Differentials
Common
Herpes simplex
History
primary or recurrent outbreak of vesicles associated with tenderness, burning, or tingling; can occur during both symptomatic and asymptomatic periods of viral shedding; history of direct contact with infected saliva or other infected secretions (common with herpes simplex virus-1 [HSV-1]), history of sexual contact (common with HSV-2), symptoms typically start within 1 week after exposure
Exam
grouped vesicles on an erythematous base, may evolve to pustules or erosions, lesions resolve within 2 to 6 weeks
1st investigation
- no initial test:
diagnosis is often made on clinical examination
Other investigations
- viral direct immunofluorescence assay:
positive
More - vesicle Tzanck smear:
multinucleated giant cells
More - vesicle viral culture:
virus detected
- lesion HSV polymerase chain reaction:
positive
More - type-specific serologic assay:
positive antibody to HSV-1 or HSV-2
More - skin biopsy:
ballooning cytoplasm of keratinocytes with marginated nuclear chromatin; multinucleated giant cells
Herpes zoster (shingles)
History
prior history of varicella infection, presents with prodrome of pain, itching, hyperesthesia followed by vesicular eruption
Exam
painful, grouped vesicles on an erythematous base in a sensory dermatomal distribution, rarely crosses midline; in immunocompromised hosts distribution may be widespread with visceral involvement in some patients
1st investigation
- no initial test:
diagnosis is often made on clinical examination
Other investigations
- direct fluorescent antibody test:
positive for varicella virus
More - vesicle viral culture:
positive varicella virus
- vesicle Tzanck smear:
multinucleated giant cells
- polymerase chain reaction:
positive for varicella DNA
- skin biopsy:
ballooning cytoplasm of keratinocytes with marginated nuclear chromatin; multinucleated giant cells
Varicella zoster, acute (chickenpox)
History
initial viremia between days 4 and 6; days 11 to 20 secondary viremia and appearance of characteristic vesicular eruption on erythematous base, often referred to as "dewdrops on rose petals," low-grade fever, malaise, and headache
Exam
successive crops of lesions appear over several days on trunk, face, and oral mucosa; typically lesions are in different stages of evolution from vesicles to crust and do not scar; hemorrhagic and bullous lesions rarely occur
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- direct fluorescent antibody test:
positive for varicella virus
More - vesicle Tzanck smear:
multinucleated giant cells
- vesicle viral culture:
positive varicella virus
More - skin biopsy:
acantholysis and degeneration of keratinocytes, intranuclear eosinophilic inclusion bodies in epithelial cells
- polymerase chain reaction:
positive for varicella DNA
Dermatophyte infections (inflammatory or bullous tinea pedis)
History
associated with wearing occlusive shoes
Exam
vesicles and bullae present on the medial foot, may evolve with superficial erosion with crust, involvement of other areas of foot not usually present
1st investigation
- lesion potassium hydroxide preparation:
positive for hyphae
- lesion fungal culture:
positive for specific dermatophyte
More
Other investigations
- skin biopsy:
periodic acid-Schiff stain positive for hyphae in stratum corneum
Scabies
History
generalized pruritus of recent onset, nocturnal itch very characteristic; may be a history of itching in other family members
Exam
pruritic papules, vesicles, pustules, and linear burrows, with excoriations, eczematization, crusting, and secondary infection; pathognomonic scabies burrow is an elevated white and serpiginous tract; rarely, tense bullae resembling bullous pemphigoid
1st investigation
- ectoparasite preparation (potassium hydroxide or mineral oil) for microscopy:
mite, eggs, or feces
Other investigations
- epiluminescence microscopy:
mite or eggs
- skin biopsy:
mite, eggs, or feces in stratum corneum, superficial and deep perivascular infiltrate with eosinophils
Impetigo
History
typically in children, may be history of increased humidity, poor hygiene, malnutrition and overcrowding, concomitant skin disease, chronic colonization with Staphylococcus aureus
Exam
