E-Case # 14-B

Tom Heller, M.D.

September 17-21, 2001

A healthy 32 year old man presented to the clinic on July 9^th with a four day history of severe sore throat, low grade fever with chills, myalgias, mild dry cough and chest tightness.  He felt well before the development of these acute symptoms, and he had no significant past medical illnesses.  He does not smoke cigarettes.  He drinks 6 to 8 beers per week, occasionally more on weekends.  He is gay but checks HIV status every 6 months, was last HIV negative 2 months ago and has not engaged in any risky sexual behavior since then.

FH: father died from viral cardiomyopathy at 67.

Physical exam demonstrates temperature of 100.2, BP-110/66, P-96 O2 sat 98%.

O/P: dry, markedly injected, no pus is seen on tonsils; neck is without adenopathy; lungs are clear; cardiac exam is hyperdynamic with prominent PMI but no lifts, and nl S1 and S2 without gallop or murmur. Abdomen was not examined.

Chest x-ray and EKG were normal.  Rapid strep screen was negative.

Patient was reassured that he had no evidence of viral cardiomyopathy and that this illness was most likely a viral pharyngitis/URI from which he should recover in a few days.  He was advised to drink lots of fluids and to take Acetominophen to control fever and aches.

He returned 8 days later with persistence of low grade fever, sore throat, and new symptoms of overwhelming lethargy/fatigue, anorexia, nausea, and 4 lb. weight loss.  On exam the weight loss was confirmed; temp was 99.7, skin was without rash; eyes were non-icteric; mucus membranes were dry and mouth was noteworthy for a few small cold sore like lesions on the lower lip; throat was again injected without exudates on tonsils; non-tender enlarged lymph nodes were now palpable in the anterior cervical chain bilaterally and in both axillae.  Heart and lung exam were again normal.  Liver was slightly tender to palpation and was perhaps minimally enlarged; spleen was non-palpable.  Strep screen was negative (as was culture). 

Now what would you recommend and do?

The patient was thought to have acute mononucleosis and the following bloodwork was ordered: Mono spot test, CBC with smear, LFTs.  Mono spot test was positive. WBC 2,300 with 1.36 neutrophils, 0.35 bands, 0.46 lymphocytes; Hgb-13.7, Hct-38.9; platelets-66,000. Peripheral smear showed no evidence of hemolysis and approximately 20% of lymphocytes appeared atypical.  No other morphologic abnormalities were noted.  LFTs demonstrated an AST of 62 and an ALT of 46 with normal Alk phos and bilirubin.  Patient was told he had acute mononucleosis, was prescribed Compazine for nausea, told to stay away from alcohol, to call if he were unable to keep fluids down, and to otherwise return in two weeks to make sure he was improving.

He returned a week later, able now to keep food down with the help of Compazine, but feeling no better.  His doctor reviewed the previous history and laboratory findings and ordered a test.  What  test would you order?

1. Coombs test and repeat CBC 

2. Repeat LFTS

3. DIC screen

4. Bone Marrow bx

5. Chest xray

6. lymph node biopsy

7. none of the above

Discuss case before proceeding to the following

Case discussion

It's certainly reasonable to consider a Coombs test as acute mononucleosis can be complicated by a Coombs positive hemolytic anemia, but initial Hgb/Hct and peripheral smear did not suggest this was happening and the doctor did not order this test.  The doctor did incidentally order LFTs as mono certainly can cause a hepatitis and the patient's initial LFTs and his tender liver did suggest that the liver was involved, but this was not THE test the doctor ordered (the repeat LFTs did demonstrate ALT rise to 202 and AST to 58).  Given the low platelet count one might be concerned about a consumption coagulopathy, but there was nothing about the peripheral smear that would suggest this and DIC is not really a complication of mononucleosis so this was not ordered.  Bone marrow biopsy might be entertained given the leukopenia and the thrombocytopenia, but given the rest of the clinical picture, a primary bone marrow process was considered unlikely.  Neither a chest xray nor a lymph node biopsy would be be indicated at this point.   The correct answer is none of the above.

The doctor ordered an HIV viral load.  It came back greater than 75,000.  This is a case of acute HIV infection.  These are the take home points:

1. Getting HIV tested every 6 months is a red flag.  A person sure that s/he is practicing safe sex does not need to be tested.

2. A patient at risk for HIV may not think of his behavior as risky.  Therefore, asking an at risk patient whether he's engaged in recent risky sexual practices may lead to misleading answers.  It is better to ask specific, non-judgmental questions about sexual behavior to define risk.

3. Identifying acute HIV infection and treating it will likely result in a vastly improved prognosis for the patient-immune function and long term survival are likely to be benefited by initial aggressive therapy.  Mechanism for this is that in the initial days of HIV infection, the virus targets the very CD4 cells that are cytotoxic against HIV.  Early treatment preserves these CD4 cells and therefore preserves the host cytotoxic T lymphocyte response against the virus. 

4. Identifying acute HIV infection also can help to stem the spread of the disease as the high viral load during acute infection results in a high degree of infectivity.  Since the patient, like this one, thinks he's HIV negative because a recent HIV antibody test was negative, he may be more likely to act irresponsibly just at a time when he's very infectious.  By identifying and treating acute infection, this may be less likely to happen.

5. People with acute HIV seek medical attention, but too often the diagnosis is not made.

6. Acute HIV infection can look for all the world like acute mononucleosis including a positive heterophile antibody.  If the person falls into a high risk group, check an HIV viral load.  Clinical features that should raise your level of suspicion include the following:  1. leukopenia; 2. lymphopenia; 3. less than 50% atypical lymphocytes on peripheral smear (in mono it's usually greater than 90% and in acute HIV identically atypical lymphocytes can be found but usually in much fewer numbers); 4. shallow, sharply demarcated ulcers on the oral mucosa as well as on the the anus and penis occur with significant frequency in acute HIV and not in mononucleosis.

See the following articles for good descriptions of the condition.  Also Up to Date provides an excellent discussion of the subject.

Kahn,JO, Walker,BD, Acute Human Immunodeficiency Virus Type 1 Infection, NEJM 1998,339,33-45

Schacker,T, Collier,AC,et al, Clinical and Epidemiologic Features of Primary HIV Infection, Annals of Int. Med 1996,125,257-264

Quinn,T, Acute Primary HIV Infection, Grand Rounds at The Johns Hopkins Hospital, JAMA 1997,278,58-62

Finally, if you come across a case of acute HIV, UW is conducting a study of the effects of aggressive treatment on immunologic responses and long term clinical outcomes.  To refer a patient to the study, call Janine Maenza, M.D. at 720-4340.

Lastly, my thanks to my colleagues in Family Practice, Sara Waterman and David Inger, who made me aware of this particular case and whose clinical acumen led to the proper diagnosis and treatment.