G. Zina

Beneficial effect of 15% azelaic acid cream on acne vulgaris

Patients treated with azelaic acid (15%) cream for chloasma reported simultaneous improvement of acne lesions within the treated areas. This prompted an open study of its effect in cases of acne without chloasma. One hundred patients with acne vulgaris were treated for 3–9 months by twice‐daily application of the cream with significant improvement in every case.

Azelaic acid therapy in disorders of pigmentation

Abstract Azelaic acid (COOH(CH 2 ) 7 COOH), is a medium chain-length saturated, 9-carbon atom dicarboxylic acid, which has recently been shown to have important biologic activities and some useful practical therapeutic applications. It can be obtained by oxidation of fatty acids, such as oleic acid, which are unsaturated in the 9-C position, and in humans it has been reported present in the urine of noncompensated diabetics and of patients with congenital inability to oxidize monocarboxylic acids. 1 During investigations on the causation of the hypochromia in pityriasis versicolor, dicarboxylic acids of chain-length C 6 –C 12 were found to be formed in cultures of Pityrosporum to which unsaturated fatty acids with double bonds in the 6 to 12 positions were added. 2,3 An ascending gradient of competitive anti-tyrosinase activity of the diacids was demonstrated and in another study, 4 damage to melanocytes. Because of these findings, it seemed possible the diacids might be involved in the hypochromia of pityriasis versicolor, and perhaps useful in the topical treatment of hyperpigmentary disorders as an alternative to phenolic compounds, such as monobenzoyl ester of hydroquinone, which are alternative substrates of tyrosinase. These latter often produce residual hypochromia of both hyperpigmented and adjacent uninvolved normal skin, which is a disadvantage of their use. The final choice of dicarboxylic acid for original application and investigation fell upon azelaic acid, mainly because it occupies the middle range of anti-tyrosinase activity, is relatively cheap, and more easily soluble and capable of being incorporated into a base cream than those at the higher level of activity. A 15% cream was originally employed, but a 20% one is now standard; occasionally, we have studied the effects of a 35% cream. Early limited open trials established a beneficial effect of the cream on some hyperpigmentary disorders and showed that it had no clinical depigmenting effect on normal skin. 2,5 These preliminary results encouraged further clinical studies extending over the years, and initiated parallel laboratory investigations aimed at elucidating the mechanism of action of azelaic acid. An outline of these will be given first because they provide a background and rationale (often post hoc ) for the clinical use of the diacid.

Thymostimulin therapy in melanoma patients: Correlation of immunologic effects with clinical course

Thirty-two nonmetastatic melanoma patients with low T-lymphocyte values were treated with a thymic extract, thymostimulin (TS) (8 patients), DTIC (8 patients), or surgery alone (16 patients). In the 8 patients receiving TS, active E-rosette (T-Ea) and total E-rosette (T-Et) counts rose to normal levels and there was a significant rise in IgM and IgD receptors. Six out of eight patients treated with TS showed no evidence of metastases after 34 months, while 7/8 patients on DTIC and 13/16 patients on surgery alone developed metastases. Twenty metastatic patients with low T-lymphocyte values received either DTIC plus TS or DTIC alone. Total lymphocyte, T-Ea, and T-Et counts did not increase in either group nor was there a significant difference between the group on DTIC plus TS and the group on DTIC alone. The survival rate of patients on DTIC plus TS did not differ significantly from that on DTIC alone.

The prognostic value of T-lymphocyte levels in malignant melanoma. A five-year follow-up.

Serial immunologic tests (active E‐rosettes = T‐Et; total E‐rosettes = T‐Et; total lymphocytes and null cells) were performed every 3 months for 5 years on 113 melanoma patients. A significant reduction in absolute T‐Ea, T‐Et, null cells, and total lymphocytes was noted in the patients who died, by comparison with those who are still alive. The latter presented a significant reduction in absolute T‐Et only, plus a significant increase in null cells when compared with normals. The 38 patients without metastases, at the end of the study, presented a reduction in T‐Et and an increase in null cells compared with the normals, while the 75 patients with metastases presented a reduction in T‐Et, null cells and total lymphocytes when compared with the patients without metastases and a reduction in T‐Ea, T‐Et, and total lymphocytes when compared with the normals. Null cells show a linear decrease in patients who died and a linear increase in those who survived. A total of 80.2% of patients with a fall in T‐Et displayed metastases usually within 2 to 10 months (mean, 6.8). Patients with normal T‐Ea, T‐Et, and total lymphocyte values showed a significant prolonged survival when compared to those with lower values. In addition, survival seemed to be always a function of immunologic test values, irrespective of the tumor site.

Skin lesions in angioimmunoblastic lymphadenopathy: histological and immunological studies.

Angioimmunoblastic lymphadenopathy with dysproteinaemia is reported (AILD) in four patients with different skin pictures. As the disease progresses two main forms predominate: papulonodular and erythroderma. In all cases the histological picture of the skin mirrors that of the lymph‐node.

A case of acute promyelocytic leukaemia with bullous, haemorrhagic and necrotic skin lesions.

Erythematous-oedematous-bullous skin lesions with necrotic vegetating and haemorrhagic evolution evocating atypical pemphigur or bullous reticulosis, revealed acute promyelocytic leukaemia. Histologically, vesicles and bullae were observed in the Malpighian layer and a dense infiltrate with atypical blasts in the dermis. Atypical promyelocytes (22%) were found in the bone marrow. The cytochemical features of promyelocytes, haemorrhage due to disseminated intravascular coagulation supported the diagnosis.

Relationship between T and B lymphocyte values and prognosis in malignant melanoma

T and B lymphocyte populations were evaluated in 56 patients with malignant melanoma. Active rosettes (T‐Ea) were decreased only in metastatic patients, while the total T population (T‐Et) was decreased in all stages. In addition the metastatic patients presented significant decreases in IgD and IgM subpopulations. An increase in null cells was noted in metastatic patients. Regular controls over a period of 2 years showed that T‐Ea levels were closely linked to the clinical picture. Patients whose values were constant remained cancer free, while a reduction heralded the appearance of clinical and/or radiological signs of metastasis.

The in vitro effect of a calf thymus extract on the peripheral blood lymphocytes of patients with warts

T and B lymphocyte populations were evaluated in forty‐one patients with multiple recurring warts. Active rosettes (T‐Ea) and total T lymphocytes (T‐Et) were significantly decreased.

Active Rosette Test in Cutaneous Lymphoproliferative Disorders

T and B peripheral blood lymphocytes were evaluated in 17 patients with clinical and histological evidence of mycosis fungoides and in ten patients with benign lymphoplasias of the skin. The T subpopulation (T-Ea) characterized by a rapid rosette formation with sheep erythrocytes was also measured in these patients. While both T-total population (T-Et) and T-Ea subpopulation were within the normal range in pseudolymphoma group, a statistically significant decrease was observed in T-Ea and T-Et populations in the mycosis fungoides group. Moreover, the decrease in T-Ea subpopulation was found in all cases under investigation, even when T-Et population was still at the normal levels. A close relation between T-Ea values and clinical status was observed. B and null cells were substantially unchanged in all patients.

In Vitro and In Vivo Effect of Thymostimulin in Melanoma Patients

In addition to skin tests, numerous in vitro methods have been employed for the evaluation of cell-mediated immunity in melanoma. Mitogens such as phytohemagglutinin (PHA), PPD and concanavalin A (ConA) have proved to be of little use in most cases of melanoma.1–5 Also, lymphocyte microcytotoxicity tests, while displaying a certain difference between metastatic and non-metastatic patients, have provided inconsistent results with respect to prognosis.6–9