Effectiveness of infliximab in pityriasis rubra pilaris is associated with pro-inflammatory cytokine inhibition.

BACKGROUND: Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease. Recently, the use of anti-TNF-α in treating resistant forms of PRP has been reported. OBJECTIVES: To evaluate the clinical efficacy of infliximab in the treatment of PRP along with the evolution of secretion of some serum cytokines during treatment. METHODS: Patients presenting widespread PRP were included consecutively and treated with infliximab. We compared cytokine profiles (notably CXCL-10 and TNF-α) by ELISA in sera from both patients with PRP and controls (healthy/psoriasis) at the time of diagnosis and after clinical remission (PRP). RESULTS: 4 patients were treated with infliximab and achieved complete remission without any recurrence after treatment ending. The serum level of TNF-α and CXCL-10 was increased at the time of inclusion and normalized after treatment. Analysis of the typical component of the T helper cell 1 (Th1) and Th2 cytokine network did not show modification. CONCLUSION: Infliximab is an effective treatment of PRP. The analysis of the cytokine profile is in agreement with an absence of further recurrence of PRP by an early and unique inflammatory mechanism without significant underlying autoimmunity.

Extremely high parathyroid hormone concentrations associated with pityriasis rubra pilaris and monoclonal gammopathy of unknown significance: a clinical dilemma.

We present a case with extremely high parathyroid hormone (PTH) concentrations in the order of hundred thousands accompanied by dermatological and hematological diseases. After several diagnostic interventions, no malignancy could be demonstrated except monoclonal gammopathy of unknown significance. The dermatological findings were taken to be manifestations of the hematological disease. Since the first serum intact PTH concentration of the patient was found to be higher than 2500 pg/ml, dilution study was performed and found to be 215,977 pg/ml. The high concentration of serum PTH was taken to be falsely high due to assay interference. This concentration was checked from three different paths; a test for linear dilution was performed, the test was repeated with another method and the sample was treated to remove or inhibit interfering substances. The results were compatible with endogenous antibody interference, presumed to be a result of monoclonal gammopathy. The extremely high PTH concentrations were not only due to assay interference, but also secondary hyperparathyroidism, which was evident by the decrease in PTH concentrations with calcium and vitamin D treatments.

Circumscribed juvenile-onset pityriasis rubra pilaris with hypoparathyroidism and brachyonychia.

Circumscribed juvenile-onset pityriasis rubra pilaris (PRP) manifests as well-defined erythematous scaly plaques with follicular keratosis mainly over the elbows and knees. There are several reports of the association of PRP with other conditions. We report a boy with scattered erythematosquamous skin lesions and follicular hyperkeratotic papules since he was 6 years old. Results of a skin biopsy were compatible with PRP. The patient also had hypoparathyroidism and brachyonychia. To our knowledge, this association has not been reported to date, though minor disturbances of calcium and vitamin D metabolism have been mentioned in some disorders of keratinization. We further discuss the epidemiologic, clinical, and pathologic features of PRP; review the conditions associated with brachyonychia; and give a brief discussion about the possible role of calcium metabolism in disorders of keratinization.

Serum parathyroid hormone level is elevated in some patients with disorders of keratinization.

BACKGROUND AND DESIGN: After the chance of observation of an elevated parathyroid hormone (PTH) value in a patient with pityriasis rubra pilaris, the serum PTH level was measured in the next 14 patients seen with disorders of keratinization. Calcium metabolism in three affected patients was then studied in depth. RESULTS: Five of 15 patients had twofold or greater elevations in serum PTH values. The patients had four different disorders of keratinization: bullous congenital ichthyosiform erythroderma (two patients); lamellar ichthyosis (one patient); pityriasis rubra pilaris (one patient); and ichthyosis linearis circumflexa (one patient). At least one other patient with each diagnosis had normal PTH values. Two of three patients who were studied further had clear evidence of increased, biologically active PTH, consistent with secondary hyperparathyroidism. An elevated PTH level spontaneously became normal in one patient, and in a second patient it became normal with a high-calcium diet. CONCLUSIONS: These data provide the first indication that patients with various disorders of keratinization have an increased risk for secondary hyperparathyroidism. The exact prevalence, origin, and physiologic significance of this finding remain to be elucidated.

Isotretinoin treatment of pityriasis rubra pilaris.

Five patients with pityriasis rubra pilaris were treated with isotretinoin from September 1982 through 1985. Isotretinoin at an average dose of 1.16 mg/kg/day for 16 to 24 weeks caused complete or almost complete clearing in four of the five patients.

Pityriasis rubra pilaris, vitamin A and retinol-binding protein: a case study.

A patient with longstanding erythroderma and decreased sweat secretion due to the classical adult form of pityriasis rubra pilaris is described. The patient did not respond to oral megadoses of Vitamin A, even though a large increase of liver content of Vitamin A was demonstrated. Retinol-binding protein levels in serum of this patient and his relatives were normal. Danazol (Danatrol, Winthrop) therapy caused an increase of retinol-binding protein level, but clinical improvement did not occur.

Further experience with toxic vitamin A therapy in pityriasis rubra pilaris.

A patient with short-duration pityriasis rubra pilaris was successfully treated with high-dose, toxic vitamin A (retinol), but the disease subsequently recurred in new areas. Serum levels of vitamin A were highest four hours after treatment and returned to the base level within twelve hours. Fasting blood levels of vitamin A during treatment increased to five times the pretreatment level. Ultrastructural changes in the keratinocytes were notable vacuolation, granularity of the cytoplasm, and a decrease in tonofilament masses, all indications of the cellular effect of the vitamin A. We believe that patients with long-duration pityriasis rubra pilaris should be considered for this treatment.

Pityriasis rubra pilaris and and retinol-binding protein.

Serum levels of retinol-binding protein (the specific carrier of vitamin A) were measured in eleven patients with pityriasis rubra pilaris and in some of their close relatives. The level of retinol-binding protein was markedly reduced in every patient, and in some of the relatives. It is postulated that defective synthesis of retinol-binding protein is a biochemical marker for pityriasis rubra pilaris, probably transmitted as a Mendelian dominant.

Plasma vitamin A levels in the hyskeratoses.

No significant difference was found between the plasma vitamin A levels of patients with dyskeratoti skin disease and those of comparable control subjects.