Erythema nodosum (EN) is an acute panniculitis consisting of deep, painful, bilateral erythematous nodules, usually on the lower extremities, resulting from an underlying systemic illness.
Erythema multiforme (EM) is an acute, immune-mediated mucocutaneous condition characterized by target lesions with concentric zones of color change, most commonly associated with herpes simplex virus (HSV) infection.
Stevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe immune-mediated hypersensitivity reactions characterized by diffuse bullous lesions and mucocutaneous involvement most commonly precipitated by medications such as anticonvulsants.
Staphylococcal scalded skin syndrome (SSSS) is characterized by an erythematous rash followed by diffuse epidermal exfoliation.
Purpura fulminans is a severe form of rapidly progressive purpura with multiorgan failure, usually associated with meningococcemia.
Nonaccidental trauma should be suspected if bruising occurs on non-bony prominences or in areas not normally subjected to trauma during routine child play.
Toxic shock syndrome (TSS) is an acute, toxin-mediated illness characterized by fever, erythroderma, hypotension, multiorgan involvement, and desquamation. Streptococcal TSS (STSS) is a similar disease caused by invasive group A Streptococcus (GAS). Each of these is a shock state.
Necrotizing fasciitis (NF) is a rapidly progressive, life- and limb-threatening infection by virulent bacteria with severe inflammation of the fascia and surrounding subcutaneous tissues.
Kawasaki disease (KD) is an acute, self-limited, vasculitic syndrome in children. The diagnosis is established clinically by the presence of prolonged fever and four of the following five clinical features: conjunctival injection, oropharynx erythema, cervical lymphadenopathy, hand and foot erythema/swelling, and rash.
Urticaria, often referred to as hives, appears as blanchable, pruritic, raised, well-circumscribed areas of edema and erythema involving the epidermis and dermis.
Angioneurotic edema (AE) is a self-limited localized swelling due to extravasation of fluid into interstitial tissues, most commonly involving the head, neck, hand, and gastrointestinal tract. Laryngeal involvement is life-threatening.
Dermatologic signs of systemic disease are the primary focus of this chapter. Many diseases have clinical presentations where the dermatologic manifestations play a role in helping the clinician make the underlying diagnosis. Table 95-1 is a list of systemic diseases with their corresponding dermatologic manifestations, and the sections below describe pediatric emergencies in which the dermatologic characteristics play a large role in diagnosis.
| Dermatologic Manifestation | Systemic Disease |
|---|---|
| Diffuse erythroderma and shock | Toxic shock syndrome |
| Diffuse purpura with multiorgan failure | Purpura fulminans, meningococcemia |
| Petechiae in an ill-appearing child | Sepsis, Rocky Mountain spotted fever |
| Petechiae in a well-appearing child | Immune thrombocytopenic purpura |
| Purpura in a well-appearing child | Henoch–Schönlein purpura |
| Deep, painful, bilateral erythematous nodules | Erythema nodosum |
| Target lesions with central clearing | Erythema multiforme |
| Diffuse bullae in ill-appearing child | Stevens–Johnson syndrome/toxic epidermal necrolysis, necrotizing fasciitis |
| Diffuse bullae in well-appearing child | Impetigo, tinea, poison ivy |
| Nikolsky sign | Toxic epidermal necrolysis |
| Periorbital bruising | Child abuse, neuroblastoma |
| Strawberry tongue | Scarlet fever, Kawasaki disease, toxic shock syndrome |
| Desquamation | Kawasaki disease, scarlet fever, toxic shock syndrome, staphylococcal scalded skin syndrome |
| Papulovesicular eruption | Varicella, bullous impetigo, herpes simplex virus |
| Splinter hemorrhages | Infective endocarditis |
| Urticaria, diffuse pruritus, facial flushing, malaise | Serum sickness |
| Purpura and edema of ear | Henoch–Schönlein purpura, child abuse |
| Acanthosis nigricans | Type II diabetes |
| Vesicles and bullae | Systemic lupus erythematosus |
| Erythema migrans | Lyme disease |
| Dusky discoloration of entire body, especially lips, tongue, and digits | Methemoglobinemia |
| Pyoderma gangrenosum | Inflammatory bowel disease |
Erythema nodosum (EN) is a type of acute panniculitis in children.1 It is considered a dermatologic manifestation to a variety of microbial and nonmicrobial stimuli, such as streptococcal pharyngitis, tuberculosis, fungal infections, herpes simplex virus (HSV), inflammatory bowel disease, sarcoidosis, malignancies, and occasionally drugs such as oral contraceptives and sulfonamides.
