Thalidomide and lymphocyte function

282

Correspondence

ultraviolet light, thyroid extract, and surgery.4 However, temporary or partial resolution with recurrence and progression of disease after cessation of treatment is commonly reported (our patient and in References 2-4). The safety, cost-effectiveness, and clinical efficacy of topical 2.5% selenium sulfide lotion for corifluent arid reticulated papillomatosis have been demonstrated in this report. We recommend a clinical trial with this medication prior to the administration of systemic ketoconazole or etretinate. Stephen J. Friedman, Captain, Me, USA, and Harold L. Albert. Colonel, MC, USA William Beaumont Army Medical Center Department of Internal Medicine Dermatology Service El Paso, TX 79920-0115 REFERENCES 1. Roberts SOB, Lachapelle JM: Confluent and reticulate papillomatosis (Gougerot-Carteaud) and P ityrosporum orbbiculare. Br J Dermatol 81:841-845, 1969. 2. Kellet JK, MacDonald RH: Confluent. and reticulated papillomatosis. Arch DermatoI121:587-588, 1985. (Letter to Editor.) 3. Bruynzeel-Koomen CAFM, de Wit RFE: Confluent and reticulated papillomatosis successfully treated with aromatic etretinate. Arch DermatoI120:1236-1237, 1984. 4. Hamilton D, Tavafoghi V, Shafer JC, Hambrick GW Jr: Confluent and reticulated papillomatosis of Gougerot and Carteaud. JAM ACAD DERMATOL 2:401-410, 1980. 5. Nagy R, Fairfield JC: Confluent and reticulated papillomatosis. Cutis 29:48-50, 1982. 6. Sheth RA: A comparison of miconazole nitrate and selenium disulfide as anti-dandruff agents. Int J Dermatol 22:123-125, 1983.

P(h)thirus pubis To the Editor: I am sorry I cannot agree with Dr. Parish (J AM ACAD DERMATOL 12:889, 1985). Research in Encyclopaedia Britannica, in books by zoological authorities, and in books on Greek etymology reveals that the correct spelling of the Latin name of the crab louse is "Phthirus," from the Greek BELp (louse). Some writers wrongfully leave out the second h : "Phtirus." J. De Bersaques, M.D., Kliniek Voor Huidzieten Academisch Ziekenhuis, Gent 9000, Belgium

Reply To the Editor: The International Committee on Zoological Nomenclature officially accepted the report of the original de-

Journal of the American Academy of Dermatology

scription of this animal, and the (unfortunately misspelled) name, "Pthirus" pubis. A few years later the author corrected the spelling to "Phthirus" pubis--but it was, by the Committee's rules, too late. When they accept a name, it is cast in concrete, and can never be changed. Hence we have the anomalous situation of Pthirus pubis being the cause of phthiriasis. Harry L. Arnold, Jr., M.D. 450 Sutter St., #1432 San Francisco, CA 94008

Thalidomide and lymphocyte function To the Editor: Our interest in thalidomide\,2 has resulted in a series of experiments investigating its effect on lymphocyte function. Both lymphocyte transformation and immunoglobulin production were tested. Thalidomide (pure powder) was obtained from the manufacturer (Chemie Griinenthal; Rheinland, West Germany). Several methods of solubilizing thalidomide, which is water- and alcohol-insoluble, were employed. Saturated solutions, with the use of phosphatebuffered saline (PBS), distilled water, and culture media (RPMI-1640) as solvents, were prepared by adding 10 mg to 150 mg thalidomide to 50 ml solvent. The suspension was filtered after 3 minutes of shaking or filtered after various physical procedures, including heating to temperatures between 37° Cand 75° C for 2 to 24 hours. Nonaqueous solutions of thalidomide were prepared with 50% pyridine, 1 N sodium hydroxide, and dimethyl sulfoxide (DMSO) and then diluted with PBS or culture media. Concentration of thalidomide was determined spectrophotometrically by measuring absorbance at 300 nm. 3 In addition, thalidomide was incubated with sheep liver microsomes to determine if metabolites produced by the microsomal activation system were inhibitory to lymphocyte function. 4 Human mononuclear cells were obtained and the effect of thalidomide on lymphocyte transformation to phytohemagglutinin (PHA) , concanavalin A (ConA), pokeweed mitogen (PWM) and mixed lymphocyte culture (MLC) was investigated with the use of standard technics. 5 ,6 The effect of thalidomide on immunoglobulin biosynthesis was investigated by measuring in vitro production of IgG by PWM-stimulated lymphocytes using standard enzyme-linked immunosorbent assay (ELISA) technics.? Overall, we were unable to demonstrate any evidence of decreased transformation to mitogens or a consistent decrease in IgG production by lymphocytes in the presence of thalidomide. Metabolites of thalidomide pro-

Volume 14 Number 2. Part 1 February, 1986

duced by incubation of drug with sheep liver microsomes also did not inhibit lymphocyte function in the systems we tested. As discussed by Barnhill et al 8 in their recent paper, thalidomide is beneficial in disease processes in which lymphocytes appear to playa major role. Although a few studies have reported in vitro suppressive effects of thalidomide or soluble thalidomide derivatives on lymphocytes,9.1o we were unable to demonstrate any effect of thalidomide on lymphocyte function in the systems we tested.

