Section 15. Cutaneous Manifestations of Systemic Disease

Figure 15-1 illustrates cutaneous involvement of systemic lupus erythematosus (SLE) in the classic butterfly pattern on the face. This macular and intensely erythematous eruption is frequently aggravated by sun exposure and may flare with other symptoms of systemic disease. Figure 15-2 shows the temporary alopecia that is also a hallmark of SLE. This autoimmune disease of unknown etiology affects almost every organ system. The most common findings in the child with SLE are fever, arthralgias, and arthritis. In addition, pleuritis, pericarditis, and central nervous system involvement are frequently seen in children with SLE. Lupus nephritis develops in the vast majority of affected children and may eventually cause renal failure.

These figures illustrate additional cutaneous features of SLE. The lesions on the back (Fig. 15-3) and the hands (Fig. 15-4) are intensely erythematous macules and slightly edematous papules and plaques. Childhood SLE occurs most frequently during adolescence and is more common among African Americans and among girls. The diagnosis is established when four of eleven clinical and laboratory criteria are met. Clinical criteria include rash (either malar or discoid), photosensitivity, oral ulcers, and disease of the joints, lungs, kidneys, and central nervous system. The single most reliable laboratory test is antinuclear antibody which will be positive in almost every case of childhood SLE. Other laboratory criteria include leukopenia, thrombocytopenia, and the presence of antinative DNA antibodies.

This condition is due to the transplacental passage mainly of anti-Ro (anti-SS-A) antibodies from mother to infant. However, anti-La (anti-SS-B) and anti-RNP antibodies may be implicated. The mother may suffer from a form of connective tissue disease or may be completely asymptomatic. The infants pictured in Figs. 15-5, 15-6, 15-7 were born with these atrophic and telangiectatic plaques on the face. The lesions may also resemble those of subacute cutaneous lupus in the older patient. The skin lesions, which are slightly more common in girls, tend to resolve without scarring. Nonfluorinated topical steroids and avoidance of the sun are the only treatments that may be required.

Figure 15-8 shows atrophic telangiectatic changes that are most often seen on the temple and scalp which may lead to permanent alopecia. A frequent complication of neonatal lupus is congenital heart block that may be found in utero. This situation is potentially life threatening and may sometimes require implantation of a pacemaker. Although neonatal lupus is self-limited, there are reports of affected infants going on to develop connective tissue disease during adolescence.

Illustrated here is the characteristic plaque of a discoid lesion of lupus erythematosus. There is a violaceous hue at the border and central atrophy with scarring. Similar involvement in the scalp can cause permanent alopecia. Discoid lesions may be a cutaneous manifestation of SLE or the sole physical finding in a disease that does not go on to affect any other organ system. Treatment consists of avoidance of the sun or the use of sunscreens, antimalarial agents, and topical or intralesional corticosteroids.

This collagen vascular disease is characterized by a combination of symmetrical proximal upper and lower extremity muscle weakness and cutaneous disease. Early symptoms of muscle involvement include general malaise, difficulty in playing or climbing stairs, myalgias, and muscle tenderness. These illustrations are highly characteristic of the cutaneous part of the syndrome. Figure 15-11 shows symmetrical, intense erythema and edema of the face. The violaceous color of the periorbital rash is sometimes described as heliotrope in hue; the edema is so intense that it makes the face look puffy. Erythematous and edematous papules and plaques may also be present on the dorsum of the hand (Fig. 15-12) and on the elbows and knees. The lesions that occur over the distal interphalangeal joints are referred to as Gottron's papules. An additional cutaneous finding, which is particularly characteristic of childhood dermatomyositis, is calcinosis cutis. This may present as firm, superficial nodules or plaques or as painful deposits of calcium in muscle or fascia. Psoriasiform dermatitis of the scalp may also occur.

These illustrations show more of the cutaneous manifestations of dermatomyositis. Figure 15-13 again shows the classic Gottron's papules, and in Fig. 15-14, there is a nearly identical process on and around the elbow. In both these pictures, the cutaneous disease has advanced to wrinkling and atrophy. The diagnosis of dermatomyositis is usually made on the basis of elevated muscle enzymes (especially creatinine phosphokinase and aldolase), MRI, and muscle biopsy if necessary. Skin biopsy tends not to be helpful in differentiating dermatomyositis from other collagen vascular disease. Early therapy with systemic corticosteroids is vital in the treatment of both muscular and cutaneous disease and in the prevention of calcinosis. In contrast to the adult form of the disease, childhood dermatomyositis is not associated with malignancy.

This is a multisystem connective tissue disease that is relatively rare in childhood. Patients may suffer from arthritis and muscle weakness and from the results of pulmonary, esophageal, cardiac, and renal involvement. The condition of the skin on the face and hands is shown in Fig. 15-15. The induration and hidebound quality are hard to capture in photography but they can be imagined from the fixed expression in the face, from the exposure of the teeth by the indurated lips, and, on the hands, from the pallor of the knuckles and seeming inflexibility of the fingers. The chest may appear hidebound from the outline of the ribs and its general shape. Figure 15-16 shows scleroderma on a leg and a foot, the latter also scarred from ulceration. Again, photography cannot bring out the hardness of the skin as palpation can.

