Fever of unknown origin

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading global cause of infectious death and presents as latent infection, primary/secondary pulmonary disease, or extrapulmonary and disseminated (miliary) disease. Diagnosis rests on AFB smear, NAAT, and mycobacterial culture (the gold standard), and drug-susceptible active disease is treated with a four-drug regimen (isoniazid, rifampin, pyrazinamide, ethambutol) for 2 months followed by isoniazid plus rifampin for 4 to 7 months.

Infective endocarditis is microbial infection of the endocardium, usually a heart valve, producing vegetations that cause valve destruction, embolism, and systemic infection. Diagnosis uses the modified Duke criteria combining blood cultures and echocardiography, and treatment is prolonged targeted intravenous antibiotics with surgery for complications.

A polymicrobial, walled-off collection of pus in the peritoneal cavity or retroperitoneum, arising from perforation, postoperative contamination, diverticulitis, or appendicitis, diagnosed by contrast-enhanced CT and cured only with source control, most often percutaneous image-guided drainage plus a short course of antibiotics.

Suppurative (septic) thrombophlebitis is an infected venous thrombus with intraluminal bacteria and bacteremia, arising in peripheral IV catheters, central lines, pelvic veins, or the internal jugular vein (Lemierre syndrome). Management centers on source control (catheter removal or vein excision), prolonged antimicrobial therapy, and selective anticoagulation.

Non-Hodgkin lymphoma is a heterogeneous group of B-cell (about 85%) and T-cell lymphoid malignancies that spread noncontiguously and often involve extranodal sites, ranging from indolent follicular lymphoma to aggressive diffuse large B-cell lymphoma to highly aggressive Burkitt lymphoma. Diagnosis requires excisional or core biopsy with flow cytometry and cytogenetics, Ann Arbor staging with PET-CT, and treatment is subtype-specific, from observation to R-CHOP to intensive Burkitt regimens with aggressive tumor lysis and CNS prophylaxis.

Renal cell carcinoma is the most common kidney cancer, arising from renal tubular epithelium (most often clear cell), and is now diagnosed incidentally on imaging in most patients rather than through the classic triad of flank pain, hematuria, and mass. Contrast CT or MRI showing an enhancing solid renal mass is usually sufficient to diagnose and stage disease, and treatment is surgical for localized tumors versus tyrosine kinase inhibitors and immune checkpoint inhibitors for metastatic, chemo- and radio-resistant disease.

Adult-onset Still disease is a rare systemic autoinflammatory disorder marked by quotidian spiking fevers, an evanescent salmon-colored rash, arthritis, sore throat, and a markedly elevated ferritin. It is a diagnosis of exclusion confirmed by the Yamaguchi criteria, and treatment begins with NSAIDs, escalates to glucocorticoids, then to interleukin-1 blockade (anakinra or canakinumab) or interleukin-6 blockade (tocilizumab) for refractory disease.

Giant cell arteritis is a granulomatous large- and medium-vessel vasculitis of patients over 50 that threatens irreversible blindness through ischemic optic neuropathy. Diagnosis is clinical and must not delay treatment: start high-dose glucocorticoids immediately on suspicion, intravenous methylprednisolone pulse for visual loss, then confirm with temporal artery biopsy within 1 to 2 weeks and add tocilizumab as glucocorticoid-sparing therapy.

Polymyalgia rheumatica (PMR) is an inflammatory disorder of older adults causing aching and prolonged morning stiffness of the shoulder and hip girdles with elevated inflammatory markers, but without true weakness and with a normal creatine kinase. It is a clinical diagnosis, and treatment begins with prednisone 12.5 to 25 mg/day, which produces a dramatic response within days.

Neutropenic fever is an oncologic emergency defined as a single oral temperature of 38.3 C or higher, or 38.0 C sustained for 1 hour, with an ANC of 500/microL or lower, most often during the chemotherapy nadir. Management is empiric antipseudomonal beta-lactam therapy within 60 minutes, with vancomycin, antifungal therapy, and growth factors added only for specific indications.

Acute HIV infection, also called the acute retroviral syndrome, is the symptomatic viremic phase in the days to weeks after HIV acquisition, presenting with fever, fatigue, myalgia, rash, and pharyngitis at a time when antibody testing may still be negative. Diagnosis requires an HIV RNA viral load, and antiretroviral therapy should begin as soon as the patient is ready, regardless of CD4 count.

Osteomyelitis is bone infection from hematogenous seeding or contiguous spread, most often from Staphylococcus aureus, presenting as subacute pain with or without a draining sinus tract and confirmed by bone biopsy culture. Empiric antibiotics are withheld until biopsy in a stable patient, and treatment combines source control with 4 to 6 weeks of culture-directed antibiotics, extended to 6 weeks or indefinite suppression for hardware-associated or chronic disease.

Familial Mediterranean fever is an autosomal recessive autoinflammatory disease of pyrin, most common in Jewish, Arab, and Turkish populations, causing recurrent short attacks of fever with sterile peritonitis, pleuritis, monoarthritis, or an erysipelas-like leg rash. First-line treatment is lifelong daily colchicine, which both suppresses attacks and prevents secondary (AA) amyloidosis; colchicine-resistant disease escalates to interleukin-1 blockade.

Sarcoidosis is a multisystem granulomatous disease of unknown cause defined by noncaseating granulomas, most commonly involving the lungs and hilar lymph nodes. Most patients are asymptomatic or have a self-limited course staged by chest radiograph; symptomatic organ-threatening disease is treated with systemic glucocorticoids, with methotrexate or another steroid-sparing agent added for glucocorticoid-refractory or glucocorticoid-intolerant disease.

Systemic lupus erythematosus is a chronic multisystem autoimmune disease in which antinuclear and other autoantibodies drive immune-complex deposition and organ injury across skin, joints, kidneys, blood, serosa, and the nervous system. Diagnosis rests on a positive antinuclear antibody plus weighted 2019 EULAR/ACR criteria totaling 10 or more points. Hydroxychloroquine is lifelong first-line therapy for nearly every patient, with glucocorticoids and steroid-sparing immunosuppression added for moderate to severe or organ-threatening disease.

Factitious disorder imposed on self, formerly Munchausen syndrome, is the conscious falsification, exaggeration, or induction of physical or psychological illness in oneself with no identifiable external reward, driven by an unconscious wish to assume the sick role. Diagnosis relies on objective evidence of deception, such as a suppressed C-peptide with exogenous insulin use or a low thyroglobulin with exogenous thyroid hormone; management is non-punitive disclosure, minimal further workup, and psychiatric referral.

Pulmonary embolism is thrombus, usually from a lower-extremity deep vein thrombosis, obstructing the pulmonary arterial circulation and causing V/Q mismatch, right ventricular strain, and hypoxemia. Diagnosis follows Wells criteria (with PERC in low-risk patients) to sequence D-dimer, CT pulmonary angiography, and V/Q scanning, and management is risk-stratified anticoagulation escalating to thrombolysis or embolectomy for hemodynamic instability.

Cytomegalovirus is a ubiquitous herpesvirus that is usually asymptomatic or causes a heterophile-negative mononucleosis-like illness in healthy hosts, but reactivates to cause retinitis, colitis, pneumonitis, or encephalitis in transplant recipients and patients with AIDS; treatment is systemic ganciclovir or valganciclovir, with foscarnet and cidofovir reserved for resistance or intolerance.