Section 14. Bullous, Pustular, and Ulcerating Diseases

Pemphigus vulgaris is a rare autoimmune, bullous disease that occasionally occurs during childhood. The disease affects both the skin and mucous membranes and can be life threatening. The typical lesions of pemphigus vulgaris are pictured here. Erosions of the lips, gums, tongue, and palate, as pictured in Fig. 14-1, are a common presenting symptom and may be misdiagnosed early in the course of the disease. The difficulty in chewing and swallowing that may occur can become a significant complication. Cutaneous lesions consist of flaccid weeping blisters that quickly erode to leave large denuded areas of skin. Nikolsky's sign, the extension of blistering by lateral finger pressure, is seen in the presence of widespread disease. Figure 14-2 shows the kind of crusting that develops as the roofs of blisters of pemphigus vulgaris disintegrate. Antibodies to desmoglein 1 are associated with skin lesions and antibodies to desmoglein 3 are associated with oral lesions.

The blisters of pemphigus vulgaris may arise on an erythematous base, or on normal-appearing skin, as pictured here. A variety of modalities have been employed in the treatment of this disease. The patient who is seriously ill requires hospitalization. For most patients, the most rapid and effective treatment remains high-dose systemic steroids. Patients undergoing this form of therapy are at high risk for infection and must be followed with extreme care. Immunosuppressive agents such as azathioprine, mycophenolate mofetil, and plasmapheresis are other useful therapies.

When the cutaneous changes of pemphigus take place in intertriginous spaces, clear blistering is not evident. Rather, one sees boggy inflammation and tumid granulation. The essential histologic process is again epidermal acantholysis, but blister roofs part almost at once and secondary infection is inevitable. This figure is a good representation of the kind of clinical appearance that develops in pemphigus vegetans. Lesions on other parts of the body take the form of pemphigus vulgaris.

This figure illustrates the type of scaling that accompanies pemphigus foliaceus. What one sees is largely exfoliating stratum corneum, not blisters. On biopsy analysis, one finds acantholysis occurring high in the epidermis, usually in the granular layer. There may be a subcorneal cleft, but the rest of the epidermis remains attached. Antibodies to desmoglein-1 are associated with pemphigus foliaceous.

This form of pemphigus is less severe than pemphigus vulgaris because blister formation occurs higher in the epidermis. As a result, there is less compromise of vital cutaneous functions. In most areas of the world, pemphigus foliaceus is extremely unusual in children. In Brazil, there is an endemic form of pemphigus foliaceus, termed fogo selvagem, which affects individuals of all ages. Pictured here are the typical lesions of pemphigus foliaceus. The disease often begins in the scalp with areas of erythema and scaling. As it progresses to involve the trunk and extremities, there evolve numerous crusting and erythematous plaques. Severe scaling is common, but usually there is no blister formation and no involvement of the oral cavity. Treatment consists of topical or systemic steroids, depending on the severity of the disease.

Lesions in the perioral area, as seen in this figure, are quite common. Oral mucosal involvement is less common, in contrast to pemphigus vulgaris. Often, patients with pemphigus foliaceus are initially thought to have recurrent impetigo, although the infection does not totally clear with appropriate antibiotics. It is important to realize that secondary infection often occurs in these patients, and this should be considered when patients have flare-ups or the disease is difficult to control.

This figure shows annular lesions that are seen in childhood forms of pemphigus foliaceus. Direct immunofluorescence is important in making the diagnosis. In addition, antibodies to desmoglein, an epidermal desmosomal component, have been found. Treatment consists of topical or systemic steroids, depending on the severity of the disease.

This is the least serious form of the pemphigus group of diseases and is probably best considered as a localized form of pemphigus foliaceus. It is unusual in children but does occur occasionally. Typically, there is scaling and crusting in a “butterfly distribution” on the face, as well as involvement of the chest, back, and scalp. The disease may be mistaken for severe seborrheic dermatitis or systemic lupus erythematosus. Biopsy analysis of a lesion of pemphigus erythematosus reveals an intraepidermal bulla in the upper layers of the epidermis. As in all forms of pemphigus, IgG antibody to intercellular substance is present in the serum. Pemphigus erythematosus tends not to be a severe disease; most cases can be controlled with topical steroids alone.

