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The contribution of psychosomatic factors toward the morbidity associated with psoriasis should be evaluated in the context of the patient's developmental stage and life situation. The skin, as a sensory organ, plays a critical role in an individual's physical and emotional growth in early life. The skin also plays an integral role as an organ of communication throughout life and greatly affects an individual's body image and self-esteem. If these factors are not taken into consideration, the morbidity associated with psoriasis may increase, or the patient may remain dissatisfied with treatment even in the face of clinically satisfactory treatment outcome. Some recent studies indicate that the adverse impace of psoriasis upon the quality of life can result in significant chronic stress, which may in turn exacerbate the psoriasis in a subgroup of patients. As disease-related stress is present in every patient to some degree, the dermatologist should regularly assess the psychosocial impact of the disease. Certain personality factors, such as a tendency to want the approval of others and difficulty with assertion of angry feelings, may make the patient with psoriasis more vulnerable to stress and contribute toward the stress reactivity of the disease. The presence of depression in psoriasis may modulate itch perception, exacerbate pruritus, and lead to difficulties with initiating and maintaining sleep. Helping the patient to develop assertiveness skills in addition to supportive psychotherapy may facilitate the patient's capacity to cope with the daily stresses associated with psoriasis. Treatment of depressive symptoms may prove to be a helpful adjunct in the management of pruritus and sleep difficulties in psoriasis.

Tretinoin has previously been used for the treatment of acne. Recent studies, however, demonstrating the efficacy of topical tretinoin in the treatment of photodamaged skin have led to its widespread use for this entirely new indication. When prescribing tretinoin for photodamaged skin rather than acne, physicians must take into consideration a new set of issues. Patients must be selected based on their commitment to a total sun-avoidance regimen. Evaluation of photodamage must be careful and thorough prior to initiating topical tretinoin therapy. Global assessment of a patient's photodamaged skin should be made before therapy and at all follow-up visits. The patient population treated for photodamage tends to be older than that using topical tretinoin for acne; therefore, the treatment regimen must account for the different clinical and physiological characteristics of older patients' skin.

In a double-blind, vehicle-controlled study, all of six psoriatic plaques treated with intralesional cyclosporine administered three times weekly for 4 weeks showed complete clearing or incomplete but significant clearing in comparison with vehicle-treated plaques (p less than 0.01). Epidermal thickness decreased from 0.42 +/- 0.07 to 0.27 +/- 0.08 mm at 4 weeks (p less than 0.03). Biopsy specimens obtained on day 5, before any clinical improvement, revealed a significant reduction of epidermal DR+CD1- antigen-presenting cells, epidermal and dermal monocytes, and keratinocyte intercellular adhesion molecule-1 expression. By day 5 the stratum corneum reverted to normal in the plaques receiving cyclosporine. Pain at the injection site was the major side effect. Steady-state blood cyclosporine levels ranged from 20 to 30 ng/ml during the first 12 hours after injection and became undetectable at 48 hours. These data suggest that cyclosporine improves the skin of patients with psoriasis by a local mechanism of action.

Two patients with severe chronic lichen planus were successfully treated with oral cyclosporine (6 mg/kg/day). A response was noted within 4 weeks, and complete clearing was achieved after 8 weeks of treatment. No significant adverse effect was noted. The patients have remained in remission 3 and 10 months after therapy, respectively. Clinical improvement was accompanied by significant reduction in the T cell infiltrate in the skin. Abnormal expression of keratinocyte intercellular adhesion molecule-1 (ICAM-1), which was present before therapy, became undetectable after 1 week of cyclosporine therapy, before any significant clinical and histologic change.

In a double-blind trial, 21 patients with severe plaque psoriasis were randomly assigned to receive oral cyclosporine, 14 mg/kg/d, or its vehicle. After four weeks of therapy the 11 cyclosporine recipients had the following response to treatment: two had total clearing and six improved markedly, two moderately, and one minimally; whereas ten vehicle-treated patients showed no change or minimal improvement. Vehicle-treated patients, after a switch to cyclosporine for four weeks, demonstrated impressive improvement similar to that seen in patients who initially received only cyclosporine. Moderate or marked improvement or total clearing was noted in 17 (81%) of 21 and 20 (95%) of 21 after one and four weeks of therapy, respectively. Mitotic figures and leukotriene B4 levels in lesions decreased 86% and 64%, respectively, after seven days of cyclosporine therapy. Mononuclear (including activated T cells) and polymorphonuclear leukocyte infiltrates were markedly reduced in lesions of all patients after seven days of cyclosporine therapy. These results suggest that psoriasis may have an immunologic basis mediated by activated T cells and/or other immune cells; if a long-term regimen with a favorable efficacy-side effect ratio can be determined, cyclosporine would be a significant advance in the treatment of psoriasis.

