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
Thomas, a 20-year-old gay man, presents to a Sexual Health clinic 2 days after developing fever and a skin rash. He has felt generally unwell for about 5 days, and he has had a sore throat, mouth ulcers, headache, and generalized aching in his muscles and joints. He has also noticed swollen glands in his neck. Until now his health has been good, he has had no significant previous illnesses, and he is not receiving prescribed drugs. Thomas does not know to which infections he has been immunized. He is concerned that he might have acquired syphilis because a friend had told him that one of his sexual partners had been treated for this infection about 2 months previously. Thomas thinks that he had only unprotected oral–genital sex with this man about 3 months ago. He has been sexually active for about 3 years and he has had about 25 different sexual partners in that time. In the preceding 3 months he has had sexual contact with five different men. Although he is aware of safer sexual practices, he occasionally has unprotected anal intercourse, particularly when he has consumed considerable quantities of alcohol. Ten days prior to his clinic attendance, he had unprotected receptive anal intercourse with an unknown man whom he had met at a sex club. He regularly uses inhalational nitrites (poppers) during sex, and he occasionally uses “ecstasy.”
Thomas, a 20-year-old gay man, presents to a Sexual Health clinic 2 days after developing fever and a skin rash. He has felt generally unwell for about 5 days, and he has had a sore throat, mouth ulcers, headache, and generalized aching in his muscles and joints. He has also noticed swollen glands in his neck. Until now his health has been good, he has had no significant previous illnesses, and he is not receiving prescribed drugs. Thomas does not know to which infections he has been immunized. He is concerned that he might have acquired syphilis because a friend had told him that one of his sexual partners had been treated for this infection about 2 months previously. Thomas thinks that he had only unprotected oral–genital sex with this man about 3 months ago. He has been sexually active for about 3 years and he has had about 25 different sexual partners in that time. In the preceding 3 months he has had sexual contact with five different men. Although he is aware of safer sexual practices, he occasionally has unprotected anal intercourse, particularly when he has consumed considerable quantities of alcohol. Ten days prior to his clinic attendance, he had unprotected receptive anal intercourse with an unknown man whom he had met at a sex club. He regularly uses inhalational nitrites (poppers) during sex, and he occasionally uses “ecstasy.”
21.1 What Conditions Might Cause These Symptoms?
Sexually transmissible causes of fever, skin rash, and lymphadenopathy are shown in Table 21.1.
Table 21.1.
Sexually transmissible causes of fever, skin rash, and lymphadenopathy.
|
Secondary syphilis Primary HIV infection Infectious mononucleosis Hepatitis B Cytomegalovirus Herpes simplex virus |
Secondary syphilis must be high on the list of differential diagnosis, as he has had sexual contact with a male possibly infected with syphilis. The pre-patent period would be in keeping with a diagnosis of secondary syphilis, and, although Thomas apparently did not have unprotected anal intercourse, oral–genital sex is a well-recognized means of acquisition of Treponema pallidum. The clinical features and diagnosis of secondary syphilis are described further in Case 19.
Unprotected receptive anal intercourse is a high-risk factor for the acquisition of HIV, and this infection must also feature prominently on the list of differential diagnoses. Clinical features of acute HIV infection develop in between 50 and 70% of individuals, the pre-patent period varying from 1 to 6 weeks. In symptomatic patients, there is a rapid onset of fever, malaise, headache, myalgia, sore throat, and swollen lymph glands. Diarrhea may also be a feature, and some patients develop oral, genital, or anal ulceration. A symmetrically distributed non-pruritic macular or maculopapular skin rash may be found on the trunk and limbs, and some affected people show signs of immunodeficiency, for example, oral candidiasis. Neurological features include meningitis, acute encephalitis, and peripheral neuropathy.
In a young patient, infectious mononucleosis, caused by Epstein–Barr virus, can cause the symptoms described here. An erythematous macular or maculopapular rash is a feature in a few patients, but oral ulceration is uncommon.
Acute hepatitis B infection can be associated with fever, lymphadenopathy, and an urticarial skin rash.
In acute cytomegalovirus infection, pharyngitis and prominent lymphadenopathy are less commonly found than in infectious mononucleosis.
Primary herpetic gingivostomatitis can be associated with fever, lymphadenopathy, and erythema multiforme.
Other causes of a glandular fever-like illness include rubella, drug reactions, for example, to phenytoin, streptococcal pharyngitis with erythema multiforme, and acute toxoplasmosis (a skin rash is an unusual feature).
Thomas appears listless. His temperature is 37.8°C, and his pulse rate is 90 per minute. There is a maculopapular rash on the trunk and arms (Fig. 21.1) and three aphthous-like ulcers are noted on the gingival margin; the pharynx is markedly reddened, but exudate is not seen. There is significant but minimally tender enlargement of the anterior and posterior cervical lymph glands. Neither the liver nor the spleen is palpable. There are no clinical signs of meningitis, and a brief neurological examination shows no abnormalities.
Figure 21.1.
Maculopapular rash on trunk.
21.2 Has the Physical Examination Help in the Differential Diagnosis?
In the absence of tender enlargement of the liver, viral hepatitis is unlikely, and the finding of pharyngitis with significant lymphadenopathy is unusual in acute cytomegalovirus infection.
