Section 13. Urticarial, Purpuric, and Vascular Reactions

A wheal is an edematous papule that may enlarge to form a pink, sharply circumscribed, elevated plaque. The typical lesions of urticaria, pictured here, have a suggestion of central clearing. By definition, the individual lesions of urticaria evolve quickly and resolve within 24–48 hours. They are usually accompanied by severe pruritus. The most common etiologies of urticaria are medications, foods, and viral (Fig. 13-2) and bacterial infections. Autoimmune disease and malignancy are extremely rare causes. In the child with chronic urticaria, it is often difficult or impossible to identify a single cause.

This type of urticaria is causally related to elevation in body temperature and sweating. The lesions usually develop rapidly after the beginning of exercise and resolve rapidly and spontaneously with cooling. The urticaria that develops in this condition has a typical appearance, illustrated here. The lesions consist of red or flesh-colored papules 2–3 mm in diameter that are surrounded by an ill-defined erythematous macule. The use of antihistamines will decrease the frequency and severity of attacks. Doxepin may also be effective.

There are urticarias in which stroking, pressure, cold, heat, or sun exposure are causative. Figure 13-4 is whealing in linear form produced by stroking the skin with a degree of force that would ordinarily cause nothing more than transient erythema. The phenomenon, called dermographism, is present in a small percentage of normal individuals. Figure 13-5 is a huge wheal produced by resting an ice cube on the forearm. Cold-induced urticaria may be acquired or inherited. In the most common, acquired form, patients develop lesions shortly after ingesting cold foods or liquids or shortly after exposure to a drop in environmental temperature. Patients with this form of sensitivity are at risk for laryngeal edema or circulatory collapse as a result of significant cold exposure. Antihistamines or doxepin is of some help in preventing attacks. In a very rare syndrome, contact of the skin with water, without respect to its temperature, produces wheals (aquagenic urticaria).

This disorder is termed multiforme because the morphology of its lesions is so variable. Figure 13-6 is an overview of a severe case. The primary lesion is most often an erythematous macule that evolves into a papule. Early in the course, these lesions may easily be mistaken for urticaria. As the lesions enlarge, they form round or irregularly shaped plaques. The central area may blister or become dusky in color; this change represents the necrosis of keratinocytes in areas of active involvement (Fig. 13-7).

Concentric circles of erythema and dark gray discoloration may evolve, forming the typical “target” lesion of erythema multiforme. The “target” lesions may coalesce and develop annular or serpiginous borders. Figure 13-8 is a close-up of the target-like quality of the variably sized and shaped plaques. Note the redness and edema at the border and the duskier appearance at the center. Erythema multiforme tends to be acral in distribution, and the dorsum of the hand is a particularly common location (Fig. 13-9).

The type of bulla that may occur in erythema multiforme is shown here. Mucosal lesions are not uncommon. Erythema multiforme is a self-healing disease, with an average duration of about 2 weeks. Herpes simplex infection is by far the most common etiologic agent. Finally, a wide variety of drugs, most commonly the sulfonamides, may cause this syndrome.

Drugs are the major etiologic factor in the development of erythema multiforme major. The most common agents are sulfonamides, anticonvulsants, and nonsteroidal anti-inflammatory drugs. Mycoplasma pneumoniae has been implicated as the most commonly associated infectious agent. The cutaneous lesions include fixed erythematous macules, target lesions, and bullae. There may be progression to widespread erythema and denudation, leaving underlying erosions (Fig. 13-11). At least two mucous membranes are involved in this syndrome. The oral cavity is almost always involved, with bullae, ulcerations, and crusting most commonly presenting on the lips, buccal mucosa, and palate (Fig. 13-12). The bulbar conjunctiva and anogenital mucosa may also be involved. Tracheal and bronchial involvement may result in breathing difficulty. Ocular involvement may result in scarring of the conjunctivae or corneas.

This is a severe generalized eruption that is almost always the result of a reaction to a medication. The most common agents are sulfonamides, anticonvulsants, and nonsteroidal anti-inflammatory drugs. Combinations of bullae and erosions are seen; the bullae occur especially on or around the lips, in the mouth, and on other mucous surfaces. Frozen section processing of a biopsy specimen of toxic epidermal necrolysis allows for rapid diagnosis. In patients with erosions and blisters, one sees necrotic keratinocytes, severe degeneration of the basal layer, and a subepidermal separation.

Note the extensive involvement with large and small bullous lesions. The mortality rate in this disease is significant; most deaths are related to superinfection and sepsis. Patients with toxic epidermal necrolysis benefit enormously from intensive medical care, in a burn unit when possible. The role of systemic steroids in this disease remains extremely controversial.

