INTERNAL MEDICINE BOARDS - PART 7 pot

INFECTIOUS DISEASES 434 FEVER OF UNKNOWN ORIGIN (FUO) Classically defined as a temperature > 38.3°C that lasts at least three weeks and remains undiagnosed despite evaluation for more than two outpatient visits or three hospital days. Etiologies vary depending on the patient’s age, immune status, and geographic location. In the United States, infection (33%), cancer (25%), and, to a lesser extent, autoimmune diseases (13%) are responsible for most identified cases. Infection is likely if the patient is older or from a developing country, as well as in the setting of nosocomial, neu- tropenic, or HIV-associated FUO. Etiologies are as follows: ■ Infectious: TB, endocarditis, and occult abscesses are the most common infectious causes of FUO in immunocompetent patients. Consider 1° HIV infection or opportunistic infections due to unrecognized HIV. ■ Neoplastic: Lymphoma and leukemia are the most common cancers causing FUO. Other causes include hepatoma, renal cell carcinoma, and atrial myxoma. ■ Autoimmune: Adult Still’s disease, SLE, cryoglobulinemia, polyarteritis nodosa, giant cell (temporal) arteritis/polymyalgia rheumatica (more com- mon in the elderly). ■ Miscellaneous: Other causes of FUO include drug fever, hyperthyroidism or thyroiditis, Crohn’s disease, Whipple’s disease, familial Mediterranean fever, recurrent pulmonary embolism, retroperitoneal hematoma, and fac- titious fever. ■ In roughly 10–15% of cases, the cause is not diagnosed. Most of these cases resolve spontaneously. EXAM Repeated physical exams may yield subtle findings in the fundi, conjunctivae, sinuses, temporal arteries, and lymph nodes. Heart murmurs, splenomegaly, and perirectal or prostatic fluctuance/tenderness should be assessed. DIAGNOSIS ■ History: Ask about immune status, cardiac valve disorders, drug use, travel, TB exposure history, exposure to animals and insects, occupational history, all medications (prescription, over-the-counter, and herbals), sick contacts, and family history of fever. ■ Labs/imaging: ■ Obtain routine labs, blood cultures (off antibiotics; hold culture bottles for two weeks), CXR, and PPD. If indicated, obtain cultures of other body fluids (sputum, urine, stool, CSF) as well as a blood smear (malaria, babesiosis) and an HIV test. ■ Echocardiography for vegetations; CT/MRI if neoplasms or abscesses are suspected. ■ Use more specific tests selectively (ANA, RF, viral cultures, antibody/anti- gen tests for viral and fungal infections). ■ Invasive procedures are generally low yield except for temporal artery biopsy in the elderly, liver biopsy in patients with LFT abnormalities, and bone marrow biopsy for HIV. TREATMENT ■ If there are no other symptoms, treatment may be deferred until a defini- tive diagnosis is made. ■ Broad-spectrum antibiotics if the patient is severely ill or neutropenic. FUO is most commonly due to unusual presentations of common diseases rather than to rare diseases. INFECTIOUS DISEASES FOOD-BORNE ILLNESS Table 11.4 outlines the causes and treatment of food-borne illness, grouped according to incubation period. FUNGAL INFECTIONS See Figure 11.2 for typical forms of fungi that might be seen in tissues exam- ined by histopathology. Common fungal infections are discussed below. Candidiasis The opportunistic yeast Candida is a commensal found on the skin, GI tract, and female genital tract. Superficial infection is especially common among diabetics. Risk factors for deep or disseminated infection include immune compromise (HIV, malignancy, neutropenia, or steroids), multiple or pro- longed antibiotic treatment, and invasive procedures. C. albicans