Iris K. Aronson, M.D., Lisa Weber, MD., Dennis West, M.S., and Cunera Buys, M.S. Department of Dermatology University of Illinois at Chicago 808 South Wood St., Chicago, IL 60680 Anthony Reder, M.D., and Jack Antel, M.D. Department of Neurology, University of Chicago 950 East 59th St., Chicago, IL 60637 REFERENCES 1. Aronson IK, Yu R, West DP, et al: Thalidomide-induced peripheral neuropathy. Arch Dermatol 120: 1466-1470, 1984. 2. van den Broek H: Treatment of prurigo nodularis with thalidomide. Arch Derrnatol 116:571-572, 1980. 3. Schumacher H, Smith RL, Williams RT: The JTletabolism of thalidomide: The· spontaneous hydrolysis of thalidomide in solution. Br J Pharmaco125:324-337, 1965. 4. Braun AG, Dailey JP: Thalidomide metabolite inhibits tumor cell attachment to concanavalin A coated surfaces. Biochem Biophys Res Commun 98:1029-1034, 1981. 5. Antel JP, Oger J, Dropcho E, et al: Reduced T lymphocyte cell reactivity as a function of human aging. Cell Immunol 54:184-192, 1980. 6. Burns JB, Antel I, Haren JM, Hopper IE: Human T cell lymphoma with suppressor effects on the mixed lymphocyte reaction (MLR). Functional in vitro lymphocyte analysis. Blood 57:642-648, 1981. 7. Rosenkoetter M, Reder AT, Oger JJF, Antel JP: T cell regulation of polyclonally induced immunoglobulin secretion in humans. I ImmunoI132:1779-1783, 1984. 8. Barnhill RL, Doll NJ, Millikan LE, Hastings RC: Studies on the anti-inflammatory properties of thalidomide: .~f­ fects on polymorphonuclear leukocytes and monocytes. J AM ACAD DERMATOL 11:814-819, 1984. 9. Roath S, Elves MM, Israels MCG: Effect of thalidomide and its derivative on human leukocytes cultured in vitro. Lancet 1:249-250, 1963. 10. Coulson AS, Summers LJ, Lindahl-Kiessling K, et al: The effect of two soluble thalidomide derivatives on lymphocyte stimulation. Clin Exp Immunol 27:241-247, 1970.

Reply To the Editor: We are pleased to respond to the letter by Aronson et al. Their findings are of interest even though there

Correspondence

283

are insufficient details for us to make a totally informed response. We suggest that the difference in results could be the result of several factors. The preparation of the thalidomide is perhaps the first area of difference. The I normal sodium hydroxide hydrolizes the drug, resulting in at least twenty-three different products that may have little or no activity in biologic systems. Dimethyl sulfoxide (DMSO) similarly raises the pH again with the same results. Further, the half-life of thalidomide at the presumed pH is On the order of 3 \/2 hours, and therefore at the end of 3 or 6 dass the preparation may be totally devoid of any biologic activity from the residual thalidomide materials. Recently in Leprosy Review! we showed that the OKT4 helper/inducer lymphocyte is the most likely target cell for thalidomide. Additionally, data have shown the effect of thalidomide on de novo IgM synthesis to T-dependent antigens, as reported in the Scandinavian Journal of Immunology by Shannon of our group 3 or 4 years ago. 2 ,3 I think we can summarize the difference in results (again presumed only because of the lack of details in Aronson's letter) as being the result of differences such as technic and antigen preparation. Clearly the biologic effectiveness of thalidomide is still not completely dissected. Its broad clinical usefulness mandates continued studies by both of our groups and any other interested parties such as Dr. Aronson's.

Larry E. Millikan, M.D., and Robert C. Hastings. M.D., PhD. Department of Dermatology, Tulane University 1430 Tulane Ave., New Orleans, LA 70Il2 REFERENCES 1. Gad SM, Shannon El, Krotoski WA, Hastings RC: Tha-

lidomide induces imbalance in T-Iymphocyte subpopulations in the circulating blood of healthy males. Lepr Rev 56:35-39, 1985. 2. Shannon EJ, Miranda RO, Morales MI, Hastings RC: Inhibition of de novo antibody synthesis by thalidomide as a relevant mechanism of action in leprosy. Soand J Immunol 13:553-562, 1981. 3. Hastings RC: Kellersberger Memorial Lecture 1979. Immunosuppressive/anti-inflammatory thalidomide analogues. Ethiop Med J 18:65-71, 1980.

Chalazion curets for dermatophyte specimens To the Editor: In addition to using the dermatologic curet for obtaining scrapings for cultures of dermatophyte infections and potassium hydroxide (KOH) preparations, as discussed in "Curets for Dermatophyte Cultures" (J AM ACAD DERMATOL 12:728, 1985), I have also been using a small chalazion (spoon curet) to obtain scrap-