This autoimmune blistering disorder is extremely rare during childhood. Tense blisters can arise on either erythematous or normal skin and may be pruritic. Lesions tend to cluster and may be preceded by the development of urticarial plaques. Sites of predilection include the face, groin, and inner thighs. Palm and sole involvement is sometimes seen in children, and mouth lesions are extremely unusual. Blisters generally heal without scarring but may leave temporary hyper- or hypopigmentation. The prognosis is generally good.

This condition is most common during adulthood, but it does occur in children. Characteristically, crops of vesicles and pustules (Fig. 14-13) spring up and evolve into areas of superficial crusts and scales. As the lesions coalesce, they form the type of arcuate plaque that is illustrated in Fig. 14-14. The most common locations are the axillae, groin, and flexures of the upper and lower extremities. The lesions are often pruritic, and, especially in childhood, there may be fever and an elevated white blood count. The etiology of this condition is completely unknown. Diagnosis is best confirmed by classic histologic appearance, which consists of collections of neutrophils just beneath the stratum corneum. The disease process is essentially benign, but dapsone is an effective therapy for the patient with frequent or severe recurrences.

This blistering disease is inherited in autosomal dominant fashion. Onset tends to occur during late adolescence. Patients with this disorder have a pruritic vesicular eruption in intertriginous areas that is worse during the summer months. Intact bullae may be absent, and often there is only an erosive and crusted intertrigo in the axillae, in the groin, and on the neck. Control of this condition is best achieved by the avoidance of the causative factor, such as heat or friction, and the treatment of superinfection when it occurs.

This autosomal dominant condition is among the mildest of the diseases that are termed epidermolysis bullosa. The defect in most cases of epidermolysis bullosa simplex is due to mutations of the genes coding for keratins 5 and 14. Epidermolysis bullosa simplex begins at birth or in early infancy, and throughout life the site of blistering corresponds to areas of friction or other trauma. During infancy, blisters occur on the neck, lower extremities, and hands and feet. In the child who is old enough to wear shoes, the dorsa of the toes are a common site of bulla formation.

In this condition, cleavage occurs through the basal cell layer of the epidermis, and the dermoepidermal junction is otherwise undisturbed. The result is that the lesions are superficial in appearance, and cutaneous function is well preserved. The lesions of epidermolysis bullosa simplex tend to heal without scarring. In children with this disorder, mucous membrane involvement is minimal and usually does not produce serious difficulty. There may be some nail dystrophy, but this also heals with the cutaneous process.

This particular variant of epidermolysis bullosa involves only the hands and feet; the cleavage plane is above the basal layer. The lesions tend to appear first during late childhood and adolescence. Pictured here are blisters on and near the great toe; the appearance of the bullae is modified by the thickness of the stratum corneum in this area. Patients with this disease tend also to suffer from hyperhidrosis. Minimizing trauma to the hands and feet and the use of antiperspirants help to prevent blister formation.

This form of epidermolysis bullosa is characterized by grouped, herpetiform blistering that generally occurs on the trunk but is also seen on the face and extremities. Blistering in infancy is often severe and extensive. After a few months, infants develop frequent blistering of the palms and soles. This disorder is associated with a defect in keratin 5 genes that causes clumping of tonofilaments in epidermal basal cells.

This autosomal recessive disorder is due to mutations in genes that allow binding of the basal keratinocytes to the lamina densa. It is now widely believed that there are three types of junctional EB. The Herlitz type presents with blisters at birth (Fig. 14-21), or developing during the first few days of life. Although there is little scarring, the blisters tend to evolve into chronic nonhealing erosions. These tend to be most severe around the nose and mouth (Fig. 14-20), and it is not unusual for excessive granulation tissue to cause obstruction of the nares. Scalp erosions and chronic paronychia with nail loss are also common. Non-Herlitz EB, the second type, is clinically similar, but in most cases, there is less formation of granulation tissue. The third type of junctional EB is a rare form that is associated with pyloric atresia.

There is no specific treatment, and emphasis must be placed on pain control, appropriate dressings for the blisters and chronic ulcerations, and management of the malnutrition and anemia that tend to accompany this disease. The prognosis varies according to disease severity, but, in the Herlitz form, there is a high rate of mortality during early childhood. A severe case is shown in Fig. 14-22.