is the most common cause. SYMPTOMS/EXAM/DIAGNOSIS ■ Candiduria: Yeast in urine usually represents colonization and not infec- tion. Seen in patients with Foley catheters or antibiotic use. Diagnose in- fection by detecting pyuria or yeast in urine casts; treat if the patient is symptomatic or neutropenic, has undergone renal transplant, or is await- ing urinary tract procedures. ■ Intertrigo (“diaper rash”): Pruritic vesiculopustules rupture to form mac- erated or fissured beefy-red areas at skin folds. Satellite lesions may be pre- sent. Seen in both immunocompetent and immunosuppressed patients. ■ Oral thrush: Presents with burning sensations of the tongue or mucosa with white, curdlike patches that can be scraped away to reveal a raw surface. Seen in patients with AIDS or malignancy or in those who use in- haled steroids for asthma. Diagnosis can be confirmed with KOH prep or Gram stain. ■ Candidal esophagitis: Presents with dysphagia, odynophagia, and subster- nal chest pain. Seen in patients with AIDS, leukemia, and lymphoma. Di- agnosed by the endoscopic appearance of white patches or from biopsy showing mucosal invasion. May occur concurrently with HSV or CMV esophagitis. ■ Candidemia and disseminated candidiasis: Diagnose through cultures of blood, body fluids, or aspirates. Mortality is 40%. Candidemia may lead to endophthalmitis (eye pain, blurred vision), osteomyelitis, arthritis, or en- docarditis. ■ Hepatosplenic candidiasis: Presents with fever and abdominal pain that emerge as neutropenia resolves following bone marrow transplant. Associ- ated with a high mortality rate. Diagnosed by ultrasound or CT imaging showing abscesses. Blood cultures are frequently ᮎ. TREATMENT ■ Candiduria: Most cases do not need treatment. ■ Intertrigo and oral thrush: May be treated with topical antifungals (ny- statin, clotrimazole or miconazole creams, or nystatin suspension swish and swallow). Patients are usually afebrile in toxin-mediated food-borne illness. 435 All patients with candidemia should have an ophthalmologic exam to rule out candidal endophthalmitis. INFECTIOUS DISEASES 436 TABLE 11.4. Causes of Food-Borne Illness DISEASE/ASSOCIATIONS AGENT SYMPTOMS TREATMENT Incubation period < 2 hours: likely toxin or chemical agent Ciguatera (grouper, Neurotoxin from algae Perioral paresthesias and shooting pains in Emetics/lavage snapper) that grow in tropical the legs (may persist for months); within three hours; reefs. bradycardia/hypotension if severe. IV fluids; atropine/pressors, mannitol. Scombroid (tuna, mahi- Histamine-like substance Burning mouth/metallic taste; flushing, Antihistamines. mahi, mackerel) in spoiled fish. dizziness, headache, GI symptoms; urticaria/bronchospasm if severe. MSG poisoning (“Chinese Acetylcholine. Burning sensation in the neck/chest/ No treatment. restaurant syndrome”) abdomen/extremities; sweating, bronchospasm, tachycardia. Incubation period 2–14 hours: likely toxin S. aureus (dairy, eggs, Preformed heat-stable Vomiting, epigastric pain. No treatment. mayonnaise, meat products) enterotoxin. Bacillus cereus Preformed toxin (like Vomiting, epigastric pain, diarrhea. No treatment. S. aureus) or sporulation and toxin production in vivo (like C. perfringens). Clostridium perfringens Toxin is released after Lower GI symptoms. No treatment. (frequently from reheated heat-resistant clostridial meats, stews, gravies) spores germinate in the intestines. Incubation period > 14 hours: bacteria, viruses Campylobacter (most Fever, diarrhea. Ciprofloxacin or common) azithromycin. Salmonella Same as above. Same as above. Shigella Shiga toxin. Same as above. Same as above. Enteroinvasive