non-bullous type: vesicles transient and seldom seen, erosions with yellowish to golden crusting, erythematous base, often perioral or perinasal; streptococcal form tends to have thicker and darker crusts; bullous type: bullae are ≥2 cm in diameter and initially clear, subsequently becoming turbid; buccal mucosa may be involved
1st investigation
- no initial test:
clinical diagnosis
- skin culture:
positive for Staphylococcus aureus or Streptococcus pyogenes
More
Other investigations
Friction blister
History
recent activity involving affected area (new shoes, gloves, or products)
Exam
tense bullae in area of pressure or friction
1st investigation
- no initial test:
clinical diagnosis; further tests required only if blistering is frequent, extensive, or failing to heal
Other investigations
- skin biopsy:
noninflammatory blister within stratum corneum
More
Miliaria
History
exposure to hot or humid climates, febrile illness in bedridden patient, layered clothing preventing dissipation of heat or moisture
Exam
pruritic or asymptomatic papules or vesicles
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- skin biopsy:
spongiosis with or without a vesicle within the epidermis related to the epidermal sweat duct unit
More
Eczematous dermatitis (allergic contact, nummular, and dyshidrotic)
History
personal or family history of atopy, recent exposure to chemicals, personal hygiene products, fabrics, or plant allergens (e.g., poison ivy, poison oak)
Exam
predominantly localized distribution of vesicles and papules with surrounding erythematous base, later lesions may be covered by scale or crusting
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- skin biopsy:
intraepidermal spongiosis and vesiculation, perivascular inflammatory infiltrate of lymphocytes and eosinophils in the superficial dermis
More
Thermal burn
History
recent exposure to external heat source, thermal trauma to skin, distribution correlates to site of exposure, vesicles may result secondary to transudation of serum from capillaries and edema of the superficial tissues
Exam
affected area erythematous, second-degree burns with superficial and deep forms, vesicles, and bullae
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- skin biopsy:
mild thermal burn: epidermal and dermal edema, vacuolated keratinocytes, and vascular dilation; severe burn: necrosis of keratinocytes, vesiculation, dermal thrombosis, and hemorrhage
More
Frostbite
History
recent exposure to extreme cold, fingers, toes, ears, cheeks, and nose most commonly affected
Exam
frozen part with erythema, edema, vesicles and bullae, gangrene; degree of injury directly related to temperature and duration of freezing
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- skin biopsy:
papillary dermal edema, subepidermal bullae secondary to edema, superficial and deep perivascular lymphocytic infiltrate, lesion progression from partial to full-thickness epidermal necrosis
More
Uncommon
Staphylococcal scalded skin syndrome
History
typically neonates or children under 5 years; individuals who are immunocompromised or have renal insufficiency
Exam
prodromal fever, tender skin evolve to generalized erythema with flexural accentuation and then flaccid bullae formation; Nikolsky sign (lateral pressure on unblistered skin in a bullous eruption with resultant shearing off of the epithelium) present, desquamation follows starting in flexural areas; in contrast to toxic epidermal necrolysis, does not affect oral mucosa and may be a helpful clue to diagnosis
1st investigation
- tissue culture:
Staphylococcus aureus
More
Other investigations
- skin biopsy for frozen section:
cleavage at or below stratum granulosum, no inflammatory cells in bullae or dermis
More
Epidermolysis bullosa
History
recurrent episodes of blistering, especially over joints and acral location with minor trauma, family history of similar condition; different subtypes can be associated with internal organ and mucosal involvement
Exam