In an open trial, five patients with lamellar ichthyosis showed no response to four weeks of treatment with oral cyclosporine (cyclosporine A) (6 mg/kg/d). Histologic examination of lamellar ichthyosis revealed hyperkeratosis; psoriasiform acanthosis; dilated, tortuous capillaries; and a slight perivascular lymphocytic infiltrate. Immunofluorescence studies revealed, in the epidermis, normal numbers of T6+DR+ Langerhans' cells and an absence of T cells and intercellular adhesion molecule-1 expression. In the papillary dermis, there were prominent capillaries as detected by staining with anti-factor VIII-related antigen. The endothelial cells also expressed large amounts of HLA-DR and intercellular adhesion molecule-1, suggesting that they were activated. Only occasional Langerhans' cells were found in the dermis. Histologic and immunofluorescence findings were unchanged with cyclosporine therapy. The effects of cyclosporine on lamellar ichthyosis are contrasted with those reported for psoriasis. Since lamellar ichthyosis and psoriasis share similar features of epidermal hyperproliferation and the presence of activated, dilated, tortuous vessels, but differ in the lack of immunologic cellular activity, their contrasting response to cyclosporine suggests that the target of the action of cyclosporine is the immune system rather than the keratinocyte or the endothelium. However, other factors may have to be considered.

We investigated changes in serum triglyceride, cholesterol, and high-density lipoprotein cholesterol (HDLC) levels during etretinate administration in 21 patients with psoriasis. Mean serum triglyceride and cholesterol values showed a statistically significant increase during etretinate therapy compared with placebo treatment; mean HDLC levels did not change. During etretinate therapy, elevations out of the normal range occurred in 77% of the patients for serum triglycerides and 25% for serum cholesterol. Eight weeks after discontinuation of the drug regimen, patients' mean serum triglyceride and cholesterol levels were not statistically different from those found prior to therapy. Nevertheless, eight weeks after therapy had been stopped, six (32%) of 19 patients had cholesterol values that were still 20% or more above their baseline levels; the prolonged etretinate excretion time could have been responsible. The mechanisms for the etretinate-induced lipid elevations are unknown.

5-Bromodeoxyuridine (BUDR), a halopyrimidine thymidine analogue, is incorporated into the DNA of dividing cells and causes photoradiosensitization. Twenty-five patients with malignant astrocytomas were treated with continuous intracarotid BUDR radiosensitization and radiotherapy for 8 1/2 weeks. Unique dose-limiting mucocutaneous complications were encountered. Ipsilateral facial dermatitis with epilation of eyebrows and eyelashes, ocular irritation, and bilateral nail dystrophy developed in all patients. Less common reactions included oral ulceration in six patients, body exanthem on the trunk in five, and atypical erythema multiforme major in one.

Keratomed epidermal tissue from normal individuals and from the lesional and non-lesional skin of psoriasis patients served as source materials for the extraction, separation, and quantitation of eicosanoids that may be important to cutaneous function and pathophysiology. The eicosanoids were extracted in ethanol and buffer, partially purified on SEP-PAKs, separated by reverse phase microbore high-performance liquid chromatography, and quantitated by radioimmunoassay or integration of absorbency peaks obtained by high performance liquid chromatography. The involved areas from psoriasis patients contained a statistically significant seven- to 11-fold increase in the levels of leukotriene B4, 13-hydroxyoctadecadienoic acid-like compound, 15-hydroxyeicosatetraenoic acid compound and 12-hydroxyeicosatetraenoic acid in comparison to normal samples and a three- to sevenfold increase in comparison to uninvolved tissue. The uninvolved areas contained 40% to 100% increases in the levels of these compounds in comparison to normal tissue; these increases were statistically significant except for 13-hydroxyoctadecadienoic acid-like compound. From a single keratome biopsy, multiple eicosanoids can be separated and quantitated; in addition, levels before, during, and after therapy for psoriasis may be compared.