E. coli Same as above. Same as above. Yersinia Same as above. TMP-SMX or ciprofloxacin. Vibrio parahaemolyticus Same as above. No treatment. (undercooked seafood) INFECTIOUS DISEASES ■ Esophagitis and other deep or disseminated infections: Systemic therapy with fluconazole, amphotericin, voriconazole, or caspofungin. ■ Replace vascular catheters at a new site (do not exchange over a wire!). ■ C. albicans is usually susceptible to fluconazole and can be distinguished from other etiologic agents within several hours by a ᮍ germ tube test (i.e., the yeast grows a germ tube or pseudohyphae). Patients who have been on fluconazole prophylaxis may have resistant C. albicans or non- albicans species (e.g., C. glabrata, C. krusei). COMPLICATIONS Patients with persistent candidemia after catheter removal may have periph- eral septic thrombophlebitis or septic thrombosis of the central veins. Aspergillosis Aspergillus fumigatus and other species are widespread in soil, water, compost, potted plants, ventilation ducts, and marijuana. SYMPTOMS/EXAM ■ Allergic bronchopulmonary aspergillosis (ABPA): Presents with episodic bronchospasm, fever, and brown-flecked sputum. Seen in patients with underlying asthma or CF. CXR shows patchy, fleeting infiltrates and lobar consolidation or atelectasis. Labs show eosinophilia, elevated serum IgE, and ᮍ serum IgG precipitins. ■ Aspergilloma of the lungs or sinus: May be asymptomatic or present with hemoptysis, chronic cough, weight loss, and fatigue. Seen in patients with previous TB, sarcoidosis, emphysema, or PCP. CXR and CT may show an air-crescent sign or a rim of air around a fungus ball in a preexisting upper lobe cavity. Labs show ᮍ serum IgG precipitins. ■ Invasive aspergillosis: ■ Presents with dry cough, pleuritic chest pain, and persistent fever with a new infiltrate or nodule despite broad-spectrum antibiotics. Seen in patients with prolonged neutropenia, advanced AIDS, diabetes, and chronic granulomatous disease as well as in those on high-dose steroids or immunosuppressants. TABLE 11.4. Causes of Food-Borne Illness (continued) DISEASE/ASSOCIATIONS AGENT SYMPTOMS TREATMENT Enterohemorrhagic E. coli Shiga toxin. Usually afebrile; bloody diarrhea; HUS in No antibiotics (may O157:H7 (undercooked 5% of cases. ↑ risk of HUS). ground beef, contaminated produce) Enterotoxigenic E. coli Enterotoxins. Usually afebrile; diarrhea. Ciprofloxacin. (“traveler’s diarrhea”) Norwalk-like virus (cruise Usually afebrile; vomiting, headaches, No treatment. ship outbreaks) diarrhea. 437 INFECTIOUS DISEASES 438 ■ Imaging: CXR and CT may show wedge-shaped lesions from tissue in- farction, an air-crescent sign from cavitation of a necrotic nodule, or a halo sign of a necrotic nodule with surrounding hemorrhage. ■ Labs: The Aspergillus galactomannan assay is approved for diagnosis in patients with hematologic malignancies and following bone marrow transplant. IgG precipitins and blood cultures are rarely ᮍ. In high-risk patients, ᮍ sputum or bronchial washing cultures are strongly sugges- tive, but definitive diagnosis requires a biopsy demonstrating tissue in- vasion. ■ Patients are often severely ill, and empiric antifungal therapy may be reasonable in high-risk patients. DIFFERENTIAL ■ ABPA: TB, CF, lung cancer, eosinophilic pneumonia, bronchiectasis. ■ Aspergilloma: Invasive aspergillosis. FIGURE 11.2. Characteristic forms of fungi in human tissue (37°C). (Reproduced, with permission, from Bhushan V, Le T. First Aid for the USMLE Step 1: 2005. New York: McGraw-Hill, 2005: 191.) Candida albicans Aspergillus fumigatus Endemic mycoses: Cryptococcus neoformans Blastomyces dermatitidi