This figure of fingertips shows the pallor of Raynaud's phenomenon and telangiectasia. The patient also has scleroderma of the hands, forearms, and face. If calcinosis cutis were present or supervened, this type of case would be designated as the CREST syndrome, that is, marked by calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia. Such a combination is the most severe of the cutaneous possibilities of progressive systemic sclerosis.

Erythema marginatum is a specific cutaneous expression of rheumatic fever. An unusually good representation of erythema marginatum at a static moment is shown in Fig. 15-18. As the term indicates, the condition is redness in the form of margination. What is not told is that the red margination is around normal-appearing skin and that it is transient and recurrent over days and weeks and may precede cardiac or joint symptoms or signs. Rheumatoid arthritis sometimes has a cutaneous expression that is of the nature of urticarial dermographism or edematous erythema provoked by scratching, especially during a febrile period of the illness. Figure 15-19 provides an illustration of this, showing persistent and transient stripes of erythema and edema on the back and buttocks.

This multisystem disease is a form of necrotizing vasculitis that affects small and medium-sized arteries. Frequent areas of systemic involvement are the gastrointestinal tract and kidneys. Palpable purpura is the most common cutaneous manifestation of this disease. In addition, there may be necrotic ulcers and distal gangrene. Tender cutaneous nodules, which may be transient, are occasionally seen (Fig. 15-20), but these are more characteristic of benign cutaneous periarteritis nodosa, which has no systemic manifestations. A livedo reticularis pattern is often seen in this condition (Fig. 15-21).

This is an X-linked recessive disorder with a defective respiratory burst in neutrophils characterized by recurrent dermatitis, abscesses, and subacute suppurative lymphadenitis. Bone changes and repeated infections involving skin, lung, and liver may be seen. The neutrophils' inability to produce hydrogen peroxide and to kill bacteria can be verified by the nitroblue tetrazolium slide test. Pneumonia, meningitis, and septicemia are among the most serious complications of this disease.

This is a disease of unknown etiology that is characterized by the formation of noncaseating granulomas in many different organ systems. Sarcoidosis is more common among African Americans. It is unusual in children but it does occur. During childhood, the most common presenting signs and symptoms are lymphadenopathy, uveitis, and cutaneous disease. In very young children, arthritis, eye disease, and skin disease tend to predominate. Children with sarcoidosis may also have weight loss, fever, and respiratory involvement. Disorders of calcium metabolism are evidenced by hypercalcemia and hypercalciuria. These figures illustrate the erythematous and flesh-colored papules that may be the sole cutaneous manifestation of sarcoidosis. Systemic steroids remain the treatment of choice in this disease.

Illustrated here are highly characteristic papules of sarcoidosis on and around the eyelids. Similar lesions are common around the nose and mouth. Sarcoidosis such as this may be cutaneous only, or, more likely, may involve other organs. Investigation for systemic disease should include x-rays of the lungs and pulmonary function tests. The eyes should be examined for uveitis and lacrimal gland enlargement.

This chronic inflammatory bowel disease has several cutaneous manifestations. Most common are perianal fissures, fistulas, and granulomatous nodules. The exophytic lesions pictured here could easily be confused with condylomata acuminata. Metastatic Crohn's disease may present with ulcerations in intertriginous folds. Children with Crohn's disease may also suffer from erythema nodosum and aphthous ulcers.

The homozygous form of thalassemia (thalassemia major, Cooley's anemia) presents with a severe hemolytic anemia during infancy or early childhood. Affected children are usually small for their age and have distinctive frontal bossing along with jaundice and hepatosplenomegaly. Illustrated here are the chronic leg ulcers that are fairly common in this hematologic disorder.

Leg ulcers, commonly around the malleoli, are a frequent manifestation of sickle cell anemia. In size, shape, and appearance they are very similar to stasis ulcers. The occurrence of leg ulcers in sickle cell anemia is due to sludging of the sickled cells, local ischemia, and stasis. Treatment consists of bed rest, occlusive or semiocclusive dressings, and the use of topical and oral antibiotics when superinfection is present. Oral zinc therapy may be of value.

This form of gradually enlarging necrotic ulceration usually involves the distal lower extremity. Typical characteristics include a purulent base and a purplish undermined border. Etiologies include inflammatory bowel disease, chronic active hepatitis, and Behçet's syndrome. Arthritis may be an associated finding. Treatment consists of bed rest, local care, and the injection of intralesional steroids along the border of the lesion. Oral corticosteroids, cyclosporin A, dapsone, mycophenolate mofetil, and azathioprine are additional therapies.

