There are a number of bullous diseases other than pemphigus and bullous pemphigoid that are important to recognize. Epidermolysis bullosa belongs to a family of inherited diseases where blister formation can be caused by even minor skin trauma. PLEVA (pityriasis lichenoides et varioliformis acuta) is a minor cutaneous lymphoid dyscrasia that can appear suddenly and persist for weeks to months. Dermatitis herpetiformis is a recurrent eruption that is usually associated with gluten and diet-related enteropathies. These diseases will be discussed in succession.
A 12-year-old girl with the Dowling-Meara type of epidermolysis bullosa (EB) simplex presents to her pediatrician for a URI. While examining her respiratory tract, the pediatrician notes the extensive, severe blistering over many areas of the body including, the (A) trunk, (B) extremities, and (C) the hands (Figure 157-1). She has been followed by a dermatologist since early childhood when the EB simplex was first diagnosed. It turns out that she only has a viral URI so no antibiotics are needed and standard treatment with fluids and analgesics is recommended. Her mom states that the girl has an appointment with her dermatologist next month.
A 12-year-old girl with the Dowling-Meara type of epidermolysis bullosa simplex. It is the most severe form with extensive, severe blistering over many areas of the body including, the (A) trunk, (B) extremities, and (C) the hands. (Used with permission from Richard P, Usatine, MD.)
Epidermolysis bullosa (EB) is a family of inherited diseases characterized by skin fragility and blister formation caused by minor skin trauma.1
There are autosomal recessive and autosomal dominant types; the severity of this disease may vary widely.
Onset is in childhood and in later years severe dystrophic deformities of hands and feet are characteristic (Figure 157-2).
Recessive dystrophic epidermolysis bullosa in an adolescent with a mitten deformity and flexion contractures at the wrists. (Used with permission from Kane KS, Lio PA, Stratigos AJ, Johnson RA. Color Atlas & Synopsis of Pediatric Dermatology, 2nd edition, Figure 5-3b, New York, NY: McGraw-Hill, 2009.)
Etiology and Pathophysiology
Blistering occurs at different levels for these 3 types of EB:
Epidermolysis bullosa simplex (Figure 157-1) blisters within the epidermis (most superficial).2,3
Dystrophic epidermolysis bullosa (dominant and recessive) has vesiculobullous skin separation occurring at the sub-basal lamina level of the dermis (deepest layer of all 3 types; Figures 157-2 to 157-4).
Junctional epidermolysis bullosa blisters at the dermal-epidermal junction (Figure 157-5).
Recessive dystrophic epidermolysis bullosa with loss of all her toenails starting as a young child. (Used with permission from Richard P. Usatine, MD.)
Recessive dystrophic epidermolysis bullosa in a newborn. Bullae occur at areas of minimal trauma at or near birth. (Used with permission from Kane KS, Lio P, Stratigos AJ, Johnson RA. Color Atlas and Synopsis of Pediatric Dermatology, 2nd edition, Figure 5-3a, New York, NY: McGraw-Hill, 2009.)
Junctional epidermolysis bullosa in a newborn with severe perioral, oral and GI involvement. This infant was subsequently hospitalized and despite burn unit supportive measures eventually passed away because of sepsis. (Used with permission from Kane KS, Lio P, Stratigos AJ, Johnson RA. Color Atlas and Synopsis of Pediatric Dermatology, 2nd edition, Figure 5-2c, New York, NY: McGraw-Hill, 2009.)
Acral skin fragility and blistering are the hallmark in childhood. Minor trauma can induce severe blistering. As the disease progresses initially, painful and ultimately debilitating dystrophic deformities are typical. Repeated blistering of the hands can lead to fusion of the fingers and the “mitten” deformity (Figure 157-2).
The typical distribution is acral (hands and feet), although blistering may extend proximally secondary to trauma.
Laboratory Studies and Biopsy
There are no laboratory tests to confirm the diagnosis. A punch biopsy can provide adequate tissue for the dermatopathologist to differentiate between the different forms of epidermolysis bullosa: simplex, junctional, and dystrophic.
Erythema multiforme bullosum may have a similar appearance, but the distribution is less apt to be limited to the distal extremities.
The first appearance of the condition may be confused, with staphylococcal scalded skin syndrome (see Chapter 105, Staphylococcal Scalded Skin Syndrome).4
Management is primarily prevention of trauma, careful wound care, and treatment of complicating infections. Other supportive measures such as pain management and nutritional support are often necessary. Screening the skin for squamous cell carcinoma is important in adulthood for the dystrophic form.2
Periodic skin examinations should be done to help manage symptoms and screen for malignancy.
