Fever, Hyperthermia, Chills, and Rash

FEVER

DEFINITIONS Temperature: Normal body temperature is maintained

(_37.2_C/98.9_F in the morning and _37.7_C/99.9_F in the evening) because

the hypothalamic thermoregulatory center balances excess heat production from

metabolic activity in muscle and liver with heat dissipation from the skin and

lungs.

Fever: An elevation of normal body temperature in conjunction with an

increase in the hypothalamic set point. Infectious causes are common.

Fever of unknown origin (FUO):

1. Classic FUO: Three outpt visits or 3 days in the hospital without elucidation

of a cause of fever; or 1 week of unproductive intelligent and invasive

ambulatory investigation,temperatures _38.3_C (101_F) on several occasions,

and duration of fever for _3 weeks

2. Nosocomial FUO: At least 3 days of investigation and 2 days of culture

incubation failing to elucidate a cause of fever in a hospitalized pt with temperatures _38.3_C (101_F) on several occasions and no infection on

admission

3. Neutropenic FUO: At least 3 days of investigation and 2 days of culture

incubation failing to elucidate a cause of fever in a pt with temperatures

_38.3_C (101_F) on several occasions whose neutrophil count is _500 _L

or is expected to fall to that level within 1–2 days

4. HIV-associated FUO: Failure of appropriate investigation to reveal a cause

of fever in an HIV-infected pt with temperatures _38.3_C (101_F) on several

occasions over a period of _4 weeks for outpatients and _3 days for

hospitalized pts.

Hyperpyrexia: Temperatures _41.5_C (106.7_F) that can occur with severe

infections but more commonly occur with CNS hemorrhages

ETIOLOGY Most fevers are associated with self-limited infections (usually

viral) and have causes that are easily identified.

• Classic FUO: As the duration of fever increases,the likelihood of an infectious

etiology decreases. Etiologies to consider include:

1. Infection—e.g.,extrapulmonary tuberculosis; EBV,CMV, or HIV infection;

occult abscesses; endocarditis; fungal disease

2. Neoplasm—e.g.,lymphoma and hematologic malignancies, hepatoma,

renal cell carcinoma

3. Miscellaneous noninfectious inflammatory diseases

a. Systemic rheumatologic disease or vasculitis—e.g.,Still’s disease,

lupus erythematosus

b. Granulomatous disease—e.g.,granulomatous hepatitis, sarcoidosis,

Crohn’s disease

c. Miscellaneous diseases—e.g.,pulmonary embolism,hereditary fever

syndromes,drug fever, factitious fevers

• Nosocomial FUO

Infectious—e.g.,infected foreign bodies or catheters, Clostridium difficile

colitis,sinusitis

Noninfectious—e.g.,drug fever, pulmonary embolism

• Neutropenic FUO: More than 50–60% of pts infected or at risk for bacterial

and certain fungal and viral infections

• HIV-associated FUO: More than 80% of pts infected,but drug fever and

lymphoma also possible etiologies

PATHOGENESIS Hypothalamic set point increases; pt feels cold due to

peripheral vasoconstriction and shivering that are needed to raise body temperature

to new set point; peripheral vasodilation and sweating commence when

set point is lowered again by resolution or treatment of the fever.

Fever caused by:

Exogenous pyrogens (e.g.,lipopolysaccharide endotoxin)

Endogenous pyrogens (e.g.,interleukin 1, tumor necrosis factor) induced by

exogenous pyrogens

Prostaglandin E2 (in CNS,raises hypothalamic set point; in peripheral tissues,

causes myalgias and arthralgias)

CLINICAL FEATURES Generalized symptoms: myalgias,arthralgias,

anorexia,somnolence, chills,sweats, rigors,change in mental status,rash

History A meticulous history is essential.

Symptom chronology (in case of rash: site of onset and direction and rate

of spread) in relation to medications,treatments, occupational and potential

toxic exposures,pets, sick contacts, sexual contacts, travel,diet,hobbies

Tobacco,alcohol,marijuana, or IV drug use

Trauma,tick bites, other animal bites

Transfusions,immunizations,allergies

Physical Examination Special attention to skin,lymph nodes, eyes, nail

beds, cardiovascular system,chest,abdomen, musculoskeletal system, nervous

system. Rectal and pelvic examinations must be included.

Skin examination can be especially revealing in pts with fever.