Among 82 inpatients with psoriasis, 67% (55 patients) reported moderate or severe pruritus. The degree of depressive psychopathology discriminated between the mild, moderate, and severe pruritus groups at admission. Prospectively, the change in depression scores correlated with the change in pruritus pretreatment to posttreatment. Pruritus severity did not correlate significantly with stress due to life events, age at onset, ethyl duration of psoriasis, age, sex, marital status, and average reported daily alcohol (ethanol) consumption. Among the objective dermatologic measures, including extent and severity of lesions, only the degree of perilesional irritation discriminated between the mild, moderate, and severe pruritus groups at admission, and prospectively, change in this measure correlated with the change in pruritus pretreatment to posttreatment. This finding was most likely related to the self-excoriation associated with pruritus. Intrapsychic factors (eg, the severity of depression) rather than external psychosocial or well-defined dermatologic factors, were the most significant correlates of pruritus in psoriasis.

We report on three cases of a novel syndrome associated with treatment for psoriasis with the retinoid etretinate. The distinctive features of this syndrome include rigidity that is restricted to the axial muscles, impairment of neck extension greater than flexion, impairment of anteflexion at the waist, severe impairment of lateral flexion at both the waist and the neck, and, in one case, rigidity of proximal lower extremity muscles. Peripheral nerve block extinguished the lower extremity rigidity in one patient, and two patients had a favorable response to Sinemet. One patient had persistence of symptoms and findings 2 years after discontinuation of etretinate. The clinical features of this syndrome are consistent with an effect of etretinate on central, possible catecholaminergic neurons.

Vitamin A and its synthetic congeners are known to produce a variety of skeletal abnormalities in patients on prolonged treatment with these medications. Two patients are described who developed posterior longitudinal ligament ossification following treatment with the synthetic retinoid 13-cis-retinoic acid. In both cases, this finding became apparent after other retinoid-induced skeletal abnormalities were observed and was less marked than the ossification of the anterior longitudinal ligament. Although spinal cord compression did not occur in our patients, patients on long-term retinoid therapy should be carefully observed for this complication.

The relation of renin-angiotensin status to general hemodynamics and to neurogenic vascular resistance was studied in patients with border-line hypertension. Plasma renin activity during standing was referred to a standard renin-urinary sodium nomogram derived from 18 normal subjects. Among 22 patients with borderline hypertension the renin level was high in 8, low in 4 and within normal limits in the remaining 10. In patients with borderline hypertension and high or normal levels of plasma renin activity, the blood pressure elevation was due to increased total peripheral vascular resistance. In contrast, in patients with low renin borderline hypertension, total peripheral resistance was not significantly elevated; the blood pressure elevation reflected a cardiac index 12 percent higher than that in normal subjects. The neurogenic contribution to total peripheral vascular resistance was assessed by studying the effects of alpha adrenergic blockade with phentolamine, after prior autonomic blockade of the heart with atropine (0.04 mg/kg body weight) and propranolol (0.2 mg/kg). Phentolamine (15 mg) produced an immediate reduction in total peripheral resistance of 12.0 +/- 6.7 percent in patients with high renin borderline hypertension (P less than 0.01) but no change in normal subjects or those with borderline hypertension and normal or low renin levels. Normalization of the blood pressure followed "total" autonomic blockade with atropine, propranolol or phentolamine only in patients with high renin borderline hypertension. It is concluded from these preliminary data that in high renin borderline hypertension the blood pressure elevation is sustained by neurogenic mechanisms. The elevated renin level in these patients is probably an expression of increased sympathetic nervous activity. Although the elevated plasma renin level may possibly be contributing to the generation of higher sympathetic tone, or data do not support a direct role of circulating angiotensin in the maintenance of the elevated vascular resistance.

A prospective evaluation of the efficacy and safety of oral ibuprofen and tetracycline hydrochloride was conducted for 8 weeks in patients with moderately severe acne. Sixty-eight patients were randomly assigned in a double-blind fashion to one of four regimens: (1) one 600 mg ibuprofen tablet plus one 250 mg tetracycline capsule four times daily; (2) one 600 mg ibuprofen tablet plus one placebo capsule four times daily; (3) one 250 mg tetracycline capsule plus one placebo tablet four times daily; and (4) one placebo tablet and one placebo capsule four times daily. Sixty patients completed the 8-week study. The mean percent improvement in the groups treated with ibuprofen and tetracycline (56% +/- 5 SE), ibuprofen alone (26% +/- 13 SE), or tetracycline alone (26% +/- 9 SE) was statistically significant. However, only the combination of ibuprofen and tetracycline therapy had an effect statistically better than the placebo response (16+ +/- 11 SE). Adverse effects were transient and were similar in all four groups.

