Bridget M. Bryer Groff, MD

A 4-year-old boy was referred for evaluation of refractory eczema that first appeared at 1 month of age. His mother thought that his skin always seemed “dirty” and she was unable to remove the scales completely. He was born via cesarean section because of failure of labor to progress; the delivery was otherwise uncomplicated. Development was normal. He had no history of asthma or allergies or family history of rashes.

On examination, the boy appeared healthy. He had fine, adherent, white to tan scales on his body, with relative sparing of the central face and axillae. No erythema or crusting was present. Hair and nails were normal. No eye abnormalities were noted. Testes were descended bilaterally. The clinical history and physical findings suggested a diagnosis of X-linked ichthyosis.

This X-linked recessive disease is characterized by a deficiency in the steroid sulfatase (STS) enzyme and affects 1 in 6000 male infants. The deficiency causes failure of keratinocytes to shed normally, resulting in hyperkeratosis and prominent, large, polygonal dirty brown scales on the neck, extremities, trunk, and buttocks. The condition generally appears as small, diffuse white scales that become larger and darker as the child ages. In contrast to atopic dermatitis, which typically begins at age 3 to 6 months, X-linked ichthyosis occurs at 2 to 6 weeks of age. It is constant, unlike the rash of atopic dermatitis, which often has flares and remissions. The scaling classically spares the flexural areas and face, which are often involved in children with atopic dermatitis.

 Ichthyosis vulgaris is also in the differential diagnosis of this condition and may be difficult to differentiate clinically. This condition is often described as thin, white to translucent scales that also spare the flexural areas. Ichthyosis vulgaris is not associated with the other findings discussed below. Ichthyoses are usually less pruritic than classic eczema. All of these conditions may improve with age.

 The diagnosis of X-linked ichthyosis may be suggested by biopsy and confirmed definitively with an enzyme assay that shows decreased STS activity.

X-linked ichthyosis is associated with comma-shaped corneal opacities in up to 50% of patients.

 These opacities do not affect visual acuity but may cause corneal erosions. Cryptorchidism occurs in 20% of infants and is associated with an increased risk of testicular cancer.

 These patients require a thorough genital examination and referral to a pediatric urologist if one or both testes are undescended. A deficiency of the STS enzyme in the placenta of a mother carrying an affected fetus can cause failure of labor to begin or progress. X-linked ichthyosis has also been associated with attention-deficit/hyperactivity disorder, because a deficiency in the STS gene affects the production of neurosteroids.

Treatment focuses on diminishing abnormal keratinization by facilitating the elimination of scales and preventing their proliferation. First-line therapy includes topical emollients and keratolytics, although the latter must be used with caution in young infants, because of potential for systemic toxicity. Other treatment options include petrolatum, 40% to 60% propylene glycol in water, alpha hydroxy acids, and lactic acid. Topical retinoids may also help.

 Oral retinoids are reserved for patients with severe disease.

In patients with a family history of the disease, prenatal diagnosis can be made via amniocentesis and chorionic villus sampling with an STS assay that detects the enzyme deficiency. Case reports have also described an association between STS deficiency and an undetectable unconjugated estriol in second-trimester maternal serum screening.

1. HernÃ¡ndez-Martin A, GonzÃ¡lez-Sarmiento R, De Unamuno P. X-linked ichthyosis: an update. 

2. Fernandes NF, Janniger CK, Schwartz RA. X-linked ichthyosis: an oculocutaneous genodermatosis. 

3. Brookes KJ, Hawi Z, Kirley A, et al. Association of the steroid sulfatase (STS) gene with attention deficit hyperactivity disorder. 

4. Watanabe T, Fujimori K, Kato K, et al. Prenatal diagnosis for placental steroid salfatase deficiency with fluorescence in situ hybridization: a case of X-linked ichthyosis. 

5. Langlois S, Armstrong L, Gall K, et al. Steroid sulfatase deficiency and contiguous gene deletion syndrome amongst pregnant patients with low serum unconjugated estriols. 

Articles

A 4-year-old boy was referred for evaluation of refractory eczema that first appeared at 1 month of age.

X-Linked Ichthyosis

An 18-year-old boy presented with a severalmonth history of an intermittent, very pruritic rash on his back that did not improve with topical corticosteroids. Physical examination revealed grouped erythematous papules with a few scattered small vesicles on his posterior neck and bilateral posterior shoulders at the location where his backpack frequently rubbed. A biopsy of the lesion with immunofluorescence studies showed subepidermal separation with collections of neutrophils at the dermal papillary tips and granular IgA deposits in the dermal papillae. On the basis of the biopsy results, dermatitis herpetiformis was diagnosed.