epidermolysis bullosa simplex (EBS): blistering, milia, and scarring on body parts subject to repeated trauma (elbows, knees, hands, feet); junctional epidermolysis bullosa (JEB): widespread bullae and denudation with periorificial granulation tissue at birth; dystrophic epidermolysis bullosa (DEB): painful lesions, sub lamina densa blisters, heals with dystrophic scarring and milia; in recessive forms (RDEB) contractures and deformities result
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- skin biopsy:
cell-poor intra- or subepidermal blister
More - electron microscopy:
distinguish level of split: EBS - intraepidermal; JEB - lamina lucida; DEB - anchoring fibrils
More - immunoepitope and genetic mapping:
specific gene mutations and level of defect
More - DNA mutation analysis:
specific gene mutations
More
Coma bullae
History
coma from trauma, illness, or an overdose of a narcotic drug
Exam
erythema with vesicles or bullae at sites subjected to pressure (hands, wrists, scapulae, sacrum, knees, heels)
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- skin biopsy:
epidermal necrosis with intra- or subepidermal noninflammatory blister, sweat gland necrosis in underlying dermis
More
Nutritional deficiencies (zinc, biotin, niacin, essential fatty acids)
History
inherited or acquired deficiency, breastfed newborns, history of parenteral nutrition, characteristic cutaneous finding is a photosensitive eruption (preferentially involving the face, neck, upper chest, dorsal hands, and extensor forearms), which worsens in spring and summer[43]
Exam
dermatitis is bullous or pustular, periorificial and acral locations, associated erythematous eroded, crusted patches; with repeated sun exposure, the involved areas become thickened, scaly, and hyperpigmented
1st investigation
- serum levels of suspected agent:
decreased levels of zinc, biotin, essential fatty acid, or niacin
More
Other investigations
- skin biopsy:
pallor and vacuolization of upper third of epidermis, may form noninflammatory subcorneal bullae
More
Porphyria cutanea tarda
History
photosensitivity, fragility of sun-exposed skin that results in blistering and erosions of the dorsal hands, forearms, ears, feet, and face; ingestion of alcohol, estrogens, and polychlorinated cyclic hydrocarbons exacerbates condition
Exam
tense blisters on sun-exposed skin, heal with scarring, dyspigmentation, and milia; hypertrichosis, sclerodermatous thickenings, and scarring alopecia
1st investigation
- serum porphyrins:
>5 micrograms/dL
More - 24-hour urine collection:
urine porphyrin level >1000 micrograms/dL over 24-hour period, reddish-pink color with Wood lamp exam on gross exam
Other investigations
- skin biopsy:
subepidermal noninflammatory blister, festooning of dermal papillae
More - direct immunofluorescence:
granular deposits of IgG, C3, and IgM in capillary wall, dermal-epidermal junction
More - high-performance liquid chromatography (HPLC):
if the total porphyrins are elevated, urine porphyrins are fractionated by HPLC, showing a characteristic predominance of uroporphyrin and heptacarboxyl porphyrin
Pseudoporphyria cutanea tarda
History
hemodialysis, drug exposures (nonsteroidal anti-inflammatory drugs, furosemide, nalidixic acid, tetracycline), skin fragility, photosensitivity, absence of hypertrichosis, and skin sclerosis
Exam
bullae on sun-exposed body areas (face, ears, dorsal hands, forearms)
1st investigation
- serum porphyrins:
normal
- 24-hour urine collection:
urine porphyrin levels normal
Diabetic bullae (bullosis diabeticorum)
History
longstanding history of diabetes, spontaneously healing blisters within 4 to 5 weeks of onset
Exam
painless noninflammatory blisters typically on acral locations, including amputation sites
1st investigation
- no initial test:
clinical diagnosis
Incontinentia pigmenti
History
X-linked dominant, female infant with vesicles in a patterned distribution (Blaschko lines - these are thought to represent pathways of epidermal cell migration and proliferation during fetal development), blisters present at birth or develop during the first 2 weeks of life; cutaneous features evolve through 4 stages from infancy to adolescence (vesicles disappear by 6 months of age in 80% of infants)[56]
Exam
noninflammatory vesicles in a patterned distribution (Blaschko lines), abnormalities of teeth, eyes, hair
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- skin biopsy:
epidermal spongiosis with eosinophils and necrotic keratinocytes
More - genetic mutation mapping:
X-linked dominant, defect in nuclear essential modifier (NEMO) gene
Bullous ichthyosiform erythroderma (epidermolytic hyperkeratosis)
History
presents at birth, or shortly after, with erythema, blistering, or peeling; may be confused with staphylococcal scalded skin syndrome or epidermolysis bullosa
Exam
widespread erythema, blistering and peeling infant with or without palmar-plantar involvement
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- skin biopsy:
marked hyperkeratosis, thick granular layer, coarse keratohyaline granules, and vacuolar degeneration of the upper dermis
More - electron microscopy:
clumping of keratin filaments beginning in suprabasal level
- keratin studies:
defect in keratins 1 and 10
Mastocytosis
History
acquired solitary or widespread cutaneous eruption, lesion periodically urticates and blisters then returns to original form
Exam
5 mm to 15 mm papules, yellow-brown to yellow-red in color; edema, urtication, and vesicle and bullae formation, urticaria surrounding erythematous flare when rubbed (Darier sign)
1st investigation
- skin scraping:
scraping from base of bullae demonstrates mast cells (Giemsa or Wright stain)
More
Other investigations
- skin biopsy:
dermal mast cell infiltrates, in the papillary dermis around blood vessels, use of Leder stain, Giemsa or toluidine blue reveals granules of mast cells
More
Bullous arthropod bite reaction
History
recent arthropod exposure in a sensitized patient, typically present as grouped pruritic or asymptomatic blisters in patients who are otherwise well
Exam
grouped pruritic or asymptomatic blisters, distribution and location of the lesions usually localized to a specific area of the body (depending on causative arthropod)
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- skin biopsy:
epidermal spongiosis, focal parakeratosis and papillary dermal edema, subepidermal blister with eosinophils, superficial and deep perivascular infiltrate of lymphocytes and eosinophils in dermis
- direct immunofluorescence:
negative
More - CBC, HIV screening:
may demonstrate hematologic or immunologic derangement
More
Erythema multiforme
History
ingestion of new medications in the days or weeks before onset, implicated medications include antibiotics (trimethoprim-sulfamethoxazole), anticonvulsants (lamotrigine), nonsteroidal anti-inflammatory drugs, and allopurinol
Exam
characterized by atypical targetoid lesions, macules, vesicles, bullae on palms and soles; may be generalized
1st investigation
Other investigations
- skin biopsy (frozen section):
lichenoid interface dermatitis, infiltrate mostly lymphocytes with accompanying exocytosis and spongiosis in epidermis, necrotic keratinocytes in epidermis, partial to full-thickness epidermal necrosis with progression, intraepidermal vesiculation, subepidermal blisters, spongiosis, and vacuolar degeneration of the basement membrane zone
More - direct immunofluorescence:
granular staining C3 along basement membrane zone and papillary dermal vessels, IgM and C3 reactivity for intraepidermal cytoid bodies
More
Stevens-Johnson syndrome
History
more fulminant form of erythema multiforme with systemic and mucosal involvement of <10% of body surface area, severe mucocutaneous reaction with prodrome of fever, malaise, chills, 1 day to 2 weeks before onset, commonly implicated medications are antibiotics (trimethoprim-sulfamethoxazole), anticonvulsants (lamotrigine), nonsteroidal anti-inflammatory drugs, and allopurinol
Exam
palms, soles, and extensor surfaces with macules, may evolve to papules, vesicles, bullae, urticarial plaques, or confluent erythema; center of lesions purpuric, vesicular, or necrotic imparting targetoid appearance, secondary infection follows; oral, ocular, and genitourinary mucosal surfaces require immediate subspecialty evaluation
1st investigation
- serum electrolytes, BUN, and creatinine:
normal, may be elevated
More - cultures:
blood, urine, wound
More - skin biopsy (frozen section):