Urticaria is one of the more common skin conditions seen by physicians. Physical agents are an important cause of urticaria, with pressure or shearing forces being the most common. Dermographism is due to a combination of pressure and shearing forces and is present in a large number of healthy individuals. The purpose of this article is to provide a review of dermographism and its clinical variants.

Using a Boyden chamber technic, we measured the directed chemotaxis of polymorphonuclear leukocytes obtained from control subjects or psoriasis patients when the leukocytes were placed in sera obtained from control subjects or psoriasis patients. The samples from patients were obtained before therapy and after 2 and 4 weeks of etretinate administration. Compared with control sera, the sera from seven untreated psoriasis patients significantly enhanced the chemotaxis of polymorphonuclear leukocytes from control subjects toward a chemotaxin (p less than 0.05). After 4 weeks of etretinate therapy, the chemotaxis-stimulating ability of the sera from psoriasis patients was no longer significantly greater than that of the control sera. This decline in the chemotaxis-stimulating activity of our patients' sera preceded significant clearing of their psoriasis. The levels of circulating etretinate in the blood of our patients could not account for the reduction. Etretinate therapy had no apparent direct effect on the chemotactic activity of polymorphonuclear leukocytes from the psoriasis patients but may act in part by reducing the inflammatory effects of psoriatic sera.

A patient with chronic cutaneous and pulmonary sarcoidosis, unresponsive to oral corticosteroid therapy, was treated with isotretinoin. The patient's cutaneous manifestations of sarcoidosis showed consistent improvement during the course of retinoid therapy. The lesions that responded earliest either resolved or showed the greatest reduction in size. The patient's WBC count increased and her angiotensin-converting enzyme level decreased during the first two months of isotretinoin therapy; both returned to pretreatment levels during the third month of therapy. Pulmonary function tests were unchanged after four months of treatment. Isotretinoin may be a useful therapeutic agent for cutaneous sarcoidosis. However, the possibility of spontaneous remission of the disease during the course of therapy cannot be excluded.

Results of a double-blind, randomized, placebo-controlled, parallel study in 37 patients indicate that terfenadine, 60 mg bid, is significantly more effective than placebo and as effective as hydroxyzine, 25 mg qid, in the treatment of chronic idiopathic urticaria without causing the somnolence that was associated with the use of hydroxyzine.

Cyclosporine, a potent immunosuppressive agent, has been successfully used in the treatment of several dermatologic conditions including psoriasis. However, the drug does have an array of toxic side effects that need to be carefully considered when determining the risk-benefit ratio for the treatment of skin disease. We present another potential adverse effect of cyclosporine, namely, a benign lymphocytic infiltrate. This eruption developed in a patient with psoriasis after only ten days of cyclosporine therapy. The exact mechanism by which cyclosporine induced the lymphocytic infiltrate is unknown, but it is postulated that cyclosporine caused an imbalance of T-cell regulatory systems, thus resulting in an expanded T-cell subpopulation and the clinical manifestation of erythematous papules and nodules.

We present an unusual case of nodular late syphilis in a 52-year-old black man who had grouped, violaceous, pruritic papulonodules. Overlapping features of both secondary and teritary stages of the disease were present. The clinical presentation and histopathology are discussed.

Since lipemia is commonly induced by retinoid therapy, we investigated the effects of etretinate administration on glucose metabolism by obtaining five-hour oral glucose tolerance tests in 23 patients before and after 20 weeks of etretinate therapy for psoriasis. Compared with pretreatment values, peak and aggregate levels for serum glucose and aggregate levels for serum insulin were significantly lower during therapy. The changes were not associated with obesity, weight loss during treatment, or pretherapy glucose tolerance or insulin secretion level. Of 11 patients with impaired or diabetic glucose tolerance prior to therapy, eight patients had improved glucose tolerance after 20 weeks of etretinate treatment. Despite inducing hypertriglyceridemia in most patients, etretinate therapy is associated with a reduction in glucose levels in response to a glucose load.