The exact mechanism of EN is unknown. Debate exists as to whether it is an immune complex disorder with deposition of IgM and C3 in the venules of the deep dermis and adipose plexus, or a delayed-type hypersensitivity reaction to a wide variety of antigens.2 In the latter scenario, a non-infective cutaneous eruption represents an inflammatory response to an underlying infection or medication exposure.3
The classic lesions of EN are deep, painful, erythematous nodules or plaques that may last several weeks. They typically occur on the extensor surfaces of the extremities (Fig. 95-1) bilaterally and symmetrically, and also occur on the calves and buttocks. Ulceration is not a feature. In the context of an underlying illness, the timing of its appearance is variable. EN may be viewed as an id reaction to a large antigen load or from release of antigen after initiation of therapy for fungal infections.4 Constitutional symptoms may be present at the onset, including fever, fatigue, and muscle and joint aches.
Management focuses on treatment of the underlying cause. Lesions gradually heal as the underlying disease is controlled. In the case of a suspected id reaction to a dermatophytic infection, treatment of the infection should be continued despite development of EN. When its etiology is not clear, symptomatic relief can be obtained with extremity elevation, nonsteroidal anti-inflammatory agents (NSAIDs), and rest.
A skin biopsy may be necessary when the diagnosis is not clear. Biopsy findings demonstrate panniculitis without vascular inflammation. Laboratory tests and imaging may be considered in the evaluation of underlying disease processes.
Erythema multiforme (EM) has been associated with many different drugs and infections, with HSV and Mycoplasma pneumoniae being the most common predisposing infections. Other infectious etiologies include Epstein–Barr virus, cytomegalovirus, adenovirus, Streptococcus pneumoniae, Salmonella species, Mycobacterium tuberculosis, histoplasmosis, and certain parasites. Drugs causing EM include sulfonamides, penicillins, anticonvulsants, and NSAIDs. A large percentage of cases will not have an identifiable cause.5
The exact pathophysiology of EM is unclear. It is thought to be an acute, immune-mediated mucocutaneous hypersensitivity response triggered by various antigens. Genetic susceptibility can be a predisposing factor in some patients with EM. In patients with HSV-associated EM, a larger percentage of patients will carry specific human leukocyte antigen (HLA) alleles. Various cytokines have also been identified to play a role, with interferon-gamma found in HSV-associated EM and tumor necrosis factor-alpha in drug-induced EM, further supporting the immune-mediated mechanism.
The characteristic lesions of EM are described as round, fixed, and erythematous, appearing symmetrically on the skin and demonstrating dusky central clearing known as “target” lesions (Fig. 95-2). The lesions are distributed acrally but can also be found on the trunk, with a predilection for extensor surfaces. They can change and morphologically evolve during the course of the illness. They are sometimes accompanied by oral, genital, or ocular mucosal erosions, or a combination of these. The presence or absence of mucosal involvement separates EM major from EM minor. With EM major, prodromal symptoms of malaise, fever, and myalgias are common. Though EM is usually self-limited, there are recurrent cases, especially when associated with HSV infection.6 Until recently, EM was considered on a spectrum of disorders, including EM major, Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). In a consensus clinical classification, however, EM major and SJS are separate, distinct conditions with similar mucosal erosions.7
EM management varies depending on the type of presentation. In acute EM, the key to therapy includes removing the inciting agent and treating an identified illness (HSV and M. pneumoniae). Symptomatic control can be achieved with topical anesthetics and oral antihistamines. Treatment for EM major is dependent on the severity of mucosal involvement, and involves topical or systemic corticosteroids. Ocular involvement may necessitate emergent ophthalmology consultation and treatment with topical eye medications. In HSV-associated recurrent EM or idiopathic recurrent EM, continuous prophylactic antiviral therapy is recommended.6–8
Although there are no specific laboratory tests for EM, severe disease can be associated with increased erythrocyte sedimentation rate (ESR), white blood cell count, and liver enzyme levels.9 Other testing or imaging may be completed based on the suspicion of underlying diseases.
SJS and TEN are associated most commonly with medications such as anticonvulsants (especially carbamazepine, lamotrigine, phenytoin, and phenobarbital), antibiotics (especially sulfonamides, penicillins, and cephalosporins), allopurinol, and NSAIDs. HSV and M. pneumoniae are infections associated with SJS and TEN.
