Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine (94 page)

FEVER OF UNKNOWN ORIGIN (FUO)

Definition & etiologies

•
Fever
(as per above def) on >1 occasion during ≥3 wk &
no dx
despite 1 wk of evaluation • More likely to be
subtle manifestation of common disease
than an uncommon disease • In Pts with HIV: >75% causes are infectious, but
rarely due to HIV itself
•
Frequent reassessment needed
to identify focal signs and progression of disease

Workup

• Focus by H&P, incl: CBC w/ diff, lytes, BUN, Cr, LFTs, ESR, CRP, ANA, RF, cryoglobulin, LDH, CK, SPEP, 3 sets BCx (off abx), U/A, UCx, PPD or IGRA, HIV Ab ± PCR, heterophile Ab (EBV serologies if
), CMV antigen, Hep serologies if LFTs abnl • Stop unnecessary meds (only 20% with a med cause have eos or rash), reassess 1–3 wk • Imaging: CXR, chest & abd CT, consider tagged WBC, gallium scan, PET, TTE, LENI • Duke’s criteria for endocarditis (qv) have good Se & Sp in Pts with FUO

• Consider temporal artery bx if ↑ ESR and age >60, particularly if other s/s • ? Bone marrow aspirate & bx (esp. if signs of marrow infiltration) or liver bx (esp. if ↑ Af): even w/o localizing s/s, yield may be up to 24% (path and culture) (
Archives
2009;169:2018) • Pursue abnormalities raised by above w/u (eg, bx, MRI, etc., for dx,
not
screening)
Treatment

• Empiric abx
not
indicated (unless Pt neutropenic) • Empiric glucocorticoids not indicated unless strong suspicion for specific rheumatologic dx • Up to 30% of cases remain undiagnosed, most spontaneously defervesce (wks to mos)

FEVER AND RASH

Approach to diagnostic workup

•
Meningococcemia, IE, RMSF, sepsis, toxic shock require immediate dx & Rx

• Workup: CBC w/ diff, lytes, BUN/Cr, LFTs, LDH, CK, U/A, HIV Ab ± PCR, BCx (off abx)

• To narrow Ddx: characterize time course of rash, progression & morphology (ie, vesicular, maculopapular, pustular, purpuric, ulcerative) •
Erythema multiforme
: symmetric “target” lesions often of palms, soles, & mucous memb

Infxn etiol: HSV 1/2,
Mycoplasma
, syphilis, tick borne diseases,
etc.

Non-infxn etiol: meds (eg, NSAIDs, sulfa), malignancy, autoimmune & rheum disease

•
Erythema nodosum
: tender erythematous or violaceous nodules usually symmetric on LE

Infxn etiol: Strep, TB, EBV,
Bartonella
, HBV, psittacosis, fungal,
L. venereum
,
etc.

Non-infxn etiol: sarcoidosis, IBD, Behçet’s, other rheum, pregnancy/OCP use

• Pursue specific dx based on exposure hx & exam, including serologies, viral swab PCR, antigen tests and possibly skin biopsy ± exam of vesicular or bullae fluid if present • Etiologies more broad in immunosupp. Pts, and dx approach usually more extensive; higher risk of critical illness due to disseminated or rapidly progressive infxns

Treatment

• Empiric abx are
not
indicated (unless Pt neutropenic or critically ill)

FEVER IN A RETURNED TRAVELER

Definition & etiologies

• Febrile illness after recent travel outside of U.S./Canada; Ddx is extensive:

• Pts visiting friends and relatives abroad are most likely to contract illness during travel • Emerging pathogens: Influenza occurs year round in the tropics. Chikungunya and dengue w/ ↑ areas of transmission, hemorrhagic fevers primarily in Central Africa.

• Consider domestic infxns, STIs, & non-infxn causes. Enteric parasites rarely cause fever.