This is a rare skin disease that is characterized by purple or yellowish papules, nodules, and plaques that tend to cluster on the hands, feet, and extensor surfaces of the extremities. The skin overlying joints is a favored location. The distribution is usually symmetrical, and the disease tends to be chronic. Lesions of erythema elevatum diutinum may be asymptomatic but in some cases are painful. Figure 13-16 shows typical nodules and plaques on the elbow, and yellowish papules on the finger are seen in Fig. 13-17. The etiology of this chronic leukocytoclastic vasculitis remains unknown, but an immune complex etiology has been suggested. Dapsone is one mode of treatment.

This syndrome is characterized by painful, raised, erythematous plaques and nodules. The cutaneous eruption is accompanied by spiking fevers and a neutrophilic leukocytosis. This condition is seen most commonly in middle-aged women, but it does occur in children. Skin biopsy reveals a widespread infiltrate of polymorphonuclear leukocytes throughout the dermis. Sweet's syndrome is often associated with either malignancy or antecedent infection. Systemic corticosteroids are the treatment of choice.

This is an erythematous and edematous lesion that gradually enlarges to form annular, polycyclic, and gyrate shapes. The lesions tend to resolve spontaneously but may reappear. Erythema annulare centrifugum has been attributed to a wide variety of causes. In some cases, it is temporally related to the development of malignancy and resolves with treatment or removal of the tumor. In other patients, the disease has been related to superficial fungal infections and a wide variety of viral and bacterial diseases.

Twins who develop with some form of common circulation in utero may show a temporary difference of cutaneous color related to oddities of hemodynamics. In the figure, one sees twin neonates, of whom the one on the right is uniformly and abnormally erythematous, whereas the other is abnormally pallid. The one looks plethoric, the other, anemic. In the course of time, restoration of normal blood counts and color will develop in both.

The word harlequin connotes, among other things, the quality of being parti-colored. Here we see an infant in whom the left half of the trunk is pale and the right half red. The anomaly is transient and depends on circulatory derangement by gravity. If this child were to be turned onto its left side, which is now pale, that side would become red and the right side, now red, would become pale. This phenomenon is much more common among preterm infants.

Hemorrhage into the skin takes many forms in structure, shape, and color. What we generally designate as purpura are macular lesions that may be punctate (petechial) or diffuse and red purple in color (ecchymotic). The causes are numerous. Most common among the benign pigmented purpuras is Schamberg's disease, a disorder of unknown etiology. Affected children have numerous discrete patches of petechiae on the lower extremities (Figs. 13-22 and 13-23). The individual lesions evolve into typical brown-orange macules containing “cayenne pepper” spots. Fresh petechiae occur at other sites. More significant causes of purpura include septicemia (see Figs. 15-36, 15-37, 15-38, 15-39), a wide variety of hematologic disorders, and vasculitis. Palpable purpura is, in fact, the hallmark of leukocytoclastic vasculitis, which may be a manifestation of bacterial or viral infection, drug allergy, connective tissue disease, or cryoglobulinemia. Henoch-Schönlein purpura, a common cause of childhood leukocytoclastic vasculitis, is discussed in Figs. 13-30, 13-31, 13-32.

This is a group of chronic diseases of unknown etiology characterized by extravasation of erythrocytes into the skin resulting in a clinical picture of petechiae and a golden brown discoloration due to hemosiderin deposition. Lichen aureus is a localized form more commonly seen in children and young adults consisting of a solitary or localized group of lesions that is more frequently seen on the leg although any part of the body may be involved. Figure 13-24 shows an earlier, more hemorrhagic appearing lesion, whereas in Fig. 13-25 a more golden color is observed with only few petechiae noted.

These figures show hemorrhage into the skin occasioned by difficult passage of newborns through the birth canal. Such events are common, and as long as the hemorrhage is into skin alone, no great or lasting harm results. In Fig. 13-26, one sees edema and ecchymosis that resulted from molding of the head in a prolonged but spontaneous delivery. Figure 13-27 shows a cephalhematoma of considerable size from a similar event. Modern obstetrics, which encompasses prenatal study of the maternal pelvis, ultrasonography, sedation, muscle relaxants, anesthesia during delivery, and cesarean section when indicated, has tended to make serious traumatic purpura of this sort less common. Nevertheless, in severe cases of traumatic hemorrhage of this kind, imaging studies for the possibility of skull fracture are good practice.

Throughout life, hard knocks in the physical sense are the lot of us all. Rupture of capillaries is thus exceedingly common, and more extensive rupture of arterioles, venules, arteries, or veins is common enough. Petechiae, ecchymoses, vibices, and hematomas are banal, nearly everyday events. The black eye and contusions are of everyone's experience. Illustrated here is a traumatic ecchymosis that may well represent a hickey (“passion purpura”).