lichenoid interface dermatitis; infiltrate mostly lymphocytes with accompanying exocytosis and spongiosis in epidermis, necrotic keratinocytes present as lesions progress, partial to full-thickness epidermal necrosis, intraepidermal vesiculation, subepidermal blisters due to spongiosis, and vacuolar degeneration of the basement membrane zone occur
More - direct immunofluorescence:
granular staining C3 along basement membrane zone and papillary dermal vessels, IgM and C3 reactivity for intraepidermal cytoid bodies
More
Other investigations
- abdominal ultrasound, esophagogastric duodenoscopy, flexible sigmoidoscopy:
may be normal
More
Toxic epidermal necrolysis
History
prodrome of fever, malaise, chills, 1 day to 2 weeks before onset of mucocutaneous lesions that often precede skin lesions, commonly implicated medications are antibiotics (trimethoprim-sulfamethoxazole), anticonvulsants (lamotrigine), NSAIDs, and allopurinol
Exam
generalized erythema followed by desquamation involving >30% of the skin surface, mucosal membranes affected can cause respiratory failure, genitourinary lesions, and GI hemorrhage; ocular damage including blindness, oral involvement with dehydration, hypovolemia, acute tubular necrosis, and shock
1st investigation
- serum electrolytes, BUN, and creatinine:
normal, may be elevated
More - cultures:
blood, urine, wound
More - skin biopsy (frozen section):
lichenoid interface dermatitis; infiltrate mostly lymphocytes with accompanying exocytosis and spongiosis in the epidermis, necrotic keratinocytes present as lesions progress, partial to full-thickness epidermal necrosis, intraepidermal vesiculation, subepidermal blisters due to spongiosis, and vacuolar degeneration of the basement membrane zone occur
More - direct immunofluorescence:
granular staining C3 along basement membrane zone and papillary dermal vessels, IgM and C3 reactivity for intraepidermal cytoid bodies
More
Other investigations
- abdominal ultrasound, esophagogastric duodenoscopy, flexible sigmoidoscopy:
may be normal
More
Amyloidosis
History
mucocutaneous manifestations in 30% to 40% of patients with primary systemic amyloidosis[57]
Exam
classic signs are periorbital ecchymosis, edema, and also face affected by petechiae and ecchymoses due to cutaneous blood vessel involvement; periorbital purpura (pinch purpura or raccoon eyes) characteristic; bullae (when present) are hemorrhagic and appear in areas of trauma, particularly the hands, forearms, and feet; lesions heal with milia and scarring
1st investigation
- serum immunofixation:
presence of monoclonal protein
- urine immunofixation:
presence of monoclonal protein
- 24-hour urine for protein:
presence of protein
Other investigations
- skin biopsy:
routine histology with amorphous eosinophilic mass in papillary dermis, loss of rete ridges, nodules or plaques extend through dermis into subcutaneous tissue with little associated inflammation, bullae (when present) are subepidermal or intradermal, typically with hemorrhage, may have infiltration of blood vessel walls and adnexal structures
More - electron microscopy:
demonstration of amyloid
More - kidney or peripheral nerve biopsy:
amyloid deposits stain positive for Congo red
More - echocardiography:
may be normal or cardiomyopathy
More
Hand-foot-mouth disease
History
mostly children of ages <10 years with history of low grade fever lasting a few days, loss of appetite, sore throat, cough, abdominal pain, diarrhea, and general malaise followed by rash
Exam
oropharynx inflamed with scattered papules, macules, vesicles, or ulcers on an erythematous base present on tongue, pharynx, buccal mucosa, gingiva, and lips; acral rash involving the palms and soles, small oval or linear gray-white vesicopustules, vesicles are flaccid and thin-walled with an erythematous halo, may occasionally be painful or pruritic, tend to ulcerate and become crusted, usually heal within 1 week
1st investigation
- no initial test:
usually a clinical diagnosis
- throat and stool culture:
may retrieve coxsackievirus or enterovirus
More
Other investigations
- CBC:
elevated WBC count
- polymerase chain reaction:
may retrieve coxsackievirus or enterovirus
Congenital syphilis
History
skin lesions within first 2 weeks of life, mother with history of secondary or tertiary syphilis
Exam
