Anetoderma: Biochemical and ultrastructural demonstration of an elastin defect in the skin of three patients

Three patients with localized cutaneous lesions characteristic of anetoderma were studied. Clinically, the onset of the disease was between the ages of 17 and 25, and numerous flaccid, saclike skin lesions developed over several subsequent years. Histologically, the lesions were characterized by paucity and fragmentation of the elastic fibers. Electron microscopy demonstrated that the elastic fibers, both in papillary and deep reticular dermis in the lesional skin, were fragmented and irregular in appearance. The concentration of elastin, determined by a radioimmunoassay of desmosine, an elastin-specific cross-link compound, was markedly reduced in the lesions, as compared with unaffected skin from the same patients or with normal skin from unrelated control subjects. In contrast, the concentrations of hydroxy pro line, an index of collagen, or deoxyribonucleic acid (DNA), a measure of cellularity, were not changed in the lesions. Thus, the results indicate that in the three patients studied, the elastic fibers are defective and reduced in quantity. These observations suggest that the deficiency of elastin in the dermis may lead to development of the cutaneous lesions of anetoderma.     

Psoriasis improved by anthracene with near ultraviolet light

Anthracene with near ultraviolet (UV) light (UVA, 320--400 nm) has been shown previously to inhibit epidermal deoxyribonucleic acid (DNA) synthesis and mitosis. This suggested that the combination of anthracene and UVA light could suppress the rapidly proliferating epidermis of psoriasis. In this preliminary clinical study, anthracene plus UVA light improved psoriasis as shown by thinning of plaques and decreased scale in four of five patients, with complete or almost complete clearing in two of these four patients. These findings indicate that anthracene with UVA light might be helpful in the control of psoriasis.     

Pathogenesis of papular urticaria

The presence of immunoglobulin and complement deposits in the skin of three patients with papular urticaria suggests that these lesions may be due to a cutaneous vasculitis. These deposits were most frequently found in biopsy specimens taken from lesions within 24 hours of their development. The presence of granular deposits of Clq, C3, and IgM in the walls of the superficial dermal blood vessels suggests that immune complexes (IgM aggregates) may be primarily involved in the pathogenesis of these lesions, with complement activation initiated by Clq through the classical pathway.     

Suppression of histamine-induced pruritus by hydroxyzine and various neuroleptics.

This study evaluates the ability of hydroxyzine and various neuroleptics to suppress histamine-induced pruritus in ten volunteer subjects with the use of a double-blind crossover protocol. The itch threshold was determined in each volunteer by intradermal injection of gradually increasing concentrations of histamine. Volunteers were then given the study drugs and placebo at the same interval of time, under near identical conditions, and the itch threshold was determined. Thiothixene, hydroxyzine hydrochloride, chlorpromazine, thioridazine, and a lactose placebo were evaluated. Compared to other drugs, hydroxyzine alone was more effective in the suppression of histamine-induced itch. Consequently, hydrozyzine may be more effective in histamine-induced pruritus. The neuroleptic drugs used in this study do not significantly suppress histamine-induced pruritus, but they may be beneficial in nonhistamine-induced pruritus or psychogenic pruritus.     

Cell surface carbohydrates in psoriasis: Defective cytoplasmic transport by glycoconjugates carrying fucose residues suggested by lectin staining

Eleven biopsy specimens of normal skin and twenty-four biopsy specimens of psoriatic lesions were examined histochemically by using several lectins (Ulex europaeus, UEA-1; Dolichos biflorus, DBA; Bandeirea simplicifolia, BS-I; Concanvalia ensiformis, Con A; Triticum vulgaris, WGA; Ricinus communis, RCA; Arachis hypogoea, PNA) in order to evaluate the presence and distribution of various carbohydrates in normal and psoriatic keratinocytes. The findings revealed that keratinocytes from psoriatic lesions are distinguished by a different composition of carbohydrate residues incorporated in their plasma membranes. In particular, the intracellular transport of alpha-L-fucose, alpha-D-mannose, and alpha-D-glucose to the plasma cell membrane is impeded, whereas their synthesis in the cytoplasm of the psoriatic keratinocytes is largely unaltered. In addition, due to the lack of terminal alpha-L-fucose, the alpha-D-N-acetyl-galactosamine and alpha-D-galactose residues cannot be transferred to the plasma membranes and, therefore, the antigens for blood groups A and B remain incomplete in psoriatic epidermis. On the basis of these findings and in comparison with previous findings of our group on hyperproliferative, malignant keratinocytes, it is concluded that particularly the disordered cytoplasmic transport of alpha-L-fucose-carrying glycoconjugates may represent a specific defect in psoriasis, possibly linked with the pathogenesis of this disease.     

Hepatoerythropoietic porphyria: A variant of childhood-onset porphyria cutanea tarda: Porphyrin profiles and enzymatic studies of two cases in a family

Hepatoerythropoietic porphyria is a rare variant of porphyria cutanea tarda, manifested clinically as photosensitivity starting in early childhood. Biochemically, there are elevated levels of protoporphyrin in erythrocytes and acetate-substituted porphyrins in the plasma, urine, and feces. Uroporphyrinogen decarboxylase activities in these patients are markedly suppressed. Thus far, only nine patients have been reported. We hereby describe the clinical manifestations, histologic changes, porphyrin profiles, and erythrocyte uroporphyrinogen decarboxylase determinations of two additional patients, 9-year-old and 7-year-old siblings, that are consistent with those of nine previously reported patients with hepatoerythropoietic porphyria.     

Punctate hyperkeratosis of the palms and soles. An ultrastructural study

Punctate hyperkeratosis of the palms and soles is an uncommon autosomal dominant condition. We report a 65-year-old man with this condition and review the literature. With electron microscopy, we have examined both clinically affected and adjacent clinically unaffected palmar skin. The only ultrastructural differences noted were a thicker keratin layer and hypertrophic nucleoli in the basal cell layer and stratum spinosum in the clinically affected skin. This nucleolar hypertrophy suggests that there may be increased metabolic activity in the clinically affected skin which is contributing to the abnormal keratinization.     

Psoralen-containing sunscreen is tumorigenic in hairless mice

Sunscreens containing 5-methoxypsoralen (5-MOP) are currently being marketed to promote tanning by inducing psoralen-mediated ultraviolet (UV) A (320-400 nm) melanogenesis. The rationale is that this may prevent UVB (290-320 nm) radiation-induced skin damage. However, mouse studies have shown that 5-MOP has the same cutaneous photocarcinogenic potential as 8-methoxypsoralen. In addition, the 5-MOP--containing sunscreen Sun System III (SS III), when combined with UVA, induces epidermal ornithine decarboxylase activity, an enzyme associated with tumor promotion. Therefore, we investigated whether SS III had sufficient psoralen concentration to be tumorigenic in hairless mice exposed to chronic, intermittent UVA radiation. SS III was applied to hairless mice 5 days per week for 20 weeks. After each application the mice were exposed to 2.5 to 10 joules/cm2 UVA radiation. All test groups developed atypical squamous papillomas in direct proportion to the dosage of UVA radiation received. A shorter latency period for tumor development was seen with larger UVA doses. Test animals followed up to 1 year developed invasive squamous cell tumors. Control groups (SS III without UVA and UVA without SS III) remained free of tumors. Animals receiving SS III plus UVA developed persistent skin thickening and increased dermal cyst formation similar to that reported with chronic exposure to UVB, a known carcinogenic wavelength. Over-the-counter sunscreens containing 5-MOP do contain sufficient psoralen concentrations to cause cutaneous phototoxicity and photocarcinogenicity in mice, and their use in humans should be discouraged in the interest of preventing further UV-induced skin damage and skin cancer.     

PUVA treatment of erythrodermic and plaque type mycosis fungoides

Five patients with plaque type mycosis fungoides (MF) and five patients with erythrodermic MF responded favorably to oral psoralen photochemotherapy (PUVA). The mean total UVA irradiation dose was less for erythrodermic than for plaque type MF, but the mean number of treatments to achieve clearing was greater in the erythrodermic patients. Histologic examination at clearing revealed persistence of an inflammatory infiltrate in the lower dermis in most cases. Subsequent recurrent lesions in five patients revealed a more extensive dermal inflammatory infiltrate, although findings were not always diagnostic of MF due to a lack of epidermal involvement. Resumption of more intensive PUVA therapy again resulted in clinical clearing in all five patients. The follow-up period for six patients who received long-term PUVA maintenance ranged from 1 1/2 to 3 1/2 years. During PUVA therapy, five of ten patients developed epithelial malignancies or premalignancies, and one patient developed a malignant fibrous histiocytoma. Most of these patients had received prior treatment with electron beam and topical nitrogen mustard.     

Isotretinoin treatment of acne and related disorders: an update

In the one year since isotretinoin has been available in the United States for the treatment of severe, recalcitrant, nodulocystic acne, there has been extensive clinical verification of the reports of its dramatic efficacy in the treatment of this troublesome disease. Proper selection of patients, as well as treatment with adequate doses of drug for 3 to 5 months, will most often result in significant clinical improvement or total clearing. Although dosages of less than 1 mg/kg/day may produce a nearly equivalent degree of improvement with somewhat fewer or less severe side effects, the recommended daily dose remains 1 mg/kg/day because lower dosages are associated with more frequent relapses. In severe cases, the daily dosage may be increased to 2 mg/kg/day. Teratogenicity, elevation of serum triglycerides, liver function abnormalities, pancreatitis, and pseudotumor cerebri may all be associated with isotretinoin therapy and require close monitoring of the patient.     

Neonatal lupus erythematosus, multiple thromboses, and monoarthritis in a family with Ro antibody

We describe a family afflicted with striking clinical and serologic autoimmune features. The mother and maternal uncle of a patient with neonatal lupus had rheumatic disease manifestations. All three had Ro antibodies (SS-A) in their sera, as well as La antibody (SS-B). The 17-year-old mother developed postpartum inflammatory monoarthritis of the right knee and had a positive lupus band test. The uncle at the age of 26 developed a fulminant disease most consistent with systemic lupus erythematosus (SLE); initial manifestations were myocardial infarction, deep vein thrombosis, and the nephrotic syndrome. Although it is known that mothers of neonatal lupus infants can develop SLE postpartum, the development of severe disease in the maternal uncle suggests the relevance of identifying seropositive relatives of individuals with neonatal lupus.