This condition is a rare and exceedingly serious consequence of certain acute infectious diseases. Scarlet fever of bygone days, meningococcal meningitis, severe varicella, and congenital protein C deficiency have been known to be complicated by fulminating purpura that went on to gangrene, extreme toxicity, shock, and death. The cause of the condition seems to be necrotizing vasculitis attended by defects of clotting (disseminated intravascular coagulation).

Palpable purpura is but one aspect of a syndrome that is also marked by attacks of arthralgia, abdominal pain, and hematuria. The entire complex of visible cutaneous purpura, arthralgia, and visceral signs and symptoms results from a widespread IgA-related vasculitis. In addition to purpura, as shown in Fig. 13-30 on the buttocks and in Fig. 13-31 around an ankle, the skin may show edematous plaques, vesicles, and even necrosis. Without the cutaneous signs, arthralgia might mislead one to consider rheumatic fever; abdominal pain might suggest an acute surgical abdomen and lead to unnecessary laparotomy, and hematuria might mislead to diagnoses like glomerulonephritis or nephrolithiasis. Good clinical judgment, however, will confirm the diagnosis of Henoch-Schönlein purpura. The cause of this condition is not known. The prognosis is usually good, except for the rare child who goes on to develop chronic nephritis.

This picture is a good representation of both the purpuric elements and the edema that may appear in the Henoch-Schönlein syndrome. In itself, without signs and symptoms of hemorrhagic consequences or edema in joints, gut, or kidneys, many other diagnoses would have to be differentially considered in an appearance like this.

This striking disorder occurs in infants between 4 months and 2 years of age. The sharply circumscribed lesions favor the extremities and are edematous, ecchymotic, and purpuric. Edema of the ears and eyelids may also be noted. Biopsy of an active lesion reveals an intense leukocytoclastic vasculitis. However, in contrast to Henoch-Schönlein purpura, systemic symptoms are very rare. There may be several outbreaks of new lesions, but the entire process generally resolves in approximately 2 weeks.

This autoimmune condition is triggered by causes unknown and is manifest by intracutaneous bleeding. The purpura takes the form of petechiae and ecchymoses not only in the skin, where it is obvious, but also in the oropharyngeal mucous membranes, the nose, and the gastrointestinal tract. The illustration here is of ecchymosis in the pinna of an ear.

This very common condition is characterized by recurrent episodes of painful ulceration on the lip, tongue, or buccal surfaces. The individual lesions quickly evolve from erythematous macules to papules and then to yellowish ulcerations with a surrounding pink or red halo. The etiology is not known, and the ulcers heal in 7–10 days without scarring. Whereas a solitary lesion is the cause of only temporary, minor discomfort, there are some individuals who develop deeper and larger ulcers or numerous erosions. For them, aphthous stomatitis can be a severe problem.

This rare disease is characterized by a classic triad of recurrent ulcerations of the oral mucosa, genital ulcers, and eye involvement. The oral ulcers, one of which is pictured here, tend to be larger, more numerous, and more frequently recurrent than those of simple aphthous stomatitis. Genital lesions occur on the penis and scrotum in males, and on the vulva in females. These frequently recurrent ulcers tend to heal with scarring. The various forms of eye involvement include uveitis and keratoconjunctivitis and may eventuate in blindness.

The sharply marginated oral ulcers of this syndrome are pictured in Fig. 13-38. Figure 13-39 shows the typical genital lesions. Other cutaneous lesions may be widespread and include papules, vesicles, abscesses, and lesions of erythema nodosum. In addition to the eyes and skin, a number of other organ systems may become involved. Severe chronic arthritis and thrombophlebitis are common occurrences. Gastrointestinal disease ranges from mild abdominal discomfort to chronic diarrhea and an ulcerative colitis-like illness. Neurologic manifestations, including recurrent meningoencephalitis and brain stem lesions, are often the most serious and can be life threatening. Diagnosis of Behçet's syndrome is based on the presence of the typical clinical findings. The disease is difficult to treat, but colchicine, immunosuppressive drugs, and corticosteroids are the most frequently used therapies.

This disorder results from prolonged and repeated exposure to infrared radiation. Historically, and before the advent of central heating, erythema ab igne was seen on the legs of individuals who sat or stood in front of heating devices. In this era, more common causes are hot water bottles and heating pads. The patient in Fig. 13-40 used a heating pad for relief from menstrual cramps; the patient in Fig. 13-41 applied heat to his thigh after an injury. These typical lesions are characterized by reticular erythema and brownish pigmentation. Epidermal atrophy and subepidermal blisters may also occur.