Headache, fever, and joint pain accompanied by a facial rash

Mrs. R, 49 years old, initially came to our family-practice clinic for treatment of a frontal headache, fever, sore throat, and general body aches, all of which had persisted for approximately one week. On questioning, the patient noted that she was prone to sinus infections and that this illness felt similar to others she had experienced in the past. Other than a temperature of 101°F, her physical examination was unremarkable. During this visit, we treated Mrs. R empirically for a sinus infection with a three-day course of azithromycin.

Five days later, Mrs. R was seen in the local ER with complaints of “fever as well as chest and upper back pain.” Blood work was performed, and a gallbladder ultrasound was scheduled. Mrs. R was discharged with a diagnosis of abdominal pain, possibly secondary to acute biliary colic. She was told to return to our office the next day so we could go over her lab results and provide further evaluation. In the meantime, she was prescribed propoxyphene and acetaminophen (Darvocet-N 100) for pain.

1. Follow-up visit

When Mrs. R returned the following day, she remarked that her generalized headache had increased in severity. She complained of daily fevers, with temperatures peaking at 101°F-103.7°F in the afternoon and returning to normal by morning. In addition, she had developed a new-onset rash, which she described as “hivelike.” The rash had initially appeared on her legs and gradually worked its way up her body, eventually involving her torso and face. She had tried treating it with OTC diphenhydramine, to no avail. She also mentioned intense left costovertebral angle tenderness and left posterior chest pain.

A follow-up examination was unremarkable. Mrs. R's BP was 160/100 mm Hg; remaining vital signs were normal. The rash was not visible during the exam. A review of Mrs. R's medical history included West Nile virus infection in 2003 in addition to well-controlled depression and hypertension. Her current medications included escitalopram (Lexapro), estrogen (Premarin), hydrochlorothiazide, irbesartan (Avapro), and fexofenadine (Allegra). She had no known drug allergies. Previous surgeries included a hysterectomy and mastoidectomy. Her family history was significant for heart disease, diabetes, rheumatoid arthritis, and hypertension.

Mrs. R worked as a nurse and nursing instructor. However, she could not remember recently caring for any patients with suspicious illnesses. And although she lived with her husband and six children on a farm, she had not had any direct contact with livestock. There was no history of recent travel. Mrs. R reported no unusual environmental exposure or insect bites. She denied use of tobacco, alcohol, or illicit drugs.

2. Lab results

A review of Mrs. R's lab tests revealed an elevated West Nile immunoglobulin (Ig) G, consistent with her past history of infection. Her C-reactive protein was also high at 36.8 mg/L (normal 0-4.9), as were her aspartate aminotransferase at 154 units/L (normal 15-37), alanine aminotransferase 247 units/L (normal 30-65), and alkaline phosphatase 219 units/L (normal 50-136). Mycoplasma pneumoniae IgG and IgM were weakly positive at 219 and 848, respectively (normal 0-200 and 0-770).

All other lab results were normal, including an erythrocyte sedimentation rate and anti-DNA, antinuclear, anti-Smith, antistreptolysin O, and anti-extractable nuclear antigen (anti-ribonucleoprotein) antibodies. A hepatitis panel was negative as were a rapid flu test and assays for mononucleosis, d-dimer, legionella, HIV, and West Nile IgM.

ECG, chest x-ray, gallbladder ultrasound, hepatobiliary scintigraphy, gallbladder ejection fraction, and head as well as upper and lower abdominal CTs were all unremarkable.

Because Mrs. R's M. pneumoniae test was positive, she was placed on a weeklong course of doxycycline 100 mg b.i.d. She was also given hydrocodone and acetaminophen for pain. An infectious disease consult was ordered because of the prolonged fevers of unknown origin.

3. Specialist consult

Ten days after her follow-up visit, Mrs. R presented to the tertiary-care center for evaluation by an infectious disease specialist. In addition to continuing symptoms, Mrs. R had, for the past week, been experiencing joint pain in her hips, elbows, and ribs. There was no joint swelling. Again, an examination and vital signs were unremarkable. 

After reviewing Mrs. R's lengthy records, the specialist considered a diagnosis of limited viral infection, although he noted that Mrs. R's symptoms had lasted longer than would be expected. Additional possibilities included infection with parvovirus B19, because of the prominent joint symptoms, or an acute fungal infection.

Negative serologic studies ruled out the fungal infections, histoplasmosis, cryptococcosis, and blastomycosis. Mrs. R was also tested for parvovirus B19 IgM and IgG antibodies. The IgG was negative at 0.3 (<0.9 = negative), indicating the absence of immunity from past infection. However, the IgM results were positive at 6.2 (>1.1 = positive). Mrs. R was diagnosed with erythema infectiosum (EI), a clinical manifestation of parvovirus B19 infection.

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