1. Type of lesion (e.g.,macule,papule, nodule,vesicle, pustule, purpura,

ulcer)

2. Classification of rash

a. Centrally distributed maculopapular eruptions (e.g.,measles, rubella)

b. Peripheral eruptions (e.g.,Rocky Mountain spotted fever, secondary

syphilis)

c. Confluent desquamative erythemas (e.g.,toxic shock syndrome)

d. Vesiculobullous eruptions (e.g.,varicella, smallpox, rickettsialpox)

e. Urticarial eruptions: Hypersensitivity reactions are usually not associated

with fever. The presence of fever suggests serum sickness,connective-

tissue disease,or infection (hepatitis B, enteroviral or parasitic

infection).

f. Nodular eruptions (e.g.,disseminated candidiasis, cryptococcosis, erythema

nodosum,Sweet’s syndrome)

g. Purpuric eruptions (e.g.,acute meningococcemia, echovirus 9 infection,

disseminated gonococcemia)

h. Eruptions with ulcers or eschars (e.g.,scrub typhus or rickettsialpox)

DIAGNOSIS

In most cases,initial history, physical examination, and laboratory

tests (including CBC with differential,ESR,electrolytes, LFTs, urinalysis,

and CXR; CT, MRI,or nuclear scans as indicated; and appropriate smears

and cultures and sampling of abnormal fluid collections) lead to a diagnosis,or

the pt recovers spontaneously. If fever continues for 2–3 weeks and repeat

physical examinations and laboratory tests are unrevealing,the pt is diagnosed

as having FUO. The approach to diagnosis of FUO is found in Fig. 36-1.

TREATMENT

The diagnosed infection should be treated appropriately. In pts with FUO,

“shotgun” empirical therapy should be avoided if vital signs are stable and

the pt is not neutropenic. Cirrhosis,asplenia, immunosuppressive drug use,

or recent exotic travel may be appropriate settings for empirical treatment.

Treatment of the fever with antipyretics may mask important clinical indicators;

examples include a relapsing pattern seen in malaria and a reversal

of the usual times of peak and trough temperatures in typhoid fever and disseminated tuberculosis. However,treatment of fever is appropriate to ameliorate

symptoms and reduce oxygen demand in pts with underlying cardiovascular

or pulmonary disease or to prevent seizures in children with a history

of febrile seizures. Antipyretic treatment should be given on a regular schedule

rather than intermittently; otherwise,it will aggravate chills and sweats.

Aspirin,NSAIDs, and glucocorticoids are effective antipyretics, but acetaminophen

is preferred because it does not mask signs of inflammation,

does not impair platelet function,and is not associated with Reye’s syndrome.

PROGNOSIS Failure to identify the source of FUO for _6 months is

generally associated with a good prognosis. Debilitating symptoms can be

treated with antipyretics.

HYPERTHERMIA

DEFINITIONS AND ETIOLOGY Hyperthermia: An unchanged setting

of the hypothalamic set point in conjunction with an uncontrolled increase in

body temperature that exceeds the body’s ability to lose heat

Heat stroke: Thermoregulatory failure in association with a warm environment

Exertional: Caused by exercise in high heat or humidity

Nonexertional: Occurs in high heat or humidity in pts taking anticholinergic

agents (e.g.,antiparkinsonian drugs, diuretics, phenothiazines)

Drug-induced: Caused by drugs such as monoamine oxidase inhibitors,tricyclic

antidepressants,amphetamines, and cocaine and other illicit agents

Malignant hyperthermia: Hyperthermic and systemic response to halothane

and other inhalational anesthetics in pts with genetic abnormality

Neuroleptic malignant syndrome: Syndrome caused by use of neuroleptic

agents (e.g.,haloperidol) and consisting of lead-pipe muscle rigidity, extrapyramidal side effects,autonomic dysregulation,and hyperthermia

EPIDEMIOLOGY In the United States,7000 deaths were attributed to

heat injury in 1979–1997. The elderly,the bedridden,persons confined to

poorly ventilated or non-air-conditioned areas,and those taking anticholinergic,

antiparkinsonian,or diuretic drugs are most susceptible.

CLINICAL FEATURES/DIAGNOSIS High core temperature without

diurnal variations in association with an appropriate history (heat exposure,

certain drug treatments) and dry skin, hallucinations,delirium,pupil dilation,

muscle rigidity,and/or elevated levels of creatine phosphokinase

TREATMENT

Physical cooling:

Sponging, fans,cooling blankets,ice baths

IV fluids,internal cooling by gastric or peritoneal lavage with iced saline

In extreme cases,hemodialysis or cardiopulmonary bypass

For malignant hyperthermia,cessation of anesthesia and administration of

dantrolene (1–2.5 mg/kg q6h for at least 24–48 h) plus procainamide administration because of risk of ventricular fibrillation. Dantrolene is also useful

in neuroleptic malignant syndrome and drug-induced hyperthermia and

may be helpful in serotonin syndrome and thyrotoxicosis.