s Paracoccidioides brasiliensis Histoplasma capsulatum Coccidioides immitis INFECTIOUS DISEASES 439 ■ Invasive aspergillosis: Aspergilloma, cavitating lung tumor, nosocomial Legionella infection. TREATMENT ■ ABPA: Systemic corticosteroids plus itraconazole × 8 months improves lung function and ↓ steroid requirements. ■ Aspergilloma: Surgical excision for massive hemoptysis. Antifungals play a limited role. ■ Invasive aspergillosis: Voriconazole, amphotericin, or caspofungin. COMPLICATIONS ■ ABPA: Bronchiectasis, pulmonary fibrosis. ■ Aspergilloma: Massive hemoptysis; contiguous spread to the pleura or ver- tebrae. ■ Invasive aspergillosis: High mortality, especially in bone marrow and liver transplant patients. Cryptococcosis Cryptococcus neoformans is an encapsulated budding yeast found worldwide in soil, bird (pigeon) droppings, and eucalyptus trees. Risk factors for the dis- ease are HIV-related immunosuppression, Hodgkin’s disease, leukemia, and steroid use. C. neoformans is the most common fungal infection in AIDS pa- tients (usually associated with a CD4 count < 100) and is the most common cause of fungal meningitis in all patients. SYMPTOMS/EXAM ■ Meningitis: Mental status changes, headache, nausea, cranial nerve palsies. HIV patients usually lack obvious meningeal signs. ■ May also cause atypical pneumonia (pulmonary infection is usually asymptomatic) or skin lesions (umbilicated papules resembling mollus- cum contagiosum), or may involve the bone, eye, or GU tract. DIFFERENTIAL Meningitis due to TB, neurosyphilis, toxoplasmosis, coccidioidomycosis, histoplasmosis, HSV encephalitis, meningeal metastases. DIAGNOSIS ■ LP: Patients often have high opening pressure, low glucose, high protein, and lymphocytic pleocytosis. Patients with more advanced immunosup- pression may have a bland CSF profile even with meningitis. India ink or Gram stain of CSF may show budding yeast with a thick capsule (both are < 50% sensitive). ■ Polysaccharide cryptococcal antigen (CrAg) in serum or CSF: Serum CrAg is > 99% sensitive in AIDS patients with meningitis but is less sensi- tive in non-AIDS patients. CSF CrAg is only 90% sensitive. A serum CrAg titer of > 1:8 indicates active disease. ■ Fungal culture of blood, CSF, urine, sputum, or bronchoalveolar lavage. ■ CT or MRI may show hydrocephalus or occasionally nodules (cryptococ- comas). Cryptococcemia (a ᮍ serum CrAg or blood culture) indicates disseminated disease even with a normal LP. Unlike what is typically seen in bacterial meningitis, HIV patients with cryptococcal meningitis often have minimal symptoms and a bland CSF. INFECTIOUS DISEASES 440 T REATMENT ■ HIV-ᮎ patients: For mild to moderate lung disease, treat with oral flucona- zole × 6–12 months. For meningitis, cryptococcemia, or severe lung dis- ease, treat with amphotericin plus 5-flucytosine × 2 weeks followed by oral fluconazole 400 mg/day for at least 10 weeks. ■ HIV-ᮍ patients: ■ For mild to moderate lung disease, treat with fluconazole 200–400 mg/day. ■ For severe lung disease, treat with amphotericin until symptoms are controlled followed by fluconazole. ■ For meningitis, give induction/consolidation therapy with ampho- tericin plus 5-flucytosine × 2 weeks followed by oral fluconazole 400 mg/day × 10 weeks. ■ Patients with HIV need long-term maintenance therapy with oral flu- conazole 200 mg/day. It may be reasonable to stop prophylaxis if the CD4 count ↑ to > 100–200 for > 6 months in response to antiretrovirals. ■ Repeat LP until symptoms resolve in patients with coma or other signs of elevated ICP. COMPLICATIONS A poorer prognosis for meningitis is seen in patients with abnormal mental