Oral ulceration can be a feature of secondary syphilis and of primary HIV infection.
The results of hematological and biochemical tests undertaken at Thomas's initial clinic attendance are shown in Table 21.2.
Table 21.2.
Results of hematological and biochemical tests.
|
Hematology: |
|
|
Hemoglobin |
146 g/L (130–180 g/L)a |
|
Total leucocyte count |
3.9 × 109/L (4.0–11.0 × 109/L) |
|
Neutrophils |
2.9 × 109/L (2.0–7.5 × 109/L) |
|
Lymphocytes |
0.8 × 109/L (1.5–4.0 × 109/L) |
|
Monocytes |
0.2 × 109/L (0.2–0.8 × 109/L) |
|
Basophils |
0.04 × 109/L (0.05–0.1 × 109/L) |
|
Eosinophils |
0.17 × 109/L (0.04–0.4 × 109/L) |
|
Platelets |
94 × 109/L (150–350 × 109/L) |
|
Blood film |
Normocytic, normochromic erythrocytes. Platelets appear reduced in numbers. No atypical lymphocytes seen. |
|
Monospot test |
Negative |
|
Biochemical tests on serum: |
|
|
Bilirubin |
12 μmol/L (2–17 μmol) |
|
Alanine aminotransferase (ALT) |
62 U/L (10–50 U/L) |
|
Alkaline phosphatase |
116 U/L (40–125 U/L) |
|
Gamma glutamyl transferase |
42 U/L (5–55 U/L) |
|
Albumin |
44 g/L (35–50 g/L) |
aNormal values are shown in parentheses.
21.3 How Would You Interpret These Laboratory Findings?
Lymphopenia and thrombocytopenia, with a minimally elevated serum alanine aminotransferase level are the salient laboratory abnormalities. This is not the hematological picture seen in infectious mononucleosis: there is a lymphocytosis (up to 15 × 109/L), and the majority of cells in the peripheral blood have an atypical morphology. In addition, the Monospot test, a rapid screening test for heterophil antibodies, is positive in more than 85% of cases. In secondary syphilis, the peripheral blood leucocyte count is often normal, although a lymphocytosis may be found.
Leucopenia and lymphopenia, sometimes with the appearance of atypical lymphocytes in the peripheral blood, may be found in acute viral hepatitis. The alanine aminotransferase level, however, would be considerably higher than that found in this case.
The laboratory findings in this case would be consistent with a diagnosis of primary HIV infection. Lymphopenia, thrombocytopenia, and mildly elevated hepatic transaminase are often found in the first week after HIV infection. During the second week, there is a lymphocytosis, secondary to an increase in the number of CD8+ T-cells, and abnormal lymphocytes (CD8+ T-cells) are be found in the peripheral blood. The proportion of abnormal cells, however, is lower than that found in infectious mononucleosis or in acute cytomegalovirus infection.
A sample of serum is tested for HIV using a fourth-generation test that is designed to detect IgG and IgM antibodies and HIV p24 antigen. Serological tests for syphilis (an enzyme immunoassay [see Case 18]), hepatitis B (hepatitis B surface antigen and antibody against hepatitis B core antigen – seeCase 32), rubella, Epstein–Barr virus, cytomegalovirus, and Toxoplasma gondii are undertaken. Thomas is also screened for other sexually transmitted infections as described inCase 4.
The test for HIV is positive, but serology for the other viral infections, syphilis and for T. gondii shows no evidence of recent infection. Neisseria gonorrhoeae is cultured from the rectum, and Chlamydia trachomatis DNA is detected by a nucleic acid amplification assay performed on rectal material.
The fourth-generation tests for HIV that detect antibody and antigen are much more sensitive than previous test systems for the identification of acute HIV infection, and the window period between infection and a positive test result has been considerably reduced. False-negative results may occur, however, and if there is strong clinical suspicion that a patient has acute infection, the test should be repeated and the plasma tested for HIV RNA. A positive result should always be confirmed by submitting a second serum sample (technical errors can occur, for example, through mislabeling of blood tubes). Most laboratories confirm a positive enzyme immunoassay result by immunoblotting (Western blotting).
Although serological tests can be negative in early primary syphilis, a negative result excludes secondary infection.
Unprotected receptive anal intercourse, particularly with ejaculation, is a high risk activity for the acquisition of HIV, and concurrent infection with gonorrhea and chlamydial infection increase that risk significantly. There is no doubt that the prevalence of sexual risk-taking has increased in recent years among men who have sex with men (MSM), as evidenced by the continued transmission of HIV and the increased prevalence of other STIs such as syphilis and gonorrhea among MSM in many industrialized countries. Although risk-taking is often attributed to excess use of alcohol, data from numerous studies have failed to find such an association. The use of inhalational nitrites, however, has been associated with unsafe sexual practices.
The confirmatory tests for HIV are positive. The plasma RNA viral load is >1 × 10 6 per mm 3 . A genotypic resistance assay shows no evidence of viral resistance to any class of antiretroviral agents.
The diagnosis is made. At this stage it is good practice to determine if drug-resistant virus has been acquired. This knowledge will facilitate the future choice of antiretroviral therapy when this is indicated.
Currently the treatment of acute HIV with antiretroviral agents is controversial, and neither this aspect of his management nor his subsequent follow-up will be discussed here.