Select clinical manifestations

•
Malaria
: nonspecific symptoms including diarrhea, myalgias, cough, altered mental status •
Dengue
: nonspecific symptoms including headache, severe myalgias, rash/petechiae •
Typhoid
: constipation, abdominal pain, possible rash, relative bradycardia •
Rickettsial disease
: headache, myalgias, lymphadenopathy, possible rash/eschar
Workup

• Routine testing: CBC w/ diff, lytes, LFTs, BCx, UA, rapid malaria test

•
Fever in a traveler from a malaria zone is malaria until proven otherwise; consider hospitalization and empiric Rx.
One
smear does
not
r/o malaria.

• Other tests based on s/s, labs, exposure, incubation period, geography and seasonality. O&P exam, CXR, blood smears for filaria/Babesiosis/
Borrelia
, serologies, STI & HIV, PPD or IGRA, bone marrow aspirate, bx of lymph nodes or skin lesions, CSF studies.

NOTES

PITUITARY DISORDERS

HYPOPITUITARY SYNDROMES

Panhypopituitarism

• Etiologies

Primary
: surgery, radiation, tumors (primary or metastatic), infection, infiltration (sarcoid, hemochromatosis), autoimmune, ischemia (including Sheehan’s syndrome caused by pituitary infarction intrapartum), carotid aneurysms, cavernous sinus thrombosis, trauma

Secondary
(hypothalamic dysfunction or stalk interruption): tumors (including craniopharyngioma), infection, infiltration, radiation, surgery, trauma

• Clinical manifestations

Hormonal
: acute → weakness, easy fatigability, hypotension, polyuria and polydipsia; chronic → bradycardia, sexual dysfxn, loss of axillary & pubic hair, wt loss, amenorrhea

Mass effect
: headache, visual field Δs, cranial nerve palsies, galactorrhea

Apoplexy
(pituitary hemorrhage or infarction, usually w/ underlying pituitary adenoma): sudden headache, N/V, visual field Δs, cranial nerve palsies, meningismus, Δ MS, hypoglycemia, hypotension

• Diagnostic studies

Hormonal studies
chronic:
↓ target gland hormone + ↓ or normal trophic pituitary hormone
acute:
target gland hormonal studies may be
normal partial hypopituitarism is more common than panhypopituitarism

Pituitary MRI

• Treatment

Replace deficient target gland hormones

Most important deficiencies to recognize and treat in inPts are
adrenal insufficiency
and
hypothyroidism;
if both present, treat with glucocorticoids first, then replace thyroid hormone so as not to precipitate adrenal crisis

↓ ACTH

• Adrenal insufficiency similar to 1° (see “Adrenal Disorders”)
except:

no salt cravings or hypokalemia (b/c aldo preserved)

no hyperpigmentation (b/c ACTH/MSH is not ↑)

↓ TSH

• Central hypothyroidism similar to 1° (see “Thyroid Disorders”)
except
absence of goiter • Dx with free T
₄
in addition to TSH, as TSH may be low or
inappropriately normal
↓ PRL

• Inability to lactate
↓ GH

• ↑ chronic risk for osteoporosis, fatigue, weight gain • Dx with failure to ↑ GH w/ appropriate stimulus (eg, insulin tolerance test, glucagon stimulation) • GH replacement in adults controversial (
Annals
2003;35:419)
↓ FSH & LH

• Clinical manifestations: ↓ libido, impotence, oligomenorrhea or amenorrhea, infertility • Physical exam: ↓ testicular size; loss of axillary, pubic and body hair • Dx with: ↓ a.m. testosterone or estradiol (also assess SHBG, esp. in obese) and ↓ or normal FSH/LH (all levels ↓ in acute illness, ∴ do not measure in hospitalized Pts) • Treatment: testosterone or estrogen replacement
vs
. correction of the underlying cause
↓ ADH
(hypothalamic or stalk disease): diabetes insipidus
• Typically from mass lesion extrinsic to sella; pituitary tumor doesn’t typically present w/ DI • Clinical manifestations:
severe
polyuria,
mild
hypernatremia (
severe
if ↓ access to H
₂
O) • Diagnostic studies: see “Sodium and Water Homeostasis”