primarily acrally located vesicles and bullae, may be hemorrhagic
1st investigation
- CBC:
anemia, thrombocytopenia
- serum nontreponemal test (Venereal Disease Research Laboratory [VDRL] or rapid plasma reagin):
positive
More - cerebrospinal fluid VDRL:
positive
Other investigations
- x-ray:
osteochondritis of wrist, ankles, knees, periostitis of long bones
Linear IgA disease
History
postpubertal onset, typically in third decade of life; commonly, history of associated medication use: vancomycin, lithium, amiodarone, furosemide, statins, phenytoin, captopril, and penicillin
Exam
pruritic symmetric grouped annular, crusted erythematous papules, urticarial plaques or tense vesicles and bullae on extensor surfaces: elbows, knees, or buttocks, often have an arciform morphology referred to as a cluster of jewels, mucous membranes involved in around 60% of cases, most commonly oral cavity and conjunctiva[58]
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- skin biopsy:
subepidermal blister with rich inflammatory infiltrate, neutrophils in the tips of dermal papillae
More - direct immunofluorescence:
linear deposition of IgA at dermal-epidermal junction
- indirect immunofluorescence:
salt-split skin preparations demonstrate serum antibodies to either epidermal side (lamina lucida type) or dermal side (sublamina densa type)
Chronic bullous disease of childhood
History
onset by age 2 to 3 years and resolution typically by age 13 years
Exam
involvement of oral mucosa is common, as is involvement of the scalp; rings of grouped bullae (string of pearls), preferential involvement of the lower trunk, buttocks, genitalia, and thighs, similar morphology to linear IgA
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- skin biopsy:
subepidermal blister with rich inflammatory infiltrate, neutrophils in the tips of dermal papillae
More - direct immunofluorescence:
linear deposition of IgA at dermal-epidermal junction
- indirect immunofluorescence:
salt-split skin preparations demonstrate serum antibodies to either epidermal side (lamina lucida type) or dermal side (sublamina densa type)
Pemphigus vulgaris
History
onset 40 to 60 years of age, more common in Jewish or Mediterranean descendants; may be associated with drug use (penicillamine, captopril, penicillin, ceftazidime, beta-blockers, pyrazole compounds, progesterone, rifampin, heroin), may present as pemphigus foliaceus
Exam
flaccid, easily ruptured bullae, erosions on normal skin and mucous membranes; erythematous base located on head, neck, upper trunk, intertriginous areas, and mucosa, can begin on oral mucosa, may lead to hoarseness; painful, crusty, tendency not to heal or with hypopigmentation, no scar, Asboe-Hansen sign (bullae spread laterally with pressure) present
1st investigation
- skin biopsy:
intraepithelial blistering, acantholysis, tombstone appearance in suprabasal epidermis, minimal eosinophilic inflammatory infiltrate in dermis
More
Other investigations
- direct immunofluorescence:
intercellular IgG and variably C3, lace-like pattern
- indirect immunofluorescence:
circulating IgG autoantibodies to stratified squamous epithelium
More - immunoblot assay:
detect autoantibody desmoglein 3 (130 kD)
Pemphigus foliaceus (fogo selvagem, pemphigus erythematosus)
History
commonly presents in the fourth or fifth decade, some younger patients; central distribution (e.g., head, neck, upper torso), drugs commonly implicated (penicillamine, captopril, penicillin, ceftazidime, beta-blockers, pyrazole compounds, progesterone, rifampin, heroin)
Exam
lesions only on skin, blisters very superficial, mucous membranes not affected; flaccid easily ruptured bullae that typically do not heal, adherent scale crusts may resemble cornflakes
1st investigation
- skin biopsy:
acantholysis in stratum granulosum, minimal eosinophilic inflammatory infiltrate
More
Paraneoplastic pemphigus
History
known or occult neoplasm, frequently a B-cell lymphoproliferative disorder (e.g., non-Hodgkin lymphoma, chronic lymphocytic leukemia, Castleman disease, thymoma, Waldenstrom macroglobulinemia, and spindle cell sarcomas)
Exam
