Papaverine and Ro 20-1724 inhibit cyclic nucleotide phosphodiesterase activity and increase cyclic AMP levels in psoriatic epidermis in vitro.

The comparative inhibitory potency of papaverine and Ro 20-1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone) on cyclic AMP-phosphodiesterase (cAMP-PDE) and cyclic GMP-phosphodiesterase (cGMP-PDE) activities and their effect on the levels of cAMP and cGMP were examined in psoriatic epidermis. At concentrations of 5 X 10(-4) M, papaverine inhibited the hydrolysis of both cAMP and cGMP by either the low or high Km psoriatic epidermal PDE nearly 100% (p less than .0001) while Ro 20-1724 selectively inhibited the hydrolysis of cAMP 94% (p less than .0001) but had no significant effect on cGMP hydrolysis. When keratomed psoriatic epidermal slices were incubated in 5 X 10(-4) M papaverine or Ro 20-1724 the tissue levels of cAMP were increased 343% or 1395% respectively (p less than .001) with no concomitant change in the levels of cGMP. Selective inhibition of cAMP hydrolysis by Ro 20-1724 and its greater effectiveness in elevating cAMP levels in slices of psoriatic epidermis is one explanation for its clinical superiority in treating psoriatic lesions.

Ro 20-1724: an agent that significantly improves psoriatic lesions in double-blind clinical trials.

Two double-blind studies comparing the effectiveness of the cyclic nucleotide-altering agent (4-[3-butoxy-4-methoxybenzyl]-2-imidazolidinone) (Ro 20-1724) vs vehicle have demonstrated that this compound can improve psoriatic lesions. Although Ro 20-1724 was not as effective as intensive occlusive treatment of psoriatic lesions with 0.025% triamcinolone acetonide, Ro 20-1724 had no adverse systemic or cutaneous effects. Ro 20-1724 and other cyclic nucleotide-altering agents may have therapeutic potential in the future treatment of psoriasis.

Arteriovenous fistula. Cutaneous manifestations.

The association between congenital large-vessel arteriovenous (AV) fistulae of the extremities with Kaposiform acroangiomatosis is well established. Based on pathogenetic considerations, it is likely that many benign, cutaneous angiomatoses represent minute or microscopic AV fistulae. Combined large vessel and small vessel congenital AV fistulae of the extremity would result in the previously mentioned syndrome.

Disseminated granuloma faciale.

Granuloma faciale is a well-defined entity that almost exclusively involves the face, although it has been reported in extrafacial locations. The infrequent reports of extrafacial lesions may reflect the inconspicuous nature of extrafacial lesions or a failure to specifically examine the patient for such lesions.

Circumscribed scleroderma with immunologic evidence of systemic lupus erythematosus.

An 8-year-old girl initially manifested clinical and histopathologic findings of circumscribed scleroderma. She had both linear and plaque lesions. Although she was free of constitutional symptoms, laboratory evaluation revealed substantial evidence of systemic lupus erythematosus (SLE). This included a positive anti-nuclear antibody test (rim pattern), positive LE cell preparation test, elevated anti-double-stranded DNA activity, positive lupus band test (IgM and C3) in involved and uninvolved skin, and renal biopsy findings consistent with SLE. Sclerodermatous change as an initial sign of SLE is rare. We review previous reports of an association of circumscribed scleroderma, especially the linear form, with serologic evidence of systemic autoimmune disease.