status, those > 60 years of age, and those with evidence of high organism load or lack of immune response (as indicated by cryptococcemia, high initial CrAg titer in CSF or serum, high CSF opening pressure, < 20 WBCs in CSF, low glucose, and ᮍ India ink). Coccidioidomycosis Coccidioides immitis is found in the arid southwestern United States, central California, northern Mexico, and Central and South America. It is found in soil, and outbreaks occur after earthquakes or dust storms. Risk factors include exposure to soil and the outdoors (construction workers, archaeologists, farm- ers). SYMPTOMS/EXAM ■ 1° infection (“valley fever,” “desert rheumatism”): Usually presents with self-limited flulike symptoms, fever, dry cough, pleuritic chest pain, and headache, often accompanied by arthralgias, erythema nodosum, or ery- thema multiforme. CXR may be normal or may show unilateral infil- trates, nodules, or thin-walled cavities. Some patients (5%) may develop chronic pneumonia, ARDS, or persistent lung nodules. ■ Disseminated disease (1%): Chronic meningitis, skin lesions (papules, pustules, warty plaques), osteomyelitis, or arthritis. DIFFERENTIAL Atypical pneumonia, TB, sarcoidosis, histoplasmosis, blastomycosis. DIAGNOSIS ■ Serologic tests (complement fixation assays); titers ≥ 1:32 indicate more severe disease and a higher risk of dissemination. ■ Histology may show giant spherules in infected tissues. Serum CrAg titers are not useful for monitoring treatment response of meningitis in immunosuppressed patients. CSF CrAg titers should ↓ during successful treatment. INFECTIOUS DISEASES 441 ■ Cultures of respiratory secretions or aspirates of bone and skin lesions may grow the organism (alert the laboratory if the diagnosis is suspected; Coc- cidioides is highly infectious to lab workers). TREATMENT ■ Treatment may not be necessary for acute disease but may be reasonable in patients at risk for dissemination. ■ Fluconazole, itraconazole, or amphotericin for disseminated disease. COMPLICATIONS Disseminated disease is more common in nonwhites, pregnant women, and patients with HIV, diabetes, or immunosuppression. Histoplasmosis Histoplasma capsulatum is found in the Mississippi and Ohio River valleys. The organism is found in moist soil and in bat and bird droppings. Risk fac- tors include exploring caves and cleaning chicken coops or attics. SYMPTOMS/EXAM ■ 1° infection: Most patients are asymptomatic. However, patients may present with fever, dry cough, and substernal chest discomfort. CXR may show patchy infiltrates that become nodular or exhibit multiple small nod- ules and hilar or mediastinal adenopathy. Some patients may develop chronic upper lobe cavitary pneumonia or mediastinal fibrosis (dysphagia, SVC syndrome, or airway obstruction). ■ Disseminated disease: Presents with hepatosplenomegaly, adenopathy, painless palatal ulcers, meningitis, and pancytopenia from bone marrow infiltration. Patients with HIV may develop colonic disease (diarrhea, per- foration or obstruction from mass lesions). DIFFERENTIAL Atypical pneumonia, influenza, coccidioidomycosis, blastomycosis, TB, sar- coidosis, lymphoma. DIAGNOSIS ■ Urinary antigen test is most useful in HIV/AIDS patents with dissemi- nated disease. ■ Histology with silver stain of bone marrow, lymph node, or liver. ■ Cultures of blood or bone marrow are ᮍ in immunosuppressed patients with disseminated disease. ■ Serologic tests (complement fixation and immunodiffusion assays) are of- ten ᮍ in immunocompetent patients. TREATMENT ■ Treatment is not needed for acute pulmonary disease. ■ Itraconazole or amphotericin for chronic cavitary pneumonia, mediastinal