Acitretin, the principal and free acid metabolite of etretinate, was used to treat patients with stable, plaque-type psoriasis. For the first 8 weeks, 38 patients received placebo or acitretin, 10, 25, 50, or 75 mg daily, in a double-blind manner. After the double-blind phase, the patients were allowed to continue for a total of 6 months of acitretin therapy at an average dosage of 50 mg/day. When the patients flared after stopping therapy, an additional 6-month course of acitretin therapy was offered. Acitretin, which was as effective as etretinate, had to be given at a dosage of 50 mg/day or more to obtain a significant benefit. Side effects frequently occurred in patients receiving acitretin, 25 mg/day or more, but were generally mild and did not warrant discontinuation of therapy. They were similar to those of etretinate therapy; cheilitis, peeling of palms and soles, and alopecia occurred most frequently. The most common abnormal laboratory test results were elevations in serum triglycerides and, to a lesser extent, serum cholesterol and liver transaminase levels. Acitretin, in view of its much shorter half-life and similar efficacy and side-effect profile compared with etretinate, may be a preferable therapy for psoriasis, especially in women of childbearing age.

Epidermolysis bullosa is a rare hereditary mechanobullous skin disorder. Four patients with esophageal involvement are reported. These cases and review of reported cases of epidermolysis bullosa dystrophica-recessive (EBD-R) showed distinct clinical and roentgenographie features of esophageal involvement: diffuse inflammatory changes, motility disorders, small blisters or bullae seen as constant nodular-filling defects, esophageal ulcers, scars, pseudodiverticula, transverse and circumferential webs, various size strictures, shortening of the esophagus with development of traction hiatal hernia and gastroesophageal reflux, perforation, and complete obstruction of the esophageal lumen. Dysphagia is reversible when caused by bullae or webs and permanent when due to cicatrizing strictures. The strictures may remain unchanged in size for many years despite variations in dysphagic symptoms.

Twenty-six patients with a history of hospitalization for severe psoriasis were evaluated with regard to their use of inpatient therapy before and during therapy with etretinate. The duration of the pretherapy period and the etretinate treatment period averaged 5 and 4 years, respectively. Use of etretinate nearly eliminated inpatient therapy among these patients. Twelve of the patients stopped etretinate; their use of hospitalization for psoriasis remained below pre-etretinate levels in the two years after etretinate therapy was stopped. Etretinate therapy represents an effective and economical alternative to hospitalization for psoriasis treatment.

Cyclosporin A is a potent immunosuppressive drug with almost a decade of clinical use. Due to its lack of bone marrow toxicity, it has assumed a leading role in organ transplant surgery. Likewise, it has shown remarkable efficacy in psoriasis and has shown potential usefulness in other dermatologic diseases, most of which are thought to have an autoimmune T-cell-mediated pathogenesis. There are many other inflammatory skin conditions in which T lymphocytes represent a majority of the cellular infiltrates, and theoretically such disorders may be responsive to CsA. Diseases such as lichen planus, allergic contact dermatitis, photoallergy, and vitiligo are potential areas of further study. The potential use of topical and intralesional CsA also warrants further clinical evaluation. There are reports of topical CsA showing effectiveness for alopecia areata and nickel contact sensitivity. Griffiths et al. treated six psoriatic patients with 2% CsA ointment twice daily for 4 weeks. The response to placebo or CsA at the end of the study was similar in all patients. Notably, there was no measured systemic absorption and no change in blood pressure or renal function. We had similar unimpressive results in several patients treated with a 10% solution of CsA; minimal to no response was seen. Of great benefit would be an effective topical preparation without systemic absorption or toxicity. Future studies will need to carefully evaluate the vehicle used and the strength of topical CsA employed. The role of CsA in dermatologic disease still needs much investigation, both at the clinical and basic science levels. The studies to date show dramatic and exciting results. Indeed, CsA may well represent a major advance in the understanding and treatment of psoriasis. However, the decision to use CsA for nonfatal diseases such as psoriasis will require a careful balance between efficacy and toxicity. If long-term side effects can be avoided or kept within reasonably safe, acceptable limits, CsA holds great promise for the treatment of psoriasis. It may at times be used as an acute intervention, with a relatively large, initial dose for a short period of time to quickly clear severe psoriasis. This could be followed by either a reduction to a lower and safer maintenance dose or a program of other treatments. Cyclosporin A may also prove useful alone in very low doses or in combination therapy, as with UVB or PUVA. Optimal dosing protocols are currently under investigation.

We evaluated the effects of long- and short-term isotretinoin therapy on the skeletons of patients. Eight patients who were treated with isotretinoin for disorders of keratinization received frequent radiographic evaluations for 4 to 9 years. Seven patients developed multiple hyperostoses at the spine and extremities. Hyperostoses increased in size and number over the course of therapy, although relatively few sites were symptomatic. Hyperostoses typically developed first in the spine and later in the extremities, where both bilaterally symmetric and asymmetric involvement was observed. After 5 years of therapy one patient did not develop hyperostosis. In a group of nine patients who received a relatively high dose of isotretinoin in 1982 for the treatment of acne, two patients developed tiny, asymptomatic hyperostoses. One patient had hyperostoses 1 year after isotretinoin therapy, which remained unchanged 3 years later, whereas the other patient had one hyperostosis 4 years after therapy had been stopped. Although we suspect that these hyperostoses were retinoid induced, they should not be of concern for the patient needing routine isotretinoin therapy for the treatment of cystic acne.

Cyclosporin A, which is a specific immunosuppressive compound, has recently been demonstrated to be of significant benefit in the treatment of psoriasis. Because hyperplasia is a major feature of psoriasis, we have investigated whether this drug acts directly to inhibit keratinocyte growth. We have determined the concentration range of cyclosporin in the epidermis of psoriatic patients undergoing cyclosporin therapy and the effect of this concentration range on the growth of cultured keratinocytes. After 7 days of treatment, psoriatic involved epidermis contained 1.1 +/- 0.3 ng cyclosporin/micrograms DNA. Based on tissue wet weight this is approximately 2.8 micrograms cyclosporin/ml. This value was 10 times that of trough blood samples. On day 3 of treatment, involved epidermis contained 7 times more cyclosporin than scale, while on day 7 this ratio was reduced to 2. This suggests that cyclosporin was initially associated with the lower layers of the epidermis and distributed upward with time. Exposure of adult human keratinocytes, cultured on collagen in the presence of human serum, to cyclosporin (0.1-30 micrograms/ml, 0.4-13-fold higher than lesional cyclosporin) for 2-6 d had no effect on the rate of incorporation of thymidine into DNA. Cyclosporin (1-30 micrograms/ml) also had not effect on the reinitiation of DNA synthesis of quiescent cells subsequent to the reintroduction of serum. In contrast, cyclosporin (1-10 micrograms/ml) inhibited growth of keratinocytes cultured on plastic culture dishes in serum free media (MCDB 153). For a given dose of cyclosporin, cell associated drug was 2-3 times greater in serum free compared to serum containing media. This may contribute in part to the sensitivity of keratinocytes in serum free media to growth inhibition by cyclosporin. These data demonstrate that human epidermis contains a high concentration of cyclosporin after oral administration, and that, under certain conditions, concentrations of cyclosporin within the range found in vivo can inhibit growth of cultured keratinocytes. Because cyclosporin regulates lymphocyte function in vivo and in vitro, the demonstrated antiproliferative effects of cyclosporin on psoriatic keratinocytes in vivo may be due to inhibition of a mononuclear leukocyte-derived keratinocyte growth factor(s) in combination with direct inhibition of keratinocyte growth.

Two cases of diffuse multiple lesions of sebaceous hyperplasia of the face are reported. The results of both medical and surgical therapies had been unsatisfactory. The patients were treated with low dose systemic isotretinoin (13-cis-retinoic acid) which resulted in complete clearing in one case and substantial clearing in the second. We suggest that in those patients cosmetically bothered by diffuse multiple lesions of sebaceous hyperplasia, for which other therapies are unsuccessful or unamenable to the patient, isotretinoin offers a safe, rational therapeutic option.

Pruritus that interferes with sleep is generally diagnosed as having an organic rather than a psychogenic basis. We compared the dermatologic and psychosocial parameters of 79 inpatients with psoriasis with moderate to severe pururitus with (W group; n = 46) and without (NW group; n = 33) wakenings from sleep in association with pruritus. At the time of the patients' admission, compared with the NW group the W group had more severe depressive psychopathologic features (p less than 0.05); were possibly alcoholic, according to behavioral criteria for alcoholism (p less than 0.005); reported a higher daily alcohol consumption (p less than 0.05); and had symptoms suggestive of periodic movements in sleep, or nocturnal myoclonus (p less than 0.05), a sleep physiologic disorder. The two groups did not differ with respect to pruritus severity or other dermatologic parameters at the time of admission or during inpatient treatment. Contrary to the generally accepted criterion for the organicity of pruritus, psychiatric and possibly sleep pathologic factors rather than primary dermatologic factors determined the wakenings from sleep as a result of pruritus.

