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Exanthems 

Exanthems
Chapter:
Exanthems
Author(s):

Thy Thy Do

DOI:
10.1093/med/9780190862800.003.0089
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date: 04 December 2020

  1. A. Introduction

    1. a. An exanthem is an acute rash that is often accompanied by systemic symptoms such as fever and malaise. Exanthems are common in hospitalized patients and patients who seek care in the emergency department. While most of these eruptions are benign, life-threatening disorders can also cause exanthemas. In evaluating the acute skin rash, it is important to determine key aspects (Table 89.1).

      Table 89.1 Descriptive Components of Skin Rashes

      Extent

      Localized (e.g. fixed drug reaction, contact dermatitis)

      Versus Generalized (e.g. morbiliform drug eruptions)

      Distribution

      Truncal predominant (e.g., morbilliform drug eruptions)

      Acral predominant (e.g., acute graft versus host disease [GVHD])

      Predilection for skin folds (e.g., staphylococcal scalded skin syndrome [SSSS])

      Surface changes

      Scaling (e.g., atopic dermatitis, psoriasis)

      Skin sloughing (Stevens-Johnson Syndrome [SJS] or toxic epidermal necrolysis [TEN]) or SSSS

      Pustules (acute generalized exanthematous pustulosis [AGEP], pustular psoriasis)

      Bullae (immunobullous diseases such as bullous pemphigoid)

      Morphology

      Morbilliform is used to describe a “measles-like” rash characterized by small erythematous macules or papules, hence the often-used term “macular-papular” rash. Classic causes of morbilliform rashes include viral exanthems and drug eruptions. These conditions can progress to form confluent diffuse erythema over time. If confluent, consider conditions such as toxic shock syndrome (TSS) or scarlet fever.

      Special sites

      Mucosal involvement is concerning for SJS or TEN

      Hot Key

      When evaluating an exanthem, think of the ED and send an SOS signal:

      Extent, Distribution, Surface changes, mOrphology, Special sites.

    2. b. Most exanthems are pink to red/brown in color. It is important to determine whether this is blanchable erythema, which implies vasodilation (typically seen in inflammatory processes), as opposed to nonblanchable purpura (typically seen in hemorrhage).

      Hot Key

      The best way to determine blanchability is to place a glass microscope slide (or another transparent object) onto the lesion while applying pressure. You will be able to tell quickly whether the lesion blanches.

    3. c. Purpuric lesions do not blanch with pressure because they represent extravasation of blood in the tissue (hemorrhage). Purpura may be caused by inflammation or occlusion of blood vessels. The differential diagnosis of purpura is extensive and may range from benign conditions such as senile purpura to life-threatening diseases such as meningococcemia. Determining the morphology (i.e., size and shape) of the purpura and whether erythema is present can help narrow the differential diagnosis. Purpura can be divided into the following subtypes:

      1. i. Petechiae are small purpuric lesions (<10 mm). Differential diagnoses include causes of thrombocytopenia, abnormal platelet function (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs]), nonplatelet etiologies (e.g., vitamin C deficiency).

      2. ii. Ecchymoses are large purpuric lesions (≥10 mm). Differential diagnoses include trauma in the setting of anticoagulation or aging/sun-damaged skin (solar/senile purpura), and von Willebrand’s disease.

      3. iii. Palpable purpura are raised and round. Early lesions may have prominent erythema due to inflammation and vasodilation of blood vessels and may therefore exhibit partial blanching. As lesions age, they tend not to be blanchable because the inflammation of vessel wall leads to damage and hemorrhage into the surrounding tissue. Differential diagnoses include vasculitis (e.g., Henoch-Schönlein purpura, lupus erythematosus, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides, discussed in Chapter 75).

      4. iv. Inflammatory retiform purpura has a reticulate or net-like appearance (livedo reticularis), and early lesions often have prominent erythema. Differential diagnoses include vasculitis and conditions that cause microvascular occlusion.

      5. v. Noninflammatory retiform purpura has a reticulate or net-like appearance without prominent erythema in early lesions. These changes are due to microvascular occlusion (e.g., heparin or Coumadin skin necrosis, infection, vascular coagulopathy).

  2. B. Types of Exanthems

    1. a. Exanthems caused by drugs

      1. i. Morbilliform drug eruption. Any drug can cause a morbilliform rash; however, penicillins and sulfonamides are the more common culprits. The skin reaction is usually symmetric and involves the torso and upper extremities. Over time, the rash becomes more confluent centrally and moves “outward” to acral sites. The rash typically develops within 7–14 days of starting a new medication but can appear sooner in cases of inadvertent rechallenge (i.e., exposure in a sensitized host). Occasionally the rash may appear a few days after stopping the offending medication. Fever, pruritus, lymphadenopathy, and eosinophilia are sometimes present. Spontaneous resolution usually occurs within 1–2 weeks of stopping the culprit medication.

