Urgent message: The broad differential diagnoses in patients presenting with rash and fever range from minor conditions to life threatening illnesses, requiring the urgent care provider to make prompt but valid assessment with minimal diagnostic tools.
Kosta G. Skandamis, MD
The combination of fever and rash is so common that it may sometimes seem to be a daily occurrence
in the urgent care setting. Nonetheless, the extensive differential diagnosis requires the provider to be
vigilant for life-threatening conditions that may be anything but common, using the minimal diagnostic
tools at hand in the typical urgent care center. Prompt, appropriate management decisions are required
to effect the best possible outcomes. Initial evaluation requires a detailed history that includes:
- age of the patient
- season of the year
- recent travel
- certain activities, such as camping
- exposure to insects or animals
- ill contacts
- current and recent medications
- immune state of the individual.
Being able to recognize and describe lesions correctly, including primary and secondary characteristics, is the first step in the search for the correct diagnosis.
Common Lesions
It is beyond the scope of this article to review the various dermatologic lesions and their presentations, but we all must know the difference between macules and papules, and cysts, vesicles, or bullae. Details to consider include site of onset of the lesion, distribution and progression, timing of onset in relation to fever, and presence or absence of pruritus or pain. In addition, the provider should evaluate the overall appearance of the patient, paying particular attention to signs of toxicity, nuchal rigidity, adenopathy, neurologic dysfunction, and ophthalmic or genital lesions. Specific laboratory tests may not be available in the urgent care setting, but a CBC, sedimentation rate, calcium-magnesium-phosphate, blood cultures, and serology testing may become useful later on in the evaluation of the illness and exclude or confirm conditions such systemic lupus erythematosus, rheumatoid arthritis, syphilis, HIV, etc. In order to reach a correct diagnosis, the provider should adapt a way of categorizing the conditions that present with fever and rash. This can be by rash type, age of the patient, season of the year, exposure to animals, insects, or medications, by sexual history, etc. Here, we will summarize the conditions according to the rash type, provide pictures of rashes, and provide certain diagnostic clues. We will spend more time discussing the few conditions that are true medical emergencies and must be recognized promptly by the urgent care provider.
Maculopapular Eruptions
Maculopapular eruptions are seen most frequently in viral illnesses, immune-mediated syndromes, drug reactions, and bacterial infections. They include:
Rubeola (measles). Dark red maculopapular rash that starts on the face and spreads to the torso and
extremities (Figure 1). Becomes confluent and fades in five to six days. Most common in schoolage
children. Prodrome symptoms include three to four days of fever, coryza, cough, malaise and Koplik’s
spots. Treatment consists of supportive measures and vitamin A supplementation in order to decrease total mortality and complications, in the following dosages:
• • 6 months to 2 years of age: 100,000 units
• >2 years of age: 200,000 units
• The appropriate dose should be repeated the
next day.
Rubella. Light red/pink macules and papules that start on the forehead and spread to the extremities. Rash fades in three days. Most commonly affects young, non-immune adults. Extremely dangerous during gestation. Prodrome uncommon, extensive lymphadenopathy and Forchheimer’s spots helpful in diagnosis. Generally, picture less toxic than in measles. Symptomatic treatment: antipruritics, antipyretics. Most significant sequelae are the stillbirths, fetal anomalies, and therapeutic abortions that result when rubella occurs during the first trimester.
Erythema infectiosum (fifth disease) due to human parvovirus B19. Affects mostly children 3 to 12 years of age, who present with bright red facial rash (“slapped cheek”) which can last up to eight weeks. Non-specific prodrome of fever and malaise. Typically, rash appears after resolution of
fever. Treatment is supportive. Many infections are inapparent. Most school systems do not recommend exclusion from school.
Roseola infantum (or, exanthema subitum), due to human herpes virus 6. Mostly affects infants. Illness starts with high fever for three to four days and is followed by a diffuse maculopapular eruption that usually spares the face. Symptomatic treatment is sufficient for mild disease. Use antivirals (ganciclovir) for severe disease.
Lyme disease (Figure 6) due to spirochete. Borrelia burgdorferi is transmitted by a tick bite. All ages are at risk in endemic areas. At the site of the tick bite, a macule or papule appears, progressing to pathognomonic erythema migrans. This enlarging lesion can reach a maximum diameter of 3 cm to 68 cm (median diameter: 15 cm). Other symptoms include fever, arthralgias, myalgias, and headache. If in an endemic area, a once-daily dose of doxycycline 200 mg with food may be used prophylactically. If an attached tick or a tick bite has been identified, but the patient is not in an endemic area, the tick is not engorged, or the tick is not a deer tick, no treatment for Lyme disease is necessary.
Adult treatment in early disease:
• doxycycline 100 mg po BID, or
• amoxicillin 500 mg po TID, or
• erythromycin 250 mg po QID.
All regimens are 14 to 21 days.
Important note: Avoid doxycycline in pregnancy.
In children:
• amoxicillin 50 mg/kg/day may be given in three divided doses, or
• cefuroxime axetil 30 mg/kg/day in two divided doses, or
• erythromycin 30 mg/kg/day in three divided doses.
Drug-related eruptions can affect any gender, age, or sex and can present as any dermatologic morphology. Antibiotics (penicillins, cephalosporins, sulfamethoxazole-trimethoprim) are associated with allergic skin reactions. Barbiturates, anticonvulsants, procainamide, and quinidine are responsible for fever and hypersensitivity reactions. The rash usually appears within a week after the offending drug has been taken and resolves within few days after discontinuation.
Erythema multiforme is the most common peripheral maculopapular rash. It can be recurrent, and affects more men than women between 20- and 30-years-old. In more than half of patients, the cause is idiopathic, but radiation therapy, infections (e.g., herpes simplex, E-B virus, coxsackievirus B5, Mycoplasma, chlamydia, Salmonella typhi) and medications have also been implicated.
The typical rash in the mild form of the disease (EM minor) is dull-red, target-shaped macules and
papules (Figure 7) and involves extensor surfaces of extremities and, rarely, mucus membranes.
The severe form (EM major) is usually due to a drug reaction. The mucus membranes are always
involved, the rash tends to be bullous, usually there is fever present, and other organs (lips, mouth, eyes, pharynx, trachea, urethra, vulva) are affected. Treatment goals include:
• controlling the illness that is causing the condition
• preventing infections
• treating symptoms
• removing responsible medication.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two mucocutaneous idiopathic or drug-induced reactions characterized by skin redness, tenderness, and exfoliation. The two conditions, in which mucus membranes are involved, can be life-threatening due to multi-organ involvement. The majority of investigators believe that SJS is a maximal variant of EM major, and that TEN is a maximal variant of SJS. One to three weeks after exposure to the offending agent, mild fever and flu-like symptoms appear. There is skin tenderness present, along with conjunctival burning and itching. Initially, there is an EM-like rash (Figure 8) that rapidly becomes diffuse erythema with necrotic areas and sheet-like loss of epidermis. Later, flaccid blisters form; these spread easily with lateral pressure (Nikolsky’s sign). Eventually, detachment of epidermis leads to large, red, oozing dermis (Figure 9). Regrowth of epidermis starts within days and is competed within two to three weeks. Mucous membranes, especially the mouth, conjunctiva, and genitourinary organs are involved in 90% of cases. Involvement of the eyes can lead to keratitis, corneal ulceration, and blindness. Involvement of the anogenitalia can lead to phimosis and vaginal and anal synechiae. Sequelae in the skin can lead to painful scarring, irregular pigmentation, and nevi formation. The prognosis is related to the extent of skin necrosis, amount of fluid loss and electrolyte imbalance, presence (or not) of sepsis, and development of other complications. Mortality rate is 30% for TEN and 5% for SJS, mainly in elderly patients. Management starts with early diagnosis, discontinuation of suspected agents, and immediate referral to a burn unit or intensive care unit. Offending drugs and other drugs of the same class should never be given to these patients.
Meningococcemia. The gram-negative Neisseria meningitides is the cause of a life-threatening infection in children and young adults. Outbreaks occuramong groups that live or gather in confined areas (e.g., military bases, childcare facilities, dormitories, prisons), especially in the winter months. In addition to high fever, body aches, severe headache, somnolence, tachycardia, hypotension, nuchal rigidity, nausea, and vomiting, a rash occurs in most patients. In one review, 75% of patients had non-blanching petechial lesions; 11% had ecchymotic lesions; and 14% had no skin lesions. Mortality was higher among those with purpuric/ecchymotic lesions. Due to a high mortality rate (up to 15%, according to the Centers for Disease Control and Prevention), early diagnosis and prompt treatment are imperative. Oxygen administration, IV fluid initiation, blood cultures, spinal tap, and high doses of penicillin or a third-generation cephalosporin followed by timely transfer to the hospital are essential.
Rocky Mountain spotted fever (RMSF) is a rickettsial infection caused by Rickettsia rickettsii and transmitted to humans by a tick bite. RMSF affects mostly men during the summer months and, despite its regionally specific name, is more common in the southern Atlantic states. After two to four days of incubation, a cluster of non-specific, flu-like symptoms develops. After the fourth day, a rash develops—pinkishred macules 2 mm to 6 mm in diameter and located on the wrists, forearms, ankles, palms and soles (Figures 10a, 10b, and 10c). From there, the rash spreads centrally, becoming deep red papules. Within two to four days of onset, the lesions become petechiae. Approximately 13% of cases are identified as spotless fever. This is associated with higher mortality rate, due to delay in diagnosis. Diagnostic clues, in addition to the clinical picture, include geography, history of tick bite, leucopenia, and elevated aminotransferase. Long-term sequelae are due mostly to central nervous system involvement. Prevention can be achieved by wearing protective clothing and using tick repellants. Early pharmacotherapy is essential. Drug of choice is doxycycline 100 mg/d PO or IV twice daily. Alternatively, chloramphenicol 50 mg/kg/d to 75 mg/kg/d may be administered in four divided doses.
Resources
- Habif TP. Clinical Dermatology. 4th ed. City, USA: Mosby, An Imprint of Elsevier; 2004.
- Shapiro ED. Lyme disease: Clinical manifestations in children. UpToDate for Patients. January 2010. Available at: www.utdol.com/patients/content/topic.do?topicKey=~reSeSBDVqVDd_S.
- Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: Clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006; 43:1089-1134.
- Letko E, Papliodis DN, Papaliodis GN, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: A review of the literature. Ann Allergy, Asthma Immunol. 2005;94(4):419-436.
- French LE, Trent JT, Kerdel FA. Use of intravenous immunoglobulin in toxic epidermal necrolysis and Stevens-Johnson syndrome: Our current understanding. Int Immunopharmacol. 2006;6(4):543-549.
- Centers for Disease Control and Prevention (www.cdc.gov).
- Sexton DJ, Corey GR. Rocky Mountain “spotless” and “almost spotless” fever: A wolf in sheep’s clothing. Clin Infect Dis. 1992;15(3):439-448.