Dermatitis herpetiformis is an uncommon skin condition that usually presents in young adults but can develop at any time. It is a classic cutaneous manifestation of glutensensitive enteropathy, or celiac disease-also referred to as "celiac sprue." The rash is often intermittent, usually coinciding with dietary exposure to gluten.

The typical presentation involves grouped vesicles and papules concentrated on the extensor elbows, knees, and buttocks, often with overlying excoriations secondary to the marked pruritus. The rash tends to occur in areas of pressure; in this case, the diagnosis was difficult because the shoulders are not usually considered areas of pressure and it is unusual for dermatitis herpetiformis to present there. In children, dermatitis herpetiformis may have an atypical appearance and resemble atopic dermatitis, scabies, impetigo, or papular urticaria.

 This case illustrates the variable clinical presentations of dermatitis herpetiformis, especially in younger patients.

Only 20% of persons with dermatitis herpetiformis have GI complaints, although 90% have evidence of intestinal involvement on further evaluation.

Patients with celiac disease may also complain of arthritis, peripheral neuropathy, ataxia, anemia, and recurrent aphthous ulcers. In addition, they have an increased risk of other autoimmune disorders, including thyroid disease, autoimmune hepatitis, type 1 diabetes, and psoriasis.

 Perhaps the most serious sequela is the increased risk of intestinal and extraintestinal lymphomas.

The diagnosis of dermatitis herpetiformis can be established in several ways. Clinical suspicion is important, but a skin biopsy with direct immunofluorescence of uninvolved skin is the gold standard for confirmation of the diagnosis. A less invasive study-testing for IgA antiepidermal transglutaminase antibodies-detects serological evidence of dermatitis herpetiformis and is very sensitive. Testing for anti-tissue transglutaminase antibodies can reveal a correlation with the degree of intestinal involvement and can be used to document adherence to a gluten-free diet.

 However, intestinal involvement is confirmed by a small-bowel biopsy.

Treatment of the rash includes the use of potent topical corticosteroids, which are usually only partially effective. Oral dapsone is very effective and can relieve itching in a few days; however, it can also lead to relapse on discontinuation.

 Dapsone should not be used in patients with glucose-6-phosphate dehydrogenase deficiency because of the risk of hemolytic anemia. Although dapsone is very effective at clearing the rash, treatment should center on adherence to a gluten-free diet because the risk of subsequent lymphoma development is not decreased by dapsone therapy.

On further questioning, this patient did report frequent episodes of diarrhea. Both the rash and GI symptoms resolved over several months with adherence to a gluten-free diet.

 Caproni M, Antiga E., Melani L, Fabbri P; Italian Group for Cutaneous Immunopathology. Guidelines for the diagnosis and treatment of dermatitis herpetiformis. 

 Bolognia JL, Jorizzo JL, Rapini RP, eds. 

 Hernandez L, Green PH. Extraintestinal manifestations of celiac disease. 

 Rose C, Armbruster FP, Ruppert J, et al. Autoantibodies against epidermal transglutaminase are a sensitive diagnostic marker in patients with dermatitis herpetiformis on a normal or gluten-free diet. 

An 18-year-old boy presented with a several-month history of an intermittent, very pruritic rash on his back that did not improve with topical corticosteroids. Physical examination revealed grouped erythematous papules with a few scattered small vesicles on his posterior neck and bilateral posterior shoulders at the location where his backpack frequently rubbed.

Atypical Dermatitis Herpetiformis

A healthy term infant born via normal vaginal delivery was noted at birth to have numerous small vesicles involving most of his face and upper chest. He was transferred to the neonatal ICU for suspicion of disseminated herpes simplex. On examination, the infant had small, 1- to 2-mm, superficial, clear vesicles that were confluent on the forehead, eyelids, nose, cheeks, neck, and upper back. A Tzanck test was negative for multinucleated giant cells. Skin biopsy confirmed a diagnosis of miliaria crystallina.

Miliaria crystallina is a common disease of the eccrine sweat glands; it occurs in up to 5% of infants, most frequently around 1 week of life. Epidemiological studies do not show a race or sex predilection. Development of miliaria before the fourth day of life is unusual.

 The condition develops most often in warm or humid environments, including incubators, and after treatment with cholinergic or adrenergic medications.