37	Pain or Swelling of Joints

Musculoskeletal complaints are extremely common in outpatient medical practice

and are among the leading causes of disability and absenteeism from work.

Pain in the joints must be evaluated in a uniform,thorough, and logical fashion

to ensure the best chance of accurate diagnosis and to plan appropriate followup

testing and therapy. Joint pain and swelling may be manifestations of disorders

affecting primarily the musculoskeletal system or may reflect systemic

disease.

Goals for the Initial Assessment of a Musculoskeletal

Complaint (See Fig. 37-1)

1. Articular versus nonarticular. Is the pain located in a joint or in a periarticular

structure such as soft tissue or muscle?

2. Inflammatory versus noninflammatory. Inflammatory disease is suggested

by local signs of inflammation (erythema,warmth,swelling), systemic features

(morning stiffness,fatigue, fever,weight loss), or laboratory evidence

of inflammation (thrombocytosis,elevated ESR or C-reactive protein).

3. Acute (_6 weeks) versus chronic.

4. Localized versus systemic.

Historic Features

• Age,sex, race,and family history

• Symptom onset (abrupt or indolent),evolution (chronic constant, intermittent,

migratory,additive),and duration (acute versus chronic)

• Number and distribution of involved structures: monarticular (one joint),

oligoarticular (2–3 joints),polyarticular (_3 joints); symmetry

• Other articular features: morning stiffness,effect of movement, features that

improve/worsen Sx

• Extraarticular Sx: e.g.,fever, rash,weight loss,visual change, dyspnea,diarrhea,

dysuria, numbness, weakness

• Recent events: e.g.,trauma,drug administration, travel,other illnesses.

Physical Examination

Complete examination is essential: particular attention to skin,mucous membranes,

nails (may reveal characteristic pitting in psoriasis), eyes. Careful and

thorough examination of involved and uninvolved joints and periarticular structures;

this should proceed in an organized fashion from head to foot or from

extremities inward toward axial skeleton; special attention should be paid to

identifying the presence or absence of

• Warmth and/or erythema

• Swelling

• Synovial thickening

• Subluxation,dislocation, joint deformity

• Joint instability

• Limitations to active and passive range of motion

• Crepitus

• Periarticular changes

• Muscular changes including weakness,atrophy

Laboratory Investigations

Additional evaluation usually indicated for monarticular,traumatic, inflammatory,

or chronic conditions or for conditions accompanied by neurologic changes

or systemic manifestations.

• For all evaluations: include CBC,ESR,or C-reactive protein Should be performed where there are suggestive clinical features: rheumatoid factor,ANA,antineutrophilic cytoplasmic antibodies (ANCA), antistreptolysin O titer,Lyme antibodies

• Where systemic disease is present or suspected: renal/hepatic function tests,

UA

Uric acid—useful only when gout diagnosed and therapy contemplated

• CPK,aldolase —consider with muscle pain, weakness

• Synovial fluid aspiration and analysis: always indicated for acute monarthritis

or when infectious or crystal-induced arthropathy is suspected. Should

be examined for (1) appearance,viscosity; (2) cell count and differential (suspect

septic joint if WBC count _ 50,000/_L); (3) crystals using polarizing

microscope; (4) Gram’s stain,cultures (Fig. 37-2).

Diagnostic Imaging

Plain radiographs should be considered for

• Trauma

• Suspected chronic infection

• Progressive disability

• Monarticular involvement

• Baseline assessment of a chronic process

• When therapeutic alterations are considered

Additional imaging procedures,including ultrasound, radionuclide scintigraphy,

CT,and MRI,may be helpful in selected clinical settings.

Special Considerations in the Elderly Patient

The evaluation of joint and musculoskeletal disorders in the elderly pt presents

a special challenge given the frequently insidious onset and chronicity of disease

in this age group,the confounding effect of other medical conditions, and the

increased variability of many diagnostic tests in the geriatric population. Although

virtually all musculoskeletal conditions may afflict the elderly,certain

disorders are especially frequent. Special attention should be paid to identifying

the potential rheumatic consequences of intercurrent medical conditions and

therapies when evaluating the geriatric pt with musculoskeletal complaints.