My home is my castle

A 42-year-old woman was hospitalized because of a 2-week history of increasing fatigue and a single episode of fever (38.38C) starting a day before admission. She had no cough, pleurisy, abdominal pain, nausea, diarrhea, urinary urgency, rash, arthralgias, night sweats, or weight loss. This young patient suffers from nonspecific symptoms, and therefore I would first consider infection, although the differential is broad. On examination, the patient was alert and oriented. Temperature was 37.28C, blood pressure was 122/70 mm Hg, pulse 120 beats per minute, respiratory rate 18 breaths per minute, and oxygen saturation 99% on ambient air. The oropharynx was erythematous with no exudates or tonsillar enlargement. Nontender enlarged lymph nodes up to 1.5 cm in diameter were palpated bilaterally in the cervical and axillary chains. The spleen was palpable 1 cm below the costal ridge. No other abnormalities were identified. The presence of fever, fatigue, lymphadenopathy, and splenomegaly raised the suspicion of a mononucleosis-like illness such as acute infection due to Epstein–Barr virus (EBV) or cytomegalovirus (CMV). Other infections such as human immunodeficiency virus (HIV), adenovirus, herpes simplex virus, Kikuchi’s disease, Streptococcus pyogenes, syphilis, bartonella, mycobacterias, and toxoplasma should also be considered. White cell count was 5,800 per cubic millimeter with 56% neutrophils, 29% lymphocytes, 13% monocytes, and 2% eosinophils. A few atypical lymphocytes were observed in the blood smear. Hematocrit was 34%, platelet count was 425,000 per cubic millimeter, and erythrocyte sedimentation rate (ESR) was 80 mm after 1 h. Serum levels of creatinine, urea, electrolytes, and liver function tests were normal. Albumin level was 3.2 g/dl (normal 2.2–4 g/dl). Blood, urine, and throat cultures were sterile. Serological tests were positive for EBV IgG and CMV IgG and negative for EBV IgM and CMV IgM. HIV, hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV) antibodies and a rapid plasma reagin test were negative. A chest radiograph was normal. Skin tuberculin test was negative. The results for EBV and CMV were consistent with a past infection. Primary CMV infection generally causes mild pharyngitis and lymphadenopathy and is usually associated with hepatitis, which was not present. Although reactivation of CMV may occur, it happens most commonly in the setting of immunosuppression and is therefore unlikely in this previously healthy female. The patient was born in Russia, immigrated to Israel 12 years ago and has not traveled abroad since then. She was married, has three children, and worked as a nurse assistant. Her medical history included mild asthma, diagnosed during childhood and controlled by inhalations of salmeterol and fluticasone as needed, and mild iron deficiency anemia treated with iron preparations. She takes no other medications, and there is no alcohol, tobacco, or illicit drug abuse, or exposure to raw milk or animals. Eleven months before admission, while working in the hospital, she suffered a needle-stick from an unknown patient. Enzyme-linked immunosorbent assay for HIV antibodies was negative at that time. Although the usual time from HIV exposure to the development of symptoms is 2–4 weeks, incubation periods of up to 10 months have been reported [1]. However, the repeated negative tests rule out this possibility. The patient had no coryza or cough that could have supported an adenovirus infection, showed no characteristic rash of herpes, and the sterile throat culture excluded streptococcus pyogenes infection. She had a monogamous relationship, and there was no history of sexually transmitted disease. The absence of oral and genital chancres and the negative rapid plasma reagin test make secondary syphilis unlikely. The patient was born in Russia, where tuberculosis (TB) is not uncommon. However, lack of a previous TB infection in conjunction with the negative tuberculin skin test and normal chest film makes TB unlikely. In the absence of immunodeficiency and without a history of travel, exposure to improperly cooked meat, or contact with animals, the possibilities of toxoplasmosis and cat scratch disease are not high on the list. Although the fever abated a few days after hospitalization, fatigue, weakness, and malaise continued. In the absence of a febrile disease, the prolonged malaise along with the peripheral lymphadenopathy, hypoalbuminemia, and markedly elevated ESR warrants consideration of a systemic noninfectious disease. Immunologic disorders such as systemic lupus erythematosus (SLE), Sjogren’s syndrome (SS), rheumatoid arthritis (RA), and sarcoidosis, as well as malignancy such as lymphoma, Castleman’s disease (CD) and solid tumors should be considered. Tests for rheumatoid factor (RF), antinuclear antibodies (ANA), and ribonucleoproteins (Ro and LA) antibodies were negative. Levels of complement C3 and C4 and