 Additional risk factors include exposure to UV light, bacterial colonization of the skin with 

Miliaria has been classified into various types on the basis of the level of obstruction of the eccrine gland; miliaria crystallina represents the most superficial occlusion-occlusion that occurs in the subcorneal and intracorneal epidermis.

The lesions of miliaria crystallina are 1- to 2-mm noninflammatory clear vesicles on a clear base that easily rupture with minimal pressure. They appear on the forehead initially and may become generalized, with a predilection for areas covered by clothing and intertriginous areas.

 The clinical presentation is the result of eccrine duct obstruction leading to rupture, which causes sweat to become trapped in the skin. The cause of the obstruction is not understood, but bacteria may play a role in its pathogenesis.

 A scraping of a vesicle does not reveal inflammatory cells, and biopsy is not routinely indicated.

The lesions of miliaria crystallina are generally asymptomatic, self-limited, and without complications. The vesicles rupture and desquamate without treatment several days after they appear. To facilitate regression of the rash, move affected infants to a cooler, less humid environment. Bathing patients in cool water can also hasten resolution of the rash.

 Although the rash clears within several days, anhidrosis takes 2 weeks to resolve; this coincides with the time necessary for eccrine gland turnover.

Bacterial superinfection can occasionally complicate deeper variants of miliaria but is uncommon in miliaria crystallina.

 Miliaria crystallina is important to recognize because conditions with similar presentations are more serious; the latter include herpes simplex virus infection, staphylococcal scalded skin syndrome, congenital candidiasis, incontinentia pigmenti, and epidermolysis bullosa.

 Gan V, Hoang M. Generalized vesicular eruption in a newborn. 

 Wolff K, Goldsmith L, Katz S, Gilchrest B, eds. 

Fitzpatrick's Dermatology in General Medicine

. 7th ed. New York: McGraw-Hill Companies; 2008:730.

. Oxford, UK: Wiley-Blackwell; 2006:63-65.

A healthy term infant born via normal vaginal delivery was noted at birth to have numerous small vesicles involving most of his face and upper chest. He was transferred to the neonatal ICU for suspicion of disseminated herpes simplex. On examination, the infant had small, 1- to 2-mm, superficial, clear vesicles that were confluent on the forehead, eyelids, nose, cheeks, neck, and upper back. A Tzanck test was negative for multinucleated giant cells.

Extensive Miliaria Crystallina

A healthy 9-year-old girl presented with pruritic, darkly colored papules and linear lesions on the left side of her face. She had recently been on a hiking trip with her family. Examination revealed erythematous papules and linear streaks with an overlying black substance that resembled black lacquer paint. "Black-spot" poison ivy was diagnosed.

Poison ivy, or rhus dermatitis, is one of the most common causes of allergic contact dermatitis in the United States. Poison ivy belongs to the 

 genus of the Anacardiaceae family of plants, which also includes poison oak and poison sumac. The classic cutaneous reaction of multiple pruritic, erythematous papules and vesicles, often in a linear distribution, arises because of traumatic contact with urushiol, which is found in the plant's sap.

When urushiol is exposed to humid, warm conditions, it is oxidized by lactase and turns into a dark brown to black lacquer-like substance.

 High concentrations of the oxidized resin can result in black-spot poison ivy, which is both an allergic and irritant dermatitis. Black-spot poison ivy is thought to be an uncommon presentation of poison ivy because the concentrated sap is often diluted by perspiration; also, many people notice the colored resin and avoid contact with it.

Black-spot poison ivy is treated in the same manner as common poison ivy dermatitis. After suspected exposure to poison ivy, the affected area should be immediately irrigated. Topical corticosteroids may be helpful if used early in mild cases. Treatment of extensive poison ivy often requires systemic corticosteroids, which must be continued for 2 to 3 weeks to avoid the common "rebound" phenomenon of worsening dermatitis.

 Kurlan JG, Lucky AW. Black spot poison ivy: a report of 5 cases and a review of the literature. 

A healthy 9-year-old girl presented with pruritic, darkly colored papules and linear lesions on the left side of her face. She had recently been on a hiking trip with her family. Examination revealed erythematous papules and linear streaks with an overlying black substance that resembled black lacquer paint.

Author | Bridget M. Bryer Groff, MD

Articles

X-Linked Ichthyosis

Atypical Dermatitis Herpetiformis

Extensive Miliaria Crystallina

Black-Spot Poison Ivy