Cyclic Psoriasis

Mectianism of Action A cyclic polypeptide that inhibits both cellular and humoral immune responses by inhibiting interleukin-2, a proliferative factor needed for T-cell ac-tivityT herapeuticEffect Prevenfs organ rejecfion and relieves sympfoms of psoriasis and arfhrifis. 

Cyclic Nucleotides in Psoriasis - In 1971 Voorhees and Duell proposed the first working model of a potentially deranged cyclic AMP system in psoriasis. 13 The model was based on the fact that three characteristic features of the lesional epidermis of psoriasis are glycogen accumulation,8 decreased terminal differentiations and increased proliferation.14 In other tissues and experimental systems, cyclic AMP was capable of reversing... 

Our measurements indicate that the cyclic AMP/cyclic GMP ratio in psoriatic lesions is reduced.1 The level of cyclic GMP is consistently increasedl whereas depending on the study, the level of cyclic AMP is either slightly increased,19 normal 9 or modestly reduced.1 Perhaps the most important observation is that whereas most metabolic parameters in psoriasis are unequivocally elevated20,21 as the case with any acti-... 

In less well controlled studies topical theophylline, with or without topical dibutyryl cyclic AMP or a cyclic AMP analog, has shown modest efficacy in psoriasis.29,30 An uncontrolled clinical trial of oral theophylline is said to have demonstrated beneficial results in psoriasis.31 In two uncontrolled clinical studies of intramuscular dibutyryl cyclic AMP, studies inspired by our earlier biochemical studies on cyclic nucleotides in psoriasis,Chinese physicians in Shanghai considered the drug effective in 80% of 69 patients treated.32,33 in the Chinese studies, reported side effects were insignificant and thus it should be possible to duplicate their study but using a double blind design. In view of the excellent re-... 

Triamcinolone to be used topically is generally dispensed as its more potent and lipophilic acetonide, a 16a,17a-methylenedioxy cyclic ketal or isopropylidene derivative (Fig. 33.14) (see Inhaled and Intranasal Glucocorticoids). It is effective in the treatment of psoriasis and other corticoid-sensitive dermatologic conditions. Topically, triamcinolone acetonide is a more potent derivative of triamcinolone and is approximately eight times more active than prednisolone. The side effects of the drug, however, have occurred with sufficient frequency ... 

Colchicine with its microtubule-disrupting properties limits the chemotactic and phagocytic activity of polymorphonuclear lymphocytes. It also induces the release of prostaglandin E, a suppressor of leukocyte function by increasing the level of cyclic adenosine monophosphate [39]. Furthermore, the ability of colchicine in inhibition of IL-1 production and histamine release makes it an excellent drug for a number of dermatitis-related complexities like psoriasis, Behget s syndrome, recurrent aphthous stomatitis, leukocytoclastic vasculitis and urticarial vasculitis, bullous disease, scleroderma, fibromatosis. Sweet s syndrome, amyloidosis, and many more [40]. 

The role that cyclic nucleotides may play in the etiology and/or maintenance of a number of disease states is becoming clearer. In asthma, the ability of patients with this disease to excrete increased amounts of cyclic AMP in urine in response to epinephrine is greatly diminished, possibly due to a disease-related decrease in the sensitivity of adenylyl cyclase (AC) to the catecholamine. This lack of AC sensitivity however could be reversed by corticoid therapy in accord with the long established permissive effects of these hormones on cyclic AMP synthesis. In nephrogenic diabetes insipidus, diminished urinary production of cyclic AMP in response to ADH was also reported. Other conditions that may involve deficient cyclic AMP production include hypertension , psoriasis and stroke . On the other hand, cyclic AMP production appears... 

Cyclic GMP, which appears to share with cyclic AMP the secondary messenger function in many systems, also appears to be elevated in psoriasis... 

Cyclic and dibutyryl-cyclic adenosine 3, 5 -monophosphate (cAMP and DB cAMP) were both utilized in the treatment of psoriasis by a Shanghai study group (39 ). 20 patients received cAMP while 49 received DB cAMP. The dosage was up to 80 mg Lm. daily for 20—90 days. Side effects were recorded in 8 patients on cAMP and 47 on DB cAMP. They included malaise, dizziness, chills, drowsiness, nausea, anorexia, blurred vision, abdominal pain, flushing, urticaria, Koebner s phenomenon and local indurar tion. No interruption of treatment was necessary. 

---