FIGURE 67.8 Frostbite Child played in the snow for a prolonged period on a cold day wearing sneakers Friction Blisters Blisters usually occur in areas predisposed to trauma or friction such as on the heels after walking or playing sports or due to new, possibly poorly fitted, shoes However, a persistent history may suggest EB, which may not always present in infancy in milder subtypes such as EB simplex as discussed above See Table 67.2 for differentiation of the various types Occasionally, accidental burns or burns secondary to child abuse are seen Abused children may have cigarette burns or have had their feet dipped in scalding water Frostbite Fingers, toes, feet, nose, cheeks, and ears are affected by extreme cold After exposed areas are damaged by the cold temperature, symptoms occur on rewarming Erythema, swelling, and burning pain occur at first, followed by vesicles and bullae (at times hemorrhagic ( Fig 67.8 )) within 24 to 48 hours Prevention is most important with appropriate protection of these sites from extreme cold LABORATORY EVALUATION If there is no clear etiology of what led to the blister, the laboratory tests described next can be helpful Gram Stain The Gram stain of fluid from an intact blister will be positive in impetigo and in a secondarily infected lesion It will be negative, however, in all other conditions Tzanck Smear Multinucleated giant cells will be present on a Tzanck smear of material scraped from the base of an intact, freshly opened vesicle caused by herpes simplex, herpes zoster, and primary varicella The Tzanck smear is not sensitive so additional testing is required if negative Rapid Slide Test for Direct Immunofluorescence Fluorescent-tagged monoclonal antibody is applied to cells scraped from the blister base and can differentiate HSV-1, HSV-2, or varicella-zoster virus Results can be available in to hours Bacterial or Viral Cultures Cultures help confirm an etiologic diagnosis when Gram stain, Tzanck smears, and DIF are negative or indeterminate Polymerase Chain Reaction An alternative or adjunct to traditional culture techniques, polymerase chain reaction techniques allow for amplification of DNA or RNA present within a specimen and rapid identification of the etiologic pathogen, including HSV, VZV, and enterovirus The technique is useful even when the pathogen present is no longer viable Skin Biopsy For perplexing cases undiagnosed by clinical and/or simple laboratory evaluation, dermatologic consultation and skin biopsy are required If the picture on histology is compatible with erythema multiforme, DIF should be considered DIF will be negative in erythema multiforme but will be positive in bullous pemphigoid (linear IgG and C3 on the basement membrane), DH (granular IgA at tips of dermal papillae of uninvolved perilesional skin), and CBDC (linear IgA on the basement membrane) though DIF can occasionally be negative in CBDC Indirect immunofluorescence can be performed to test for circulating antibodies Circulating IgG is found in bullous pemphigoid; circulating IgA is found in CBDC CONCLUSION Vesiculobullous diseases have a variety of presentations and several key features that may help to distinguish them from one another While characteristic features in some make diagnosis straightforward, many of the blistering disorders require further diagnostic evaluation in order to confirm diagnosis Treatment is aimed at the underlying pathogenesis Suggested Readings and Key References Chandler DJ, Fuller LC A review of scabies: an infestation more than skin deep Dermatology 2019;235(2):79–90 Fine JD, Bruckner-Tuderman L, Eady RA, et al Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification J Am Acad Dermatol 2014;70(6):1103–1126 Fine JD, Mellerio JE Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part I Epithelial associated tissues J Am Acad Dermatol 2009;61(3):367–384; quiz 385–386 Fine JD, Mellerio JE Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part II Other organs J Am Acad Dermatol 2009;61(3):387–402; quiz 403–404 Juckett G Arthropod bites Am Fam Physician 2013;88(12):841–847 Lai-Cheong JE, McGrath JA Kindler syndrome Dermatol Clin 2010;28(1):119– 124 Lara-Corrales I, Pope E Autoimmune blistering diseases in children Semin Cutan Med Surg 2010;29(2):85–91 Méni C, Bruneau J, Georgin-Lavialle S, et al Paediatric mastocytosis: a systematic review of 1747 cases Br J Dermatol 2015;172(3):642–651 Mintz EM, Morel KD Clinical features, diagnosis, and pathogenesis of chronic bullous disease of childhood Dermatol Clin 2011;29(3):459–462, ix Pavlek L, Schmidt J Visual diagnosis: vesicular rash in a neonate Pediatr Rev 2017;38(9):e32–e34 Sansaricq F, Stein SL, Petronic-Rosic V Autoimmune bullous diseases in childhood Clin Dermatol 2012;30(1):114–127 Torrelo A, Alvarez-Twose I, Escribano L Childhood mastocytosis Curr Opin Pediatr 2012;24(4):480–486 CHAPTER 68 ■ RASH: DRUG ERUPTIONS MELINDA V JEN DRUG ERUPTIONS The spectrum of cutaneous drug eruptions ranges from the relatively benign, where the medication can be continued if essential, to the severe, where there can be significant morbidity and mortality Thus, prompt and accurate diagnosis is critical and can be lifesaving The primary morphology of the eruption helps guide the clinician to a diagnosis Herein, we summarize the most salient features of the most common drug reactions, with a particular focus upon their primary morphologies URTICARIA Urticaria (hives, wheals) consists of erythematous, edematous papules and plaques that can coalesce into larger polycyclic, arcuate, and annular plaques ( Figs 68.1 and 68.2 ) A key diagnostic feature is that individual lesions are transient, resolving within 24 hours, but with new lesions appearing elsewhere As they resolve, purpuric macules secondary to capillary leak and hyperpigmentation may remain Pruritus and angioedema, particularly of the eyelids, hands, and feet, are common Urticaria results from IgE degranulation of mast cells Although the most common cause of urticaria is infection, medications can sometimes trigger urticaria Urticaria typically appears within the first weeks of starting the culprit medication Cephalosporins, β-lactam antibiotics, sulfonamides, and anticonvulsants are common causes of drug-induced urticaria Some medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), may cause urticaria through both immunologic and nonimmunologic pathways (via increased leukotriene synthesis) Urticaria is often confused for erythema multiforme (EM) The key features differentiating urticaria from EM are morphology, individual lesion duration, symptomology, and distribution Urticaria can be annular, polycyclic, and arcuate, but does not have the classic target appearance of EM Additionally, urticaria does not vesiculate, while the central areas of EM lesions may be bullous As noted above, individual lesions of urticaria last less than 24 hours, while lesions of EM are fixed and take several days to resolve If symptomatic, urticaria is pruritic while EM may itch or burn Urticaria can occur anywhere on the body,