SJS and TEN are considered diseases on a spectrum of the same severe, idiosyncratic, cutaneous hypersensitivity reaction. Cytotoxic T lymphocytes and natural killer cells along with signaling ligands on activated T cells trigger apoptosis of keratinocytes, leading to diffuse bullous lesions and mucocutaneous involvement. The role of immune dysregulation is supported by the greater association of SJS and TEN in HIV-positive patients, and more severe reactions when an individual is subjected to the same inciting agent. The presence of HLA-B1502 antigen increases the risk of SJS and TEN induced by carbamazepine, an association specifically found in Asian populations.10 Rapid infusion of the anticonvulsant lamotrigine also triggers the apoptotic process in keratinocytes.11
SJS/TEN patients present with a 1- to 2-week prodrome of fever, malaise, arthralgia, and anorexia, occurring more commonly during the spring months. The rash of SJS/TEN starts on the trunk, followed by spread to the face and proximal extremities. The characteristic lesions generally start as macular lesions and may resemble “target lesions” similar to EM. These lesions progress to raised, purpuric lesions, and bullae. Bullae subsequently coalesce, resulting in sloughing of the epidermis (Fig. 95-3). Nikolsky sign, denudation of the skin with gentle tangential pressure, is present in areas of erythema. Ulcers and bullae may develop on any mucous membrane (eyes, nose, mouth, upper airway, gastrointestinal and genitourinary tracts). Severe dermatitis and conjunctivitis can occur in the eyes, leading to ulceration, perforation, and scarring. SJS and TEN are differentiated based on the extent of involvement. Epidermal detachment of <10% body surface area (BSA) is SJS, while 10% to 30% BSA detachment may be either SJS or TEN, and >30% BSA detachment is TEN. SJS is more common than TEN.10 Ocular scarring can be severe and extensive with TEN. Overall symptoms may last for 2 to 6 weeks.
SJS/TEN patients usually require admission to a burn or intensive care unit in order to closely monitor electrolytes and fluid balance, to perform meticulous skin care, and to provide analgesia and nutritional support. At times, airway support may be necessary when mucosal ulceration is extensive. Loss of the skin barrier predisposes to infections that require treatment, but routine antibiotic prophylaxis is not recommended.12 Intravenous immunoglobulin (IVIG) and systemic corticosteroids have been used for SJS, though this is controversial. Plasmapheresis has been used successfully in TEN. Eye involvement necessitates ophthalmologic consultation. Any known precipitating agents should be discontinued.
Similar to burn patients, SJS/TEN patients should have their electrolytes checked regularly, along with cultures of skin and blood to address secondary bacterial infections.
Staphylococcal scalded skin syndrome (SSSS) is caused by an exfoliative exotoxin-producing strain of Staphylococcus aureus. The physical exam findings result from the delivery of this toxin through the circulation to the skin. It most commonly presents in infants and children younger than 5 years of age.10
The exotoxin is carried through the circulation to the skin, where it targets the epidermal granular cells and activates a serine protease that cleaves the cell adhesion molecule desmoglein. Keratinocyte damage results in epidermal separation. The location of separation in SSSS is mid-epidermal, as compared to TEN, which is sub-epidermal at the dermal–epidermal junction. In localized SSSS, S. aureus enters the skin through a disruption, causes local infection, and releases exfoliative toxins. In generalized SSSS, exfoliative toxin circulates throughout the body from a colonization site (e.g., nares, groin, and umbilicus) or local infection (e.g., wound infection, septic arthritis, and osteomyelitis) and results in large areas of exfoliation.13
SSSS usually starts with prodromal symptoms including pharyngitis and conjunctivitis, and is soon followed by fever, malaise, and a blistering skin eruption. The area rapidly enlarges and coalesces, appearing similar to sunburn, which usually starts over the face, neck, axillae, and groin. Large, superficial bullae then form over the erythematous areas and rupture. The skin is exquisitely tender and fragile. Gentle rubbing of the skin results in desquamation of the epidermis, exposing a moist red base with the characteristic scalded appearance (Fig. 95-4). In infants and preschool children, the lesions are limited to the upper body, but in newborns, the entire cutaneous surface is involved (Ritter disease).
Patients with severe SSSS are managed similarly to burn patients because of the increased risk of fluid and electrolyte losses through the exposed skin, and due to the risk of secondary infection. Unlike burn patients, however, the mainstay of treatment for SSSS is the rapid initiation of antibiotics. IV nafcillin (200 mg/kg/day) is the drug of choice since it adequately treats infections caused by penicillinase-producing Staphylococci. Other options for antibiotic therapy include cefazolin (100–150 mg/kg/day) and clindamycin (30 mg/kg/day). Skin tenderness can be relieved by local and systemic agents. Due to the fragile nature of the skin, handling should be minimized, and pressure-relieving mattresses can be utilized. Corticosteroids are contraindicated.12,13 SSSS carries an 11% mortality rate in children with severe extensive skin involvement; however, the majority of the cases occur without sequelae or scarring.12
Blood cultures, as well as cultures from the nose, nasopharynx, conjunctivae, and external ear canal, may isolate the offending pathogen.