painful mucous membrane ulcerations, polymorphous blistering, may resemble pemphigus vulgaris, erythema multiforme, or lichen planus; commonly an intractable stomatitis, trunk, extremities, palms, and soles may be involved
1st investigation
- skin biopsy:
intraepithelial acantholysis, interface dermatitis, and keratinocyte necrosis
More
Other investigations
- direct immunofluorescence:
intercellular IgG and C3, lace-like pattern, linear deposition at the dermal-epidermal junction
- indirect immunofluorescence:
circulating IgG autoantibodies against stratified squamous epithelium
More - immunoprecipitation/immunoblot assay:
antibodies in sera to desmoglein 1, desmoglein 3, desmoplakin I (250 kD), desmoplakin II and envoplakin (210 kD), BPAG1 (230 kD), periplakin (190,170 kD), and plakoglobin (83 kD)
More - additional workup to evaluate for underlying malignancy:
variable findings
More - additional workup to evaluate for sequelae:
variable findings
More
Bullous pemphigoid
History
common age of onset is sixth and seventh decades of life, some childhood cases reported, affects face, hands, feet, and genitalia; drugs commonly implicated (e.g., furosemide, nonsteroidal anti-inflammatory drugs, captopril, penicillamine, and systemic antibiotics); spontaneously healing
Exam
large, tense, subepidermal bullae in groin, axillae, trunk, thighs, and flexor surfaces of forearms, often erythematous or urticarial plaques, some with localized disease on shins, bullae and erosions heal spontaneously, absent Asboe-Hansen sign
1st investigation
- skin biopsy:
subepidermal blister with eosinophil-rich inflammatory infiltrate
More
Other investigations
- direct immunofluorescence:
linear deposition of IgG and C3 at dermal-epidermal junction
- indirect immunofluorescence:
antibasement membrane zone antibodies directed against 2 hemidesmosomal antigens, bp230 and bp180
More - immunoblot assay:
target antigens BP Ag1 (230 kD) and BP Ag2 (180 kD)
Pemphigoid gestationis
History
pemphigoid gestationis occurs during the late second or third trimester of pregnancy, typically resolves on delivery
Exam
low birth weight, large, tense, subepidermal bullae in groin, axillae, trunk, thighs, and flexor surfaces of forearms
1st investigation
- skin biopsy:
subepidermal blister with eosinophil-rich inflammatory infiltrate
More
Mucous membrane pemphigoid (cicatricial pemphigoid)
History
chronic, targets skin and mucosal membranes, can result in irreversible sequelae; age of onset typically in fifth to sixth decades, more prevalent in females than males
Exam
vesicles, erosions, ulcers, commonly oral cavity and conjunctiva, cutaneous findings limited to head, neck, trunk, and extremities; untreated may affect both eyes, blindness may result
1st investigation
- skin biopsy:
dense inflammatory infiltrate, lymphocytes, eosinophils, and neutrophils present at dermal-epidermal junction, scarring in papillary dermis
Other investigations
- direct immunofluorescence:
linear deposition of IgG and C3 at dermal-epidermal junction
- indirect immunofluorescence:
autoantibodies to epidermal (BP Ag2, beta integrin) or dermal side (laminin 5)
More - immunoblot assay:
demonstrate specific autoantibodies in patient sera
Epidermolysis bullosa acquisita
History
chronic, increased skin fragility, lesions on areas of skin predisposed to trauma (elbows, knees, fingers, toes), associated with many systemic diseases including myeloma, diabetes, lymphoma, leukemia, amyloidosis, and carcinoma; typically occurs in adults; therefore, onset in childhood should raise consideration of hereditary dystrophic epidermolysis bullosa
Exam
tense blisters, serous or hemorrhagic fluid, erosions with scarring and milia formation, nail dystrophy, and scarring alopecia; targets mucosal membranes of conjunctiva, oral cavity, larynx, esophagus, and urogenital tract
1st investigation
- skin biopsy:
subepidermal blister, variable inflammatory infiltrate in upper dermis, typically neutrophils
Other investigations
- direct immunofluorescence:
linear deposition of IgG at dermal-epidermal junction
More - indirect immunofluorescence:
serum antibodies bind to dermal side of salt-split skin, differentiating it from bullous pemphigoid
More - electron microscopy:
IgG and C3 deposits in sublamina densa of basement membrane zone
