Condition	Key clinical features	Tests
Bullous pemphigoid	Generalized bullae, especially on trunk and flexural areas; patient usually older than 60 years27; Nikolsky sign (easy separation of epidermis from dermis with lateral pressure) usually negative	Skin biopsy with direct and indirect immunofluorescence is diagnostic and usually done
Dermatitis herpetiformis	Symmetric, pruritic, urticarial papules and vesicles that are often excoriated and isolated or grouped on extensor surfaces (knees, elbows), buttocks, and posterior scalp; most patients have celiac disease, but it is often asymptomatic; diagnosis is often delayed28	Skin biopsy with direct immunofluorescence is diagnostic and routinely done
HIV acute exanthem*	Diffuse, nonspecific, erythematous, maculopapular, nonpruritic lesions29; fever, fatigue, headache, lymphadenopathy, pharyngitis, myalgias, and gastrointestinal disturbances	Measurement of quantitative plasma HIV-1 RNA levels (viral load) by polymerase chain reaction30; HIV serology (delay at least 1 month after acute illness); skin biopsy is nonspecific and not often done†
Id reaction	Follicular papules or maculopapular or vesiculopapular rash involving forearms, thighs, legs, trunk, or face; associated with active dermatitis (e.g., stasis dermatitis) or fungal infection elsewhere	KOH preparation to diagnose dermatophyte infection; skin biopsy is nonspecific and not often done†
Kawasaki disease*	Erythematous rash on hands and feet starting 3 to 5 days after onset of fever in children younger than 8 years (usually younger than 4 years); blanching macular exanthem on trunk, especially groin and diaper area; hyperemic oral mucosa and red, dry, cracked, bleeding lips	CBC to detect elevated white blood cell and platelet counts; measurement of C-reactive protein level and erythrocyte sedimentation rate31; skin biopsy is nonspecific and not often done†
Lupus (subacute cutaneous lupus erythematosus)	Papulosquamous or annular pattern, mainly on trunk and sun-exposed face and arms; can be drug induced32	Antinuclear antibody testing; skin biopsy with direct immunofluorescence is diagnostic and often done
Lyme disease*	Erythema migrans at site of tick bite, progressing to generalized macular lesions on proximal extremities, chest, and creases (median lesion size, 15 cm); history of outdoor activities; most common in northeastern U.S. seaboard, Minnesota, and Wisconsin33	Serology; skin biopsy is nonspecific and not often done†
Meningococcemia*	Nonblanching petechiae and palpable purpura, which may have gunmetal gray necrotic centers34; usually spares palms and soles; may start as erythematous papules or pink macules	Positive cultures of blood, lesions, and cerebrospinal fluid; positive buffy coat Gram stain; skin biopsy is usually nonspecific and not often done†
Mycosis fungoides (i.e., cutaneous T-cell lymphoma)	Flat erythematous macules evolving into red scaly plaques with indistinct edges and poikiloderma (atrophy, white and brown areas, telangiectasia); can present as erythroderma (Sézary syndrome); diagnosis is often delayed; often confused with eczema35	Skin biopsy is diagnostic and routinely done
Rocky Mountain spotted fever*	2- to 6-mm macules that spread centrally from wrists and ankles and that progress to papules and petechiae; often involves palms and soles; fever, severe headache, photophobia, myalgias, abdominal pain, nausea, and vomiting; history of outdoor activities in endemic area (e.g., Oklahoma, Tennessee, Arkansas, southern Atlantic states)	Serology; skin biopsy with direct fluorescent antibody testing is diagnostic and often done, if available36
Scarlet fever*	Blanching sandpaper-like texture follows streptococcal pharyngitis or skin infection; Pastia lines (petechiae in antecubital and axillary folds); fever, vomiting, headache, and abdominal pain; most common in children	Antistreptolysin O titer; throat culture; skin biopsy is nonspecific and not often done†
Secondary syphilis*	Variable morphology, but usually red-brown scaly papules with involvement of the palms and soles; oral and genital mucosa also commonly affected	Positive syphilis serology (usually done); skin biopsy can be nonspecific and is not often done†
Staphylococcal scalded skin syndrome*	Starts with painful, tender sandpaper-like erythema favoring flexural areas, and progresses to large, flaccid bullae37; positive Nikolsky sign; most common in children younger than 6 years	Skin biopsy is diagnostic and routinely done to distinguish from toxic epidermal necrolysis, which is rare in infancy and childhood; frozen section biopsy should be considered; eyes, nose, throat, and bullae should be cultured for Staphylococcus aureus
Stevens-Johnson syndrome* Toxic epidermal necrolysis*	Stevens-Johnson syndrome: vesiculobullous lesions on the eyes, mouth, genitalia, palms, and soles; usually drug induced Toxic epidermal necrolysis: life-threatening condition with diffuse erythema, fever, and painful mucosal lesions; positive Nikolsky sign	Skin biopsy is diagnostic and routinely done for toxic epidermal necrolysis; frozen section biopsy should be considered38
Sweet syndrome (i.e., acute febrile neutrophilic dermatosis)	Red, tender papules that evolve into painful erythematous plaques and annular lesions on upper extremities, head, neck, backs of hands, and back; most common in middle-aged and older women	Skin biopsy is diagnostic and routinely done39
Toxic shock syndrome*	Diffuse erythema (resembling sunburn); fever, malaise, myalgia, nausea, vomiting, hypotension, diarrhea, and confusion; conjunctival injection, mucosal hyperemia (oral or genital); late desquamation, especially on palms and soles; most common in menstruating women or postoperative patients	CBC to detect thrombocytopenia; blood cultures; skin biopsy is nonspecific and not often done†