fibrosis, or disseminated histoplasmosis. COMPLICATIONS Severe or disseminated disease is more common in patients infected with a large inoculum and in elderly, immunosuppressed, and HIV patients. INFECTIOUS DISEASES 442 Blastomycosis Blastomyces dermatitidis is found in the central United States (as is Histo- plasma) as well as in the upper Midwest and Great Lakes regions. Risk factors include exposure to woods and streams. SYMPTOMS/EXAM Acute pneumonia. May lead to warty, crusted, or ulcerated skin lesions or to osteomyelitis, epididymitis, or prostatitis. DIAGNOSIS Microscopy and culture of respiratory secretions; biopsy or aspirate material shows large yeast with broad-based budding. TREATMENT Itraconazole or amphotericin for all infected patients. GUILLAIN-BARRÉ SYNDROME Acute symmetric ascending weakness or paralysis with areflexia; paresthesias may also be present distally. Usually occurs within 30 days of a respiratory or GI infection, especially Campylobacter enteritis, CMV, EBV, or mycoplasmal infection. Differential diagnosis includes the following: ■ Focal cord lesion: Usually asymmetric; shows early sphincter involve- ment. ■ Rabies: Follows wild animal exposure. ■ West Nile virus. ■ Botulism: Also presents with diplopia and ocular palsies. ■ Tick paralysis: Look for an attached tick, frequently on the scalp. ■ Polio: Usually asymmetric; fever is present. ■ Toxins: Heavy metals, organophosphates. HANTAVIRUS PULMONARY SYNDROME First identified in the southwestern United States in 1993; cases have since been reported across the country. Infection follows inhalation of aerosols of dried rodent urine, saliva, or feces. The disease begins as a nonspecific febrile syndrome (sudden fever, myalgias) with rapid progression to respira- tory failure/ARDS and shock. Patients have leukocytosis, hemoconcentration, and thrombocytopenia. Diagnose by serology or by immunohistochemical staining of sputum or lung tissue. Ribavirin has been used experimentally, but mortality remains 50%. HUMAN IMMUNODEFICIENCY VIRUS (HIV) HIV targets and destroys CD4+ T lymphocytes, leading to AIDS. Risk factors include unprotected sexual intercourse, IV drug use, maternal infection, needlesticks, and mucosal exposure to body fluids; also at risk are patients who received blood products before 1985. Prognostic factors are CD4 count and HIV RNA viral load. CD4 count measures the degree of immune com- promise and predicts the risk of opportunistic infections; viral load measures HIV replication rate, gauges the efficacy of antiretrovirals, and predicts CD4 count decline. [...]... 1963 to 19 67) 466 FIGURE 11.11 Rocky Mountain spotted fever (Reproduced, with permission, from Braunwald E et al Harrison’s Principles of Internal Medicine, 15th ed New York: McGraw-Hill, 2001: Plate IID-45.) DIAGNOSIS ■ ■ ■ FIGURE 11.12 2° syphilis (Reproduced, with permission, from Kasper DL et al Harrison’s Principles of Internal Medicine, 16th ed New York: McGraw-Hill, 2005: 979 .) 4 67 I N FECTIOUS... center (Reproduced, with permission, from Kasper DL et al Harrison’s Principles of Internal Medicine, 16th ed New York: McGraw-Hill, 2005: 890.) 464 FIGURE 11.9 Condylomata lata in 2° syphilis (Reproduced, with permission, from Kasper DL et al Harrison’s Principles of Internal Medicine, 16th ed New York: McGraw-Hill, 2005: 979 .) ■ based gait and foot slap), Argyll Robertson pupil (an irregular, small pupil... Other: Acinetobacter FIGURE 11.6 Pneumococcal pneumonia This Gram-stained sputum sample shows many neutrophils and lancet-shaped gram-ᮍ cocci in pairs and chains, indicating infection with S pneumoniae (Reproduced, with permission, from Kasper DL et al Harrison’s Principles of Internal Medicine, 16th ed New York: McGrawHill, 2005: 810.) 