- immunoblot assay or enzyme-linked immunosorbent assay (ELISA):
serum antibodies bind to components of type VII collagen (290 kD or 145 kD) same as bullous lupus erythematosus
More
Bullous lupus erythematosus
History
occurs in patients with a diagnosis of systemic lupus, sun-exposed skin is preferentially involved
Exam
lesions are not pruritic or symmetric, do not have a predilection for extensor surfaces of arms, elbows, knees, or scalp; vesicles and bullae typically photo-distributed or widespread, asymptomatic
1st investigation
- no initial test:
clinical diagnosis
Other investigations
- skin biopsy:
subepidermal blister with or without basal layer vacuolization, and a neutrophil-rich infiltrate in the blister and superficial dermis
- direct immunofluorescence:
IgG and C3 in a linear or granular pattern at dermal-epidermal junction, IgM and IgA present in 50% and 60% of cases, respectively
- indirect immunofluorescence:
serum antibodies localize to dermal side of salt-split skin as in epidermolysis bullosa acquisita
- immunoblot assay:
serum antibodies bind to components of type VII collagen (290 kD or 145 kD), as in epidermolysis bullosa acquisita
More - electron microscopy:
IgG and C3 deposits in sublamina densa of basement membrane zone
More
Dermatitis herpetiformis
History
intensely pruritic, burning sensation, chronic recurrent dermatitis, young to middle-aged adults with male predominance (2:1), strong association with gluten-sensitive enteropathy (approximately 90%) and increased risk of GI lymphoma
Exam
symmetrically grouped (herpetiform) erythematous papulovesicles, vesicles or crusts distributed on extensor surfaces of the elbows, knees, buttocks, sacrum, shoulders, and scalp; oral involvement is absent
1st investigation
- no initial test:
clinical diagnosis
Other investigations
Mpox
History
a characteristic rash that typically progresses in sequential stages (from macules, to papules, vesicles, and pustules); anorectal symptoms have been reported (e.g., severe/intense anorectal pain, tenesmus, rectal bleeding, or purulent or bloody stools, pruritus, dyschezia, burning and swelling) in recent outbreaks, and may occur in the absence of a rash; fever may be a symptom of the prodromal period (usually preceding the appearance of the rash), but may present after the rash or not at all; other common symptoms may include myalgia, fatigue, asthenia, malaise, headache, sore throat, back ache, cough, nausea/vomiting, oral/oropharyngeal ulcers; there may be a history of recent travel to/living in endemic country or country with outbreak, or contact with suspected, probable, or confirmed case within the previous 21 days before symptom onset
Exam
rash or skin lesion(s) are usually the first sign of infection; physical exam may reveal a rash or lesion(s), and possibly lymphadenopathy; rash generally starts on the face and body and spreads centrifugally to the palms and soles (it may be preceded by a rash affecting the oropharynx and tongue in the 24 hours prior that often passes unnoticed); lesions simultaneously progress through four stages - macular, papular, vesicular, and pustular - with each stage lasting 1-2 days, before scabbing over and resolving; lesions are typically 5-10 mm in diameter, may be discrete or confluent, and may be few in number or several thousand; vesicles are well-circumscribed and located deep in the dermis; the rash may appear as a single lesion in the genital or perioral areas without a prodromal phase; perianal/rectal lesions and proctitis may be present; lymphadenopathy typically occurs with onset of fever preceding the rash or, rarely, with rash onset, may be submandibular and cervical, axillary, or inguinal, and occur on both sides of the body or just one side; inguinal lymphadenopathy has been commonly reported
1st investigation
- CBC:
may show leukocytosis, lymphocytosis, thrombocytopenia
- blood chemistries:
may show low urea or other derangements
- LFTs:
may show elevated transaminases, hypoalbuminemia
- polymerase chain reaction:
positive for monkeypox or orthopoxvirus virus DNA
More - STI tests:
variable (depends on the infection present)
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