from a country in sub-Saharan Africa, attends you, his General Practitioner, with a 6-week history of a slightly itchy skin rash all over his body. He has also noticed some swollen glands in his neck and under his arms. There are no other symptoms and he is not receiving any medication. The only significant illness in the past was malaria when he was a child. He returned to the United Kingdom 1 week ago after having spent 6 months in his native country. You refer him urgently to a dermatologist.

His temperature is 36.4°C. The dermatologist notes a generalized maculopapular scaling rash on the trunk (Fig. 19.1), arms, forearms, thighs, and upper legs. There are no palmar or plantar lesions. The pharynx is reddened but there is no ulceration. Significantly enlarged lymph nodes are palpated in the anterior and posterior triangles of the neck, the axillae, epitrochlear, and inguinal regions. The spleen is enlarged 1 cm below the costal margin but the liver is not enlarged. There are no other abnormal findings; in particular there are no anogenital lesions. Hematological indices and plasma enzyme tests of liver function are within normal limits.

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Figure 19.1.

Maculopapular rash

A number of conditions enter the differential diagnosis of the skin rash (Table 19.1).

Table 19.1.

Differential diagnosis of a maculopapular skin rash

Pityriasis rosea

Secondary syphilis

HIV infection

Infectious mononucleosis

Rubella

Psoriasis

Erythema multiforme

Lichen planus

Pityriasis lichenoides

Drug eruption

Lymphadenopathy in association with a skin rash may be found in pityriasis rosea, secondary syphilis, HIV infection, infectious mononucleosis, and rubella. The duration of the rash argues against the latter two infections, and the normal hematological indices make infectious mononucleosis an unlikely diagnosis.

As the diagnosis is uncertain, a skin biopsy is performed. There is an infiltration of lymphocytes and plasma cells in the superficial and deep dermis, particularly in relation to blood vessels and hair follicles (Fig19.2 ).

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Figure 19.2.

Lymphocytic and plasma cell infiltration of the superficial and deep dermis

The histology is not specific, but the dermatologist considers secondary syphilis as a possible cause and refers the patient to a Genitourinary Medicine physician.

The physician elicits a sexual history (see Case 1). He is married with two young children who live with their mother in Africa. She is 4 months pregnant. His most recent sexual contact with her had been about 1 month previously; he did not use condoms. Three months ago he had had unprotected sexual intercourse with a sex industry worker in a neighboring town. He has had no other sexual partners in the preceding 5 years. He does not recall ulceration of his penis.

With the history and physical findings, secondary syphilis, HIV, or both infections must be high on the list of differential diagnoses. Both conditions may be associated with skin rash and lymphadenopathy. Although the rash of secondary syphilis has been described as being non-itchy, this is not so in many cases. The long pre-patent period between possible exposure to infection and the development of the skin rash is unusual for primary HIV infection, but, of course, is consistent with that of secondary syphilis. Although fever may be a feature of both conditions, its absence does not preclude the diagnoses.

A rapid Venereal Diseases Research Laboratory (VDRL) test on undiluted serum is requested. The result is negative. Does this exclude the diagnosis of secondary syphilis?

No. One of the most serious disadvantages of the cardiolipin antigen tests, of which the VDRL is one, is the occurrence of the prozone phenomenon. This arises because agglutination is inhibited by excess antibody in the serum. The high protein concentration on the cardiolipin particles increases their charge, resulting in their mutual repulsion and preventing linking by antibody molecules. This is reversed by dilution of the serum and hence protein concentration.

The laboratory scientist repeated the VDRL test, using doubling dilutions of the patient’s serum. She also undertook additional serological tests, the results being as shown in Table19.2.

Table 19.2.

Results of serological tests for syphilis at initial attendance

• Screening anti-treponemal enzyme immunoassay (EIA): POSITIVE

• Venereal Disease Research Laboratory (VDRL) test: POSITIVE at a titer of 256

• Treponema pallidum particle agglutination (TPPA) test: POSITIVE at a titer of >5120

• Anti-treponemal IgM EIA: POSITIVE

A fourth-generation HIV antigen/antibody test was negative, and tests for hepatitis B surface antigen and antibody against hepatitis B core antigen were negative. Tests for gonococcal and chlamydial infections (see Case 1) yielded negative results.

These test results confirm the clinical diagnosis of secondary syphilis and exclude HIV infection (the long interval between the presumed episode of risk and the duration of the clinical features preclude a false-negative HIV test). Charles is treated as described in Case 18.

Signs of secondary syphilis appear 7–10 weeks after infection or 6–8 weeks after the appearance of the primary lesion, if noticed.1Lesions of secondary syphilis result from the spread of T. pallidumthroughout the tissues of the body and the immunological reactions of the host. Skin lesions are the most prominent feature of secondary syphilis, but other organs can be affected, including the liver (hepatitis) and the central nervous system (meningitis). Over a period of months the lesions of early syphilis (primary and secondary) heal and the disease becomes latent.

Charles is followed-up 3, 6, and 12 months after completion of treatment. Figure19.3 shows the changes in the serological tests over that time period.

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Figure 19.3.

Changes in the VDRL and TPPA after completion of treatment

Three months after completion of treatment, the anti-treponemal IgM EIA was positive, but this test became negative by 6 months.

As symptoms and signs of early syphilis regress spontaneously, cure of infection cannot be ascertained by resolution of clinical features. Serological tests for syphilis are therefore required to assess efficacy of treatment. Currently, non-treponemal tests such as the Venereal Diseases Research Laboratory (VDRL) or Rapid Plasma Reagin (RPR) tests are used for this purpose. After successful treatment of primary and secondary syphilis the VDRL titer declines four-fold at 3 months and eight-fold by 6 months. This is clearly shown in the present case. After successful treatment of early syphilis, anti-treponemal IgM declines rapidly and uniformly, and indeed was negative by 6 months is this case. Twelve months after treatment of secondary infection, however, the anti-treponemal IgM EIA is still positive in almost one-fifth of patients, even when the criteria for cure based on the non-treponemal tests (VDRL/RPR) are met. This test then does not appear to be satisfactory for determining cure of secondary syphilis.

Footnotes

1

Primary lesions of the uterine cervix, vagina or rectum may go unnoticed by the patient.