This childhood disease of unknown etiology is officially diagnosed by the presence of high fever lasting for 5 or more days, and four of the following criteria: conjunctival injection (Fig. 15-30), mucous membrane changes, erythema or edema of the palms and soles (Fig. 15-31), rash (Fig. 15-32), and cervical lymphadenopathy. Perineal erythema is frequently the initial site of involvement and usually the earliest site of desquamation (Fig. 15-33). A common cutaneous finding during the second week of the illness is desquamation of the palms and soles beginning around the distal portion of the digits and then extending upward. Systemic aspects of Kawasaki disease include arthritis, aseptic meningitis, and hydrops of the gallbladder.

Coronary artery aneurysms develop in 20 percent of patients who are not treated, and some children go on to develop myocardial infarction. Current therapy, consisting of aspirin and intravenous gamma globulin, seems to reduce the incidence of cardiac disease. Children who do not meet the strict diagnostic criteria for Kawasaki disease should be treated as if they did, if there is a strong clinical suspicion. All children with Kawasaki disease should be followed with serial two-dimensional echocardiography.

This condition has some resemblance to granuloma annulare, more histopathological than clinical, but the two conditions are far from being the same. For one thing, the lesions of necrobiosis lipoidica are generally much larger than those of granuloma annulare. (The lesions in Fig. 15-34 are exceptional, probably because the disease is in early development; Fig. 15-35 is more typical for size.) The border is not ringed with papules, and the center, unlike that in granuloma annulare, is eventually atrophied or scarred. Ulceration may occur. Necrobiosis lipoidica does not abate spontaneously or with reasonable treatment to the point of restitutio ad integrum as granuloma annulare does. The condition is common in diabetes mellitus, in which case it is distinguished by addition of the term diabeticorum. Occasionally it is seen in patients who themselves do not have diabetes, but often those patients have familial histories of consanguineous relatives with diabetes mellitus.

Sepsis caused by Pseudomonas aeruginosa occurs most commonly in the child with an underlying illness. It is seen in children with immune deficiency due to cancer chemotherapy, in those with malnutrition, and in those with extensive burns. Some of the less specific cutaneous manifestations, specifically erythematous macules and petechiae, are pictured in Figs. 15-36 and 15-37. Pseudomonas sepsis may also present with discrete small nodules and bullae. The classic skin lesion of Pseudomonas sepsis is termed ecthyma gangrenosum. This form characteristically progresses quickly from a well-circumscribed area of edema to a centrally located blister and then to a gangrenous ulcer with a gray eschar. Multiple lesions in different stages of evolution may be present, and the lesions may appear on any body surface. Gram stain and culture of tissue scraped from the base of a blister will be positive for Pseudomonas.

The early treatment of meningococcemia with appropriate parenteral antibiotics can often be lifesaving. Cutaneous manifestations of this disease may provide the single most important diagnostic clue in the acutely ill child. The most common findings on the skin are petechiae and purpuras. The small petechial lesion pictured in Fig. 15-38 develops early in the course of the disease, and a scraping yields gram-negative diplococci on both Gram stain and culture. Subsequently, the lesions arise in additional crops, enlarge, and coalesce. The numerous ecchymoses pictured in Fig. 15-39 are the result of this rapidly ongoing process. These areas may become necrotic and develop eschars. Other cutaneous manifestations, occurring subsequently, include peripheral gangrene and purpura fulminans, with confluent areas of necrosis of the skin. These are the result of vasospasm, shock, and a consumption coagulopathy. A deficiency in protein C may play a particular role in this process.

Infection with Neisseria gonorrhoeae may manifest as a purulent conjunctivitis in the newborn or as a genital discharge in the sexually abused child or sexually active adolescent. Disseminated gonococcal infection, as illustrated here, is quite rare. Gonococcemia presents with a migratory polyarthralgia or septic arthritis and fever. The skin lesions are few, are often located on extremities, and may overlie the involved joints. Initially, there are small erythematous macules that progress to papules. These tender lesions may develop a small vesicle and then a gray, umbilicated center. Rarely, bullae, petechiae, and larger hemorrhagic lesions are also seen. The two figures show the macules and necrotic papules that are typical of disseminated gonococcal infection.

Mucocutaneous lesions are common in subacute bacterial endocarditis. The erythematous and hemorrhagic macules shown here are termed Janeway lesions. They may occur on the distal finger pads, palms, or soles. Other manifestations of this disease include petechiae on the oral mucosa and skin and splinter hemorrhage under the nails. Large, painful nodules or areas of gangrene involving the fingers or toes are signs of embolus formation.

The infant pictured here has a severe generalized erythroderma with diffuse scaling. In the past, the term “Leiner's disease” was used to describe children with severe and widespread seborrheic dermatitis-like eruptions, diarrhea, failure to thrive, and recurrent infections. The clinical presentation, which includes erythroderma, diarrhea, and growth failure, may result from a variety of immunologic abnormalities, including Netherton's syndrome (Fig. 12-27, 12-28, 12-29, 12-30). A complete workup is mandatory in patients with this constellation of symptoms.