A 9-year-old girl had the insidious development of lethargy, gingival erosions, and follicular hyperkeratosis with perifollicular hemorrhage. A dietary history disclosed that she consumed only one kind of sandwich and beverage and took no other foods. A skin biopsy specimen was consistent with the diagnosis of scurvy, and marked improvement occurred with ascorbic acid therapy. Although it is an uncommon disorder in the United States, scurvy may occur in persons with prolonged and peculiar dietary habits.

A patient with pustular psoriasis, which was inadequately controlled by high-dose methotrexate and potent topical corticosteroid therapy, was treated with oral methotrexate and the aromatic retinoid etretinate. The patient's psoriasis improved with sustained maximal etretinate therapy and continued high-dose methotrexate therapy. Subsequently, the methotrexate dose was tapered and used of this drug was discontinued. Previously unattainable success in controlling the psoriasis was achieved with continued etretinate treatment. There were no recognizable adverse effects from concurrent therapy. As the methotrexate dose was tapered, the patient noted increased psoriatic arthritic pain, unrelieved at maximal etretinate levels, but improved with indomethacin treatment. Combination therapy with methotrexate and etretinate may be useful in the treatment of severe psoriasis by providing a controlled transition from methotrexate to etretinate therapy alone.

In a double-blind fashion, we compared the effect of topical application of 1% indomethacin cream or 1% meclofenamate cream with the effect of vehicle therapy alone in thirty patients with psoriasis. After 4 weeks' treatment of bilaterally symmetric psoriatic plaques, the indomethacin-treated sides were worse than the vehicle-treated sides in fourteen of twenty patients (p less than 0.01); the meclofenamate-treated sides were worse than the vehicle-treated sides in seven of ten patients (p less than 0.05). We suspect that the nonsteroidal anti-inflammatory drugs contributed to the maintenance of our patients' psoriasis by altering the arachidonic acid transformation cascade.

A malignant dermal cylindroma of the scalp arose from one of multiple long-standing dermal cylindromas in a 76-year-old man with coexisting trichoepitheliomas and bilateral dermal analogue tumors of the parotid gland. The histologic transition from a benign dermal cylindroma to an anaplastic keratinocytic neoplasm was readily apparent. The malignant dermal cylindroma is a rare neoplasm. To our knowledge, the constellation of benign and malignant dermal cylindromas, multiple trichoepitheliomas, and salivary gland neoplasms has not been previously reported.

We monitored the antibody-dependent cell-mediated cytotoxicity of polymorphonuclear leukocytes from 14 patients with psoriasis before and during etretinate therapy. Neutrophils obtained from the patients with psoriasis at pretherapy demonstrated significantly greater cytotoxic activity than control cells. After four weeks of etretinate therapy, the cytotoxicity of neutrophils from the psoriatic patients decreased significantly and was no longer significantly different from the control value (at a 1:1 effector-to-target ratio). The decline in neutrophil cytotoxicity preceded significant clearing of our patients' psoriasis. The reduction in the antibody-dependent cell-mediated cytotoxicity of polymorphonuclear leukocytes from patients with psoriasis occurs early during therapy and may represent one of the mechanisms of action of etretinate.

In a 16-week randomized, double-blind, vehicle-controlled study of topical tretinoin in the treatment of photoaging, all patients applied topical tretinoin to one forearm and vehicle cream to the other. Half of the patients received tretinoin to the face, and half received vehicle cream. All 30 patients who completed the study showed statistically significant improvement in photoaging on the tretinoin-treated forearms, but not on the vehicle-treated forearms. Fourteen of the 15 patients who received tretinoin to the face had improvement in photoaging, whereas none of the vehicle-treated patients' faces improved, a statistically significant difference in response between the two groups. Statistically significant histologic changes were seen in forearm skin treated with tretinoin, but not with vehicle cream. Side effects were limited to irritation of tretinoin-exposed skin.

We review the use of topical tretinoin (all-trans-retinoic acid) in the treatment of aging skin. We have found topical tretinoin capable of improving aged-appearing skin in both a double-blind, vehicle-controlled trial and our clinic patients. The most impressive improvement occurs after application of tretinoin 0.1% cream for 8 to 12 months. Side effects have been limited to a mild, transient, and clinically insignificant burning sensation in the eyes and mild irritation of tretinoin-exposed skin.