Avoid trauma and come in early if there are any signs of infection or malignancy.
Pityriasis Lichenoides Et Varioliformis Acuta
A young man presented with a varicelliform eruption that he has had for 6 weeks (Figure 157-6). Initially, he was diagnosed with varicella and given a course of acyclovir. Then he was misdiagnosed with scabies and treated with permethrin. A correct diagnosis of PLEVA was made by clinical appearance and confirmed with biopsy. His skin lesions cleared with oral doxycycline.
A college student with pityriasis lichenoides et varioliformis acuta. His skin lesions cleared with oral doxycycline. (Used with permission from Richard P, Usatine, MD.)
PLEVA or Mucha-Habermann disease and pityriasis lichenoides chronica are maculopapular erythematous eruptions that can occur in crops of vesicles that can become hemorrhagic over a course of weeks to months (Figures 157-7).5
There is a predilection for males in the second and third decades.
PLEVA occurs in preschool and preadolescent children as well.6
A teenager with pityriasis lichenoides et varioliformis acuta (PLEVA, Mucha-Habermann disease). (Used with permission from Weinberg SW, Prose NS, Kristal L. Color Atlas of Pediatric Dermatology, 4th edition, Figure 9-35, New York, NY: McGraw-Hill, 2008.)
Etiology and Pathophysiology
PLEVA occurs with crops of maculopapular and papulosquamous lesions that can vesiculate and form hemorrhagic vesicles (Figures 157-6 and 157-7). Although it resembles varicella, new crops of lesions continue to appear over weeks and months. It can be thought of as “chickenpox that lasts for weeks to months.”
Lesions typically occur over the anterior trunk and flexural aspects of the proximal extremities. The face is spared.
There are no specific laboratory tests for PLEVA except biopsy.
A punch biopsy is helpful in making the diagnosis. It may be necessary to differentiate PLEVA from lymphomatoid papulosis (see the following section “Differential Diagnosis”).
Varicella—A varicella direct fluorescent antibody test can confirm acute varicella. If no viral testing was done and what appeared to be varicella persists, PLEVA should be considered (Chapter 108, Chickenpox).
Pityriasis lichenoides chronica is the chronic form of PLEVA and can be distinguished from PLEVA by length of time and biopsy (Figure 157-8). It has a more low-grade clinical course than PLEVA and the lesions appear over a longer course of time.
Erythema multiforme is a hypersensitivity syndrome in which target lesions are seen. The target lesions have epidermal disruption in the center with vesicles and/or erosions. Look for the target lesions to help differentiate this from PLEVA (see Section 12, Hypersensitivity Syndromes and Drug Reactions).
Lymphomatoid papulosis presents in a manner similar to PLEVA with recurrent crops of pruritic papules at different stages of development that appear on the trunk and extremities. Although it has histologic features that suggest lymphoma, lymphomatoid papulosis alone is not fatal. It is important to differentiate this from PLEVA because these patients need to be worked up for coexisting malignancy. These patients tend to be older and a punch biopsy can make the diagnosis.
Gianotti-Crosti syndrome (papular acrodermatitis of childhood) may resemble PLEVA but the lesions are usually acral in distribution (Figure 157-9).3 The erythematous papules and vesicles are found on the extremities and sometimes on the face. It is a benign syndrome associated with many childhood viruses that may last 2 to 8 weeks.
Pityriasis lichenoides chronica is the chronic form of pityriasis lichenoides et varioliformis acuta that may persist for months to years. (Used with permission from Richard P. Usatine, MD.)
Gianotti-Crosti syndrome, “papular acrodermatitis of childhood,” in a 7-month-old child. The acral eruption started just after a viral upper respiratory infection and involved the feet, lower legs, and buttocks. (Used with permission from Richard P. Usatine, MD.)
Needed only if the disease does not resolve.
This is usually a temporary disease but if it becomes chronic there are treatments that could help such as oral macrolides or doxycycline.
A young man with a past history of diarrhea and malabsorption carries a past diagnosis of gluten-induced enteropathy. Despite a gluten-free diet he continues to have a pruritic eruption on his shoulders, back, extremities and buttocks (Figures 157-10 and 157-11). While the most likely diagnosis is dermatitis herpetiformis, a punch biopsy was performed to confirm this before starting the patient on oral dapsone.
A young man with dermatitis herpetiformis and gluten-induced enteropathy. The daily vesicles that form are fragile and rapidly become small erosions. (Used with permission from Richard P. Usatine, MD.)