The autosomal recessive, dystrophic form of epidermolysis bullosa is a multisystem disease that is characterized by chronic and recurrent subepidermal blistering. The disorder often leads to severe disability, interfering with the normal processes of growth and development. Blister formation usually begins at or shortly after birth, and intraoral involvement may lead to early feeding difficulties. Normal handling of the infant with this disease results in the formation of tense bullae which quickly evolve into ulcerations. The typical blisters, crusts, and erosions of dystrophic epidermolysis bullosa are seen in Fig. 14-23. The most serious sequelae of this disorder are due to the fact that the blisters heal with scarring. The recurrent episodes of bulla formation and healing on the hands and feet may result in an acquired syndactyly, as illustrated in Fig. 14-24. In the esophagus, the same process eventuates in mechanical obstruction. The strictures that form lead to nutritional difficulties and even perforation or squamous cell carcinoma of the esophagus. Eye involvement, with ulcers, keratitis, and opacities, is an additional problem.

This figure shows a foot with complete destruction of the toenails, induced syndactyly of the fourth and fifth toes, and typical wrinkled scarring of the skin surface. Appropriate care for the child with epidermolysis bullosa must begin in the nursery and involves the use of topical dressings to protect eroded skin and the careful handling of the infant to avoid new blister formation. Subsequent management includes efforts to minimize skin trauma, good dental and ophthalmic care, and careful attention to diet and nutrition.

This is a dystrophic form of epidermolysis bullosa that is inherited in autosomal dominant fashion. Widespread blistering may be present at birth. During puberty, patients with this disorder develop distinctive ivory-white follicular papules on the chest and lower back. The albopapuloid form of epidermolysis bullosa has been associated with a defect in anchoring fibrils. The prognosis tends to be good.

This figure illustrates another patient with a dominant form of scarring epidermolysis bullosa. The Cockayne-Touraine form tends to begin during infancy and is associated with widespread blistering and milia formation. Shown here are a number of tense bullae on the flexor surface of the arm. Mouth involvement and nail dystrophy may also occur.

This is a distinct blistering disease that occurs exclusively during childhood, most commonly during the first 5 years of life. The disorder is characterized by large, tense bullae that tend to occur in the genital area, lower abdomen and back, and lower extremities. The degree of pruritus is variable. Figure 14-28 illustrates the particular fashion in which the blisters tend to cluster. Note the circular or oval configuration of blisters. As an early lesion heals with crusting and hyperpigmentation, new lesions arise in a string-of-pearls or rosette-like pattern along the periphery. The blisters themselves may be elongated or sausage-shaped. Figure 14-29 shows the clustering of tense blisters on the inner thighs. This is probably the most common location for chronic bullous dermatosis of childhood.

These two figures show the annular and polycyclic clustering of blisters that is so typical of this disorder. Biopsy of a lesion reveals a subepidermal blister with an infiltrate of neutrophils and/or eosinophils. Immunofluorescence is more distinctive and usually shows a linear deposit of IgA along the basement membrane (in the lamina lucida). In most patients, there are also circulating IgA antibodies directed against the basement membrane. For most affected children this is a self-limited disease and it resolves spontaneously over a period of several years. Sulfapyridine and dapsone are the most effective therapies. These drugs have hemolytic activity, and the patients must be monitored for induced anemia and methemoglobinemia. A test for adequate glucose-6-phosphate dehydrogenase should be done before initiation of therapy, and hemoglobin determinations should be made subsequently until stabilization occurs.

This intensely pruritic papulovesicular eruption is fairly unusual during childhood. Figure 14-32 shows the symmetrical distribution of the grouped, excoriated lesions on the extensor extremities and buttocks. Additional papules and vesicles on the upper chest and face are seen in Fig. 14-33. Dermatitis herpetiformis is a disease that affects both the skin and the gastrointestinal tract. The majority of children with this disorder have a gluten-sensitive enteropathy. This may lead to diarrhea and malabsorption, or it may be evidenced only by villous atrophy on jejunal biopsy analysis. The approaches to treatment of this disease include sulfapyridine or dapsone and a gluten-free diet. As mentioned above, children treated with dapsone or sulfapyridine must be carefully monitored for the development of hemolytic anemia. Adherence to a diet that contains no gluten is extremely difficult but, if accomplished, will often lead to prolonged remission.

This picture of lesions of dermatitis herpetiformis shows them in a highly characteristic distribution on the back. Because of the intense pruritus, excoriations tend to outnumber the primary papulovesicles. Direct immunofluorescence of perilesional skin is an effective means of confirming the diagnosis of dermatitis herpetiformis. Typically, there are granular deposits of IgA at the tips of the dermal papillae.