Prolonged therapy with retinoid drugs (chemically similar to vitamin A) often results in skeletal hyperostoses, similar to those seen in idiopathic skeletal hyperostosis. Eight patients, aged 5-26 years, with dermatologic disorders were treated with 13-cis-retinoic acid. Skeletal surveys were obtained before and during treatment. In 1 year, six of the eight patients had developed such skeletal hyperostoses in both axial and appendicular regions. The cervical spine was the most common site of involvement. None of the children demonstrated accelerated skeletal maturation. Two of the patients had mild musculoskeletal discomfort during this period. The findings indicate that high-dose 13-cis-retinoic acid therapy may cause skeletal hyperostoses, requiring radiographic monitoring during prolonged periods of treatment. An implication of these observations, relating to the etiology of idiopathic skeletal hyperostosis, is discussed.

Acitretin, a metabolite of etretinate, was given to 38 patients for the treatment of psoriasis. During the first 8 weeks patients received either placebo, 10 mg, 25 mg, 50 mg, or 75 mg of acitretin daily in a double-blind manner. The dosages of 10 mg and 25 mg daily did not achieve any statistically significant improvement in psoriasis over placebo; however, both the 50 and 75 mg dosages were statistically significantly better than placebo. Side effects were primarily mucocutaneous and occurred in most patients receiving 25 mg or more of acitretin daily. After the double-blind period, patients continued treatment in an open fashion until they had received a total of 24 weeks of acitretin therapy. Most patients received 50 mg of acitretin daily, which adequately cleared their psoriasis. After approximately 3 months without acitretin, most patients required retreatment. Subsequent 24-week courses of therapy were generally effective and well tolerated. The most common laboratory abnormalities were elevations of triglyceride, cholesterol, and liver transaminase levels. The efficacy and side effects of acitretin appear to be similar to those of etretinate; the principal advantage of acitretin is its shorter half-life. Although acitretin is a potent teratogen, its rapid elimination makes it a viable treatment for psoriasis among women of childbearing potential.

Minoxidil, a potent peripheral vasodilator used orally for refractory hypertension, has produced hypertrichosis. To determine the efficacy and safety of 1% or 5% topical minoxidil for the stimulation of scalp hair regrowth, we studied fifteen normotensive patients, five with androgenic alopecia and ten with alopecia areata diagnosed clinically and by biopsy, for 12 months. Three of five patients with androgenic alopecia using 5% minoxidil for 12 months noted hair regrowth, ranging from minimally observable hair to an appreciable restoration of larger, pigmented, terminal hair in one patient. Among the patients with androgenic alopecia, regrowth response corresponded to the serum minoxidil blood levels. None of the patients with alopecia areata receiving either 1% or 5% minoxidil noted hair regrowth despite comparable minoxidil blood levels. Improved local absorption of topical minoxidil solution may promote hair regrowth in androgenic alopecia.

A histologic study was designed to evaluate the pilosebaceous unit of the scalp in nonpustular patch- and plaque-stage psoriasis. Punch biopsy specimens from involved and uninvolved areas of 28 patients were sectioned in a horizontal plane for qualitative and quantitative study. All samples were evaluated in a blind mode, and data were analyzed for statistical significance. There was no evidence for alopecia of any type. Sebaceous gland atrophy was a frequent concomitant in the psoriatic lesion, with probable down-sizing of the hair follicle and thinner hair shafts. Paradoxical sebaceous gland atrophy and down-sized hair follicles in psoriasis may be due to possible inhibiting effects of yet unidentified factors produced by the epidermal lesion.

A case of miliaria crystallina occurring with isotretinoin therapy in a patient with lamellar ichthyosis is described. To our knowledge, the association of miliaria crystallina with isotretinoin therapy has not been previously reported.

In our clinical trials of isotretinoin therapy for cystic acne and etretinate treatment of psoriasis, eight patients had growth of excessive granulation tissue. The granulation tissue was found in resolving acne lesions in one patient taking isotretinoin. Among the psoriatic patients taking etretinate, the granulation tissue usually was seen adjacent to nail plates. In two patients, the side effect caused them to stop retinoid therapy. The tissue response did not appear to be related to the daily or cumulative retinoid dose.