        Hot Key

        Check for mucous membrane involvement and painful, dusky skin, which may indicate the development of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).

      2. ii. Drug hypersensitivity syndrome (DHS) or drug rash with eosinophilia and systemic symptoms (DRESS). Common causes are anticonvulsants, sulfonamides, and allopurinol. The presentation is often a morbilliform rash with fever and internal organ involvement including lymphadenopathy (75%), eosinophilia (30%), abnormal liver tests (up to 90%), and heart, lung, and kidney involvement. Unlike typical morbilliform drug eruptions, DHS or DRESS usually develops 2–8 weeks after exposure to the medication and may continue for weeks to months despite drug withdrawal. The appearance of the rash does not necessarily correlate with degree of organ involvement or severity of illness. Mortality is estimated at about 10%, most often from acute liver failure, multiorgan failure, and fulminant myocarditis.

        Hot Key

        Facial edema is an early finding in DRESS. The liver is the most frequently affected visceral organ. Endocrine abnormalities, especially thyroiditis, may occur as long-term sequelae. Therefore, thyroid function should be routinely screened for at least 2 years after recovering from DRESS syndrome.

    2. b. Exanthems caused by infection

      1. i. Viral infections (e.g., rubeola [measles], rubella, parvovirus, Epstein-Barr virus, echovirus, Coxsackie virus, adenovirus, and early HIV) are the most common infectious causes of morbilliform rashes.

        Hot Key

        Viral exanthemas are usually preceded by fever and constitutional symptoms.

      2. ii. Bacterial causes of morbilliform eruptions include typhoid fever and secondary syphilis. Early rickettsial and meningococcal disease can present with a morbilliform rash but often have purpuric lesions. If you suspect rickettsial or meningococcal disease, begin empiric antibiotics while awaiting the definitive diagnosis because of the high mortality associated with these conditions (see Chapter 50).

    3. c. Exanthems caused by toxins

      1. i. Scarlet fever. Patients with a β‎-hemolytic streptococcal (group A) pharyngitis or tonsillitis can develop “scarlet fever” (so-called because of its characteristic confluent erythema with sandpaper-like texture). Mediated by an erythrotoxin, the rash usually begins on the neck and upper chest and spreads over the extremities and abdomen. Circumoral pallor and a strawberry tongue are characteristic findings, as is desquamation of involved areas in 5 days.

      2. ii. Toxic shock syndrome (TSS) is a life-threatening multisystem disorder caused by toxin-producing strains of Staphylococcus aureus or group A Streptococcus. TSS is most commonly described in the context of tampon use in menstruating women but can occur in other conditions, including wound infections or retained foreign objects. It is characterized by fever, diffuse erythematous macules or erythroderma with acral desquamation, hypotension, and involvement of three or more organs, including the gastrointestinal (nausea, vomiting, diarrhea, elevated liver enzymes), musculoskeletal (myalgias, arthralgias, myositis), renal (acute renal failure), and pulmonary (acute respiratory distress syndrome) systems. Mucous membrane (nonexudative conjunctivitis, strawberry tongue) involvement may also occur.

        Hot Key

        The rash of TSS is accentuated in the flexural folds. The rash of staphylococcal scalded skin syndrome (SSSS) also occurs in flexural folds but usually blisters within 24–48 hours of the onset. The blisters rupture and leave a burned appearance; hence the name “scalded skin.”

      3. iii. Kawasaki disease (see Chapter 75) is a multisystem disorder with inflammation of small and medium-sized blood vessels, including the coronary arteries. The etiology is unknown, but it often occurs in children younger than 5 years of age. Clinical manifestations include high-grade fever for several days, conjunctivitis, mucous membrane involvement, edema of the hands and feet, cervical lymphadenopathy, and a rash that is most prominent on the trunk. The rash can be morbilliform or begin with confluent erythema. Although usually self-limited within 4–8 weeks, 20% of untreated cases develop coronary artery damage, and up to 2% of patients may die from myocardial infarction. Standard treatment includes intravenous immunoglobulin (IVIG) and aspirin.

Hot Key

Kawasaki disease rarely affects adults but may occasionally occur in epidemic fashion. One theory of pathogenesis proposes that staphylococcal toxin acts as a “superantigen” that interacts with T cells.

Suggested Further Readings

Chung W-H, Wang C-W, Dao R-L. Severe cutaneous adverse drug reactions. J Dermatol 2016;43:758–66.Find this resource:

Fraison J-B, Sève P, Dauphin C, et al. Kawasaki disease in adults: observations in France and literature review. Autoimmun Rev 2016;15:242–9.Find this resource:

Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: part I. Clinical perspectives. J Am Acad Dermatol 2013;68:693.e1–e14.Find this resource:

Shands KN, Schmid GP, Dan BB, et al. Toxic-shock syndrome in menstruating women. N Engl J Med 1980;303:1436–42. (Classic Article.)Find this resource: