surface may be involved, including the eyes, lips ( Fig 68.11 ), tongue, buccal mucosa, nose, and genitalia In severe cases, pulmonary and renal involvement has also been reported Ocular manifestations include conjunctivitis with photophobia, keratitis, uveitis, or corneal ulcerations Close ophthalmologic care is essential to prevent long-term complications, such as corneal neovascularization, symblepharon, and blindness Bullae may not be obvious on mucous membranes, and often appear as a gray–white film that leaves erosions, ulcerations, and hemorrhagic crust Mucosal involvement may lead to difficulty eating, drinking, dysuria, and pain with defecation Ultimately, if scarring occurs, it can result in functional impairment from esophageal stenosis, urethral stenosis, vaginal stenosis, and anal strictures FIGURE 68.10 Confluent epidermal necrosis on the face results in diffuse desquamation and erosions Note the involvement of the lips with hemorrhagic crust and erosions (Reprinted with permission from Garg SJ Color Atlas and Synopsis of Clinical Ophthalmology—Wills Eye Institute—Uveitis Philadelphia, PA: Lippincott Williams & Wilkins; 2011.) FIGURE 68.11 Hemorrhagic crust and erosions on the lip after desquamation (Reprinted with permission from Onofrey BE, Skorin L, Holdeman NR Ocular Therapeutics Handbook Philadelphia, PA: Lippincott Williams & Wilkins; 2011.) Drugs are the most common trigger for SJS/TEN Antibiotics (trimethoprimsulfamethoxazole, minocycline), antiepileptics (carbamazepine, phenytoin, phenobarbital, lamotrigine), NSAIDs, and nevirapine are frequent triggers for SJS/TEN The first signs of SJS/TEN can present approximately to 21 days after starting the medication Similar to DHR, a genetic predisposition for SJS/TEN development may be present Since the identification of the association between HLA-B*1502 and carbamazepine-induced SJS/TEN in patients of East Asian descent, the Food and Drug Administration recommends HLA-B*1502 testing prior to carbamazepine initiation Similarly, HLA-B*5801 has been associated with allopurinol hypersensitivity and HLA-B*5701 has been associated with abacavir hypersensitivity A mucosal predominant form of SJS associated with mycoplasma infection was recently renamed Mycoplasma pneumoniae– induced rash and mucositis (MIRM) Mucositis is a prominent feature of MRIM, though the cutaneous involvement is absent or minimal As a result, the clinical course of MRIM is milder than SJS/TEN MIRM-like reactions have also been reported with influenza and Chlamydia pneumoniae infection Early MRIM may be difficult to distinguish from SJS/TEN In those cases, initiation of treatment for SJS/TEN is prudent while awaiting results from an infectious workup The differential diagnosis for SJS/TEN includes EM, staphylococcal scalded skin syndrome (SSSS), and Kawasaki disease As noted above, although SJS/TEN can have targetoid lesions, these are not the classic target lesions seen in EM Additionally, SJS/TEN usually begins on the face and trunk, rather than the extremities as in EM Likewise, although EM can have mucous membrane involvement, it does not involve two or more mucous membranes SSSS affects the superficial epidermis, resulting in superficial desquamation rather than the full-thickness epidermal necrosis seen with SJS/TEN SSSS also spares the oral mucosa, while SJS/TEN affects the oral mucosa In contrast, Kawasaki disease often has a mucosal involvement, with conjunctivitis, strawberry tongue, and dry and cracked lips However, the degree of involvement is not as severe as that seen in SJS/TEN, which may frequently consist of widespread erosions within the mouth and thick hemorrhagic crust on the lips Similar to other drug reactions, the most important step in managing SJS/TEN is stopping the causative medication Wound care is critical to decrease the risk of complications, including infection and scarring Petrolatum gauze or plain petrolatum should be liberally used to prevent scarring in all affected areas, including the lips, genitals, and anus Ophthalmology and urology should be consulted if there is suspected ocular or urethral involvement The skin should be examined daily, and signs of infection should prompt aggressive treatment because the primary cause of mortality is infection Mortality from SJS/TEN can be as high as 30%, with mortality increasing proportionally to the amount of body surface area involved Pain management and nutritional support may need to be provided parenterally since oral involvement may limit oral intake Regarding medical treatment, there is no consensus as to whether systemic steroids or intravenous immunoglobulins (IVIG) have benefit in this condition Systemic steroids have generally fallen out of favor because of the increased risk of infection and delayed wound healing IVIG is often used because it is thought to block apoptosis signaling pathways When used, IVIG is given at 0.5 to g/kg/day for to days to reach a total dose of to g/kg Recently, there is evidence that tumor necrosis factor alpha (TNFa) inhibitors may be effective for the treatment of SJS/TEN, though there have only been a few case reports of its use in pediatrics Suggested Readings and Key References Urticaria Peroni A, Colato C, Schena D, et al Urticarial lesions: if not urticaria, what else? The differential diagnosis of urticaria: part I Cutaneous diseases J Am Acad Dermatol 2010;62:541–555 Morbilliform Amstutz U, Ross CJ, Castro-Pastrana LI, et al HLA-A 31:01 and HLA-B 15:02 as genetic markers for carbamazepine hypersensitivity in children Clin Pharmacol Ther 2013;94:142–149 Chovel-Sella A, Ben Tov A, Lahav E, et al Incidence of rash after amoxicillin treatment in children with infectious mononucleosis Pediatrics 2013;131:e1424–e1427 Ferrero NA, Pearson KC, Zedek DC, et al Case report of drug rash with eosinophilia and systemic symptoms demonstrating human herpesvirus-6 reactivation Pediatr Dermatol 2013;30:608–613 Kardaun SH, Sekula P, Valeyrie-Allanore L, et al Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction Results from the prospective RegiSCAR study Br J Dermatol 2013;169:1071–1080 Acute Generalized Exanthematous Pustulosis Sidoroff A, Dunant A, Viboud C, et al Risk factors for acute generalized exanthematous pustulosis (AGEP)-results of a multinational case-control study (EuroSCAR) Br J Dermatol 2007;157:989–996 Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis Canavan TN, Mathes EF, Frieden I, et al Mycoplasma pneumoniae-induced rash and mucositis as a syndrome distinct from Stevens-Johnson syndrome and erythema multiforme: a systemic review J Am Acad Dermatol 2015;72:239– 245 Chen P, Lin JJ, Lu CS, et al Carbamazepine-induced toxic effects and HLAB*1502 screening in Taiwan N Engl J Med 2011;364:1126–1133 Ciralsky JB, Sippel KC, Gregory DG Current ophthalmologic treatment strategies for acute and chronic Stevens-Johnson syndrome and toxic epidermal necrolysis Curr Opin Ophthalmol 2013;24:321–328 Downey A, Jackson C, Harun N, et al Toxic epidermal necrolysis: review of pathogenesis and management J Am Acad Dermatol 2012;66:995–1003 Huang YC, Li YC, Chen TJ The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis ... effective for the treatment of SJS/TEN, though there have only been a few case reports of its use in pediatrics Suggested Readings and Key References Urticaria Peroni A, Colato C, Schena D, et al Urticarial... E, et al Incidence of rash after amoxicillin treatment in children with infectious mononucleosis Pediatrics 2013;131:e1424–e1427 Ferrero NA, Pearson KC, Zedek DC, et al Case report of drug rash