454 Gram-ᮎ Rods ■ ■ ■ ■ ■ Enterobacteriaceae (lactose fermenters): E... lymphocytes (see Figure 11.4) in 70 % of cases (WBC 12,000–18,000 and occasionally 30,000–50,000); thrombocytopenia; mildly elevated LFTs Heterophil antibodies (Monospot) are found in 90% of cases (may initially be ᮎ and then turn ᮍ in 2–3 weeks) Other EBV serologies are rarely needed Anti-VCA IgM is ᮍ at presentation; anti-EBNA and anti-S antibodies are ᮍ in 3–4 weeks Anti-VCA IgG antibodies are ᮍ if patients... gram-ᮎ bacilli ampicillin +/− vancomycin c Chloramphenicol (N meningitidis) + TMP-SMX (Listeria) + vancomycin c Impaired cellular S pneumoniae, Ceftazidime + ampicillin +/− immunity (or alcohol L monocytogenes, gram-ᮎ vancomycin.c TMP-SMX + vancomycin c abuse) bacilli (Pseudomonas) Post-neurosurgery or S pneumoniae, S aureus, Ceftazidime + vancomycin Aztreonam or ciprofloxacin + post–head trauma gram-ᮎ... infection Because false-ᮍ results may occur (especially in low-risk populations being screened), confirm by Western blot HIV RNA viral load: Not approved by the FDA for diagnosing HIV Has high sensitivity even in patients who have not yet developed antibodies False-ᮍ results may occur, usually in the form of a low copy number (e.g., < 10,000 copies/mL); true-ᮍ results in antibody-ᮎ patients with acute... Bacteroides, Fusobacterium Fusiform (long, pointed): Fusobacterium, Capnocytophaga Other: Haemophilus To remember lactose-fermenting gram-negative rods— SEEK Carbs Serratia E coli Enterobacter Klebsiella Citrobacter Acid-Fast Bacteria ■ ■ Mycobacteria Nocardia (weakly or partially acid-fast) N O N T U B E R C U LO U S (AT Y P I C AL) M YCO BAC T E R IA Nontuberculous (atypical) mycobacteria are natural... infection Constitutional symptoms 108 1 07 1000 900 Clinical latency 106 800 70 0 105 600 500 104 400 HIV RNA Copies per mL Plasma 1100 CD4+ T Lymphocyte Count (cells/mm3) I N FECTIOUS DISEASES Presents with the triad of fever, sore throat (may be severe), and generalized lymphadenopathy, often with an abrupt onset Patients may have a viral-like prodrome as well as retro-orbital headache or abdominal fullness... seen in infectious mononucleosis and other infections These reactive T lymphocytes are large with eccentric nuclei and bluish-staining RNA in the cytoplasm (Reproduced, with permission, from Braunwald E et al Harrison’s Principles of Internal Medicine, 15th ed New York: McGraw-Hill, 2001.) TREATMENT No treatment is necessary in the majority of cases Steroids are used on rare occasions for tonsillar... soon as Rocky Mountain spotted fever is suspected Diagnosis can be made by biopsy of early skin lesions or confirmed retrospectively by serologic testing Labs may show thrombocytopenia, elevated LFTs, and hyponatremia The Weil-Felix test (for antibodies cross-reacting to Proteus) is no longer considered reliable TREATMENT Doxycycline, chloramphenicol (for pregnant or doxycycline-allergic patients) COMPLICATIONS . serologies are rarely needed. ■ Anti-VCA IgM is ᮍ at presentation; anti-EBNA and anti-S antibodies are ᮍ in 3–4 weeks. Anti-VCA IgG antibodies are ᮍ if patients were previ- ously exposed. Cold agglutinins. spring. ■ Also associated with HSV-2 (recurrent—Mollaret’s meningitis) as well as with HIV and drug reactions (TMP-SMX, IVIG, NSAIDs, carba- mazepine). Unlike HSV-1 encephalitis, HSV-2 meningitis has a benign course,. therapy with ampho- tericin plus 5- ucytosine × 2 weeks followed by oral fluconazole 400 mg/day × 10 weeks. ■ Patients with HIV need long-term maintenance therapy with oral flu- conazole 200 mg/day.