Dermatitis herpetiformis that has persisted even though he is on a strict gluten-free diet. The buttocks is a commonly involved area. His gastrointestinal symptoms have resolved on the gluten-free diet but his eruption has only diminished. His skin lesions resolved with oral dapsone. (Used with permission from Richard P. Usatine, MD.)
Etiology and Pathophysiology
The disease is related to gluten and other diet-related antigens that cause the development of circulating immune complexes and their subsequent deposition in the skin. The term herpetiformis refers to the grouped vesicles that appear on extensor aspects of the extremities and trunk and is not a viral infection or related to the herpes viruses. The disease is characterized by the deposition of immunoglobulin (Ig) A along the tips of the dermal papillae. The majority of patients will also have blunting and flattening of jejunal villi, which leads to diarrhea even to the point of steatorrhea and malabsorption.
The clinical eruption is characterized by severe itching, burning, or stinging in the characteristic extensor distribution. Herpetiform vesicles and urticarial plaques may be seen. Because of the intense pruritus, characteristic lesions may be excoriated beyond recognition (Figures 157-10 to 157-12).
Dermatitis herpetiformis showing erosions from vesicles and bullae on the buttocks, legs and arms in a young girl with gluten-induced enteropathy. (Used with permission from Weinberg SW, Prose NS, Kristal L. Color Atlas of Pediatric Dermatology, 4th edition, Figure 14-32, New York, NY: McGraw-Hill, 2008.)
Classically, the lesions (or excoriations) are seen in the extensor aspects of the extremities, shoulders (Figure 157-10), lower back, and buttocks (Figures 157-11 and 157-12).
If the patient has gluten-induced enteropathy, antigliadin and antiendomysial antibodies may be present. A blood test for antigliadin antibody is a sensitive test for gluten-induced enteropathy.
Diagnosis is confirmed by a punch biopsy. It is best to biopsy new crops of lesions. A standard histologic examination will show eosinophils and microabscesses of neutrophils in the dermal papillae and subepidermal vesicles. Direct immunofluorescence reveals deposits of IgA and complement within the dermal papillae.
Scabies may have a similar appearance with pruritus, papules, and vesicles. If the lesions and distribution suggest scabies, it should be ruled out with skin scraping looking for the mite, feces, and eggs. If the scraping is negative, but the clinical appearance suggests scabies, empiric treatment with permethrin should be considered as well. If the lesions persist, consider a punch biopsy to look for dermatitis herpetiformis (Chapter 128, Scabies).
Nummular and dyshidrotic eczema may also be diagnostic considerations, but response to steroids in eczema may be helpful in differentiation (Chapter 130, Atopic Dermatitis).
With a gluten-free diet, 80 percent of patients will show improvement in the skin lesions. The degree of benefit is dependent upon the strictness of the diet.9
A gluten-free diet may help the enteropathy and decrease the subsequent development of small bowel lymphoma.
Dapsone may be necessary indefinitely.10
Follow-up is needed to control the disease and monitor nutritional status.
Nutritional counseling is important for all patients with gluten-induced enteropathy. Persons with dermatitis herpetiformis and gluten-induced, enteropathy should not eat wheat and barley but can eat rice, oats, and corn.
MJ. The clinical spectrum of epidermolysis bullosa. Br J Dermatol. 2002;146(2):267–274.
et al. Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006. J Am Acad Dermatol. 2009;60 (2):203–211.
AJ. Bullous diseases in children. In: Paller
AJ, eds. Hurwitz’s Clinical Pediatric Dermatology 3rd ed. Philadelphia, PA: Elsevier; 2006:345.
AY. Staphylococcal scalded skin syndrome: diagnosis and management. Am J Clin Dermatol. 2003;4(3):165–175.
EM. Pityriasis lichenoides and its subtypes. J Am Acad Dermatol. 2006;55(4):557–572.
et al. Pityriasis lichenoides in childhood: a retrospective review of 124 patients. J Am Acad Dermatol. 2007;56(2):205–210.
F. Pityriasis lichenoides: a clonal T-cell lymphoproliferative disorder. Hum Pathol. 2002;33(8):788–795.
C, De Panfilis
G. Medium-dose ultraviolet A1 therapy for pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica. J Am Acad Dermatol. 2002;47(3):410–414.
AGA Institute: AGA Institute Medical Position Statement on the Diagnosis and Management of Celiac Disease. Gastroenterology. 2006;131(6):1977–1980.