Dermatologic therapy: December 1987 to December 1988

Therapv Dermatologic therapy: December 1987 to December 1988 Ralph J. Coskey, MD Detroit, Michigan In this article I have reviewed the significant therapeutic advances that have been reported in the English-language literature from December 1987 to December 1988. Clinicians should read the original articles in toto before attempting any new experimental or controversial therapy. (J AM ACAD DERMATOL 1990;22:231-8.)

ACNE AND RELATED CONDITIONS

Erythromycin 2% gel was compared with its vehicle in an 3-week, double-blind study of patients with acne. I At the end of the study 60% of patients treated with erythromycin and 36% treated with the vehicle had good or excellent results. Benzoyl peroxide gel (Benzac W5) was compared with 1% clindamycin phosphate solution (Cleocin T) in the treatment of acne vulgaris in a 12-week study.2 Both agents were effective, but the total number of lesions decreased significantly more with benzoyl peroxide than with clindamycin hydrochloride. Clindamycin phosphate, however, caused less peeling and drying. The authors suggested that the benzoyl peroxide may have been more effective because it has both an antimicrobial effect and a comedolytic effect. Fifteen patients with acne vulgaris were treated with doxycycline, 50 mg/day, and 19 were treated with minocyc1ine, 50 mg twice daily, for 12 weeks. 3 Both regimens were equally effective. Patients with acne who have not responded to oral tetracycline and oral erythromycin can be treated with doxycycline, which is less expensive than minocycline. However, doxycycline frequently causes phototoxicity in the summer, whereas minocycIine rarely causes this problem. Fifty patients with acne were randomly allocated to treatment with either spironolactone, 100 mg/ day, or cimetidine, 1.6 gm/day, for 16 weeks. 4 The clinical severity of the acne and also the sebum exFrom the Dermatology Department, Wayne State University School of Medicine. Reprint requests: Ralph 1. Caskey, MD, 23133 Orchard Lake Rd., Farmington, MI 48024.

16/1/11710

cretion rates decreased significantly with both drugs but more with spironolactone. The authors recommend short-term therapy with spironolactone in patients with severe acne or as an adjunct to more conventional treatment. Severe acne in 120 patients was treated with a 4month course of oral isotretinoin. 5 Ten patients re~ ceived 0.1 mg/kg/day, 80 patients 0.5 mg/kg/day, and 30 patients 1 mg/kg/day. Radiographs of 100 patients were examined; minor spinal hyperostoses were seen in 4 patients and calcaneal hyperostoses in 10. The authors believed that these changes were clinically insignificant because 8% of control sub~ jects had similar changes. The authors did state written retreatment x-ray studies should be considered in patients older than age 35, in those with preisotretinoin therapy symptoms or signs, or in patients who might require a second course of therapy with isotretinoin. ALLERGY

Fifteen adolescent children with severe atopic dermatitis were treated with oral psoralen photochemotherapy (PUV A).6 Initial clearance occurred in 14, and 9 achieved complete remission. Ten children who had been growing poorly resumed normal growth. The major problem with PUVA therapy in children is the possibility of the later development of skin cancers, and thus this therapy should be considered only in very severe cases. A patient with therapy-resistant solar urticaria was treated with terfenadine, 180 mg/day, 1/2 hour before going outdoors.? This treatment prevented development of edema and itching, but blotchy macular erythema still appeared. Before therapy, however, this patient could tolerate only a few min-

231

232

Journal of the American Academy of Dermatology

Caskey

utes of outdoor sunlight and after treatment was able to tolerate a whole day VASCULITIS, VASCULAR DISEASES, AND COLLAGEN DISEASE

Eight patients with livedo vasculItis, who had been unresponsive to therapy, were treated with pentoxIfylhne (Trental), 400 mg three tImes daIly 8 Three healed completely, four noted much Improvement, and one did not change PentoXlfyllme illcreases blood flow through the mIcrocirculation, apparently by mcreaslllg red blood cell flexibilIty and reduclllg blood VISCOSity Other drugs that can be used to treat hvedo vasculitls mclude nIcotlmc aCid, sulfapyndllle, mmldose hepann, aspmn, dlpyndamole, and ntfedlpme In another study9 two patIents were treated with tIclopIdme hydrochlonde, dIpyndamole, and lowdose asptnn with good results Tlclopldrne, which Interferes With platelet aggregation, IS unavailable m the U mted States Cultured allogemc keratillocytes were used to treat 51 patIents With chromc venous or rheumatOId ulcers unresponsIVe to conventIOnal therapy 10 Ulcers healed pnmanly from the edges With thIs therapy The authors beheve the cells may release a growth factor In another study I I topical prostaglandm E2 was used In the treatment of chromc leg ulcers m mne patients The agent was dispersed In hydrocollOId granules and was covered With adheSive COllOId occlusive dressmg (Duoderm) Dressmgs were changed two or three times weekly Ulcers healed completely In eight patients and almost completely III the mnth patIent Treatment lasted 1 to 14 months Twenty patients With cutaneous lupus erythematosus were treated With aCltretm 12 All but five responded to treatment With either total or partial cleanng In seven ofthe patIents, aCltretm was supenor to prevIous treatment With anbmalanal and/or systemic cortIcosterOid agents In five of SIX patIents WIth subacute lupus erythematosus complete c1earmg occurred wlthm 2 to 4 weeks HAIR

Mmoxldl12% was used to treat patients With male pattern hair loss 10 a double-bhnd study 13 Onglnally 225 pahents were evaluated After 48 weeks, mmor-to-dense hair growth was seen III approxImately one thIrd of the patIents These findIngs are comparable to those reported In other studies

In another study l4 3% mmoXldIl was applIed tWice daily for I year to one half the scalp All but two patients had either alopeCia totahs or alopeCia umversalls The mean duration of the harr loss was 11 5 years In thiS study no cosmetIc results were achieved Thymopentm, a synthetIc pentapepttde, the actIVe site of thymopOletm, was gIVen mtravenously to 20 patients With severe alopeCIa areata 15 The drug was admInIstered three tImes weekly for 3 weeks At follOW-Up 6 months later, complete regrowth was seen In seven patients The authors stated that this IS comparable to the 37% response 10 79 patients treated With either topical squanc aCid dlbutylester or dlphencyprone Thymopentm may stimulate suppressor/ cytotoXic T cells that may Inhlblt an autOImmune reaction agamst some haIr follIcles FUNGUS INFECTIONS

Itraconazole, an oral tnazole antIfungal agent unavaI.1able at thIS time In the Umted States, was used to treat 26 patients With dermatophyte mfectlOns of the fingernails and toenails 16 After 9 4 months, cleanng was achieved 10 64% of the fingernails and 73% of toenails The patIents had faIled to respond to gnseofulvill In addition, SIX patients WIth CandIda aibzcans mfectIon of all nal1s were treated With 100 mg/day for a mean penod of 59 months, wlth complete remISSion In all cases In another studyl? five patients With recurrent Tnchophyton rubrum 1Ofection resistant to gnseofulvln and ketoconazole were treated With Itraconazole PatIents were markedly Improved after 3 to 6 months Complete cleanng of toenail mfectlOns, however, was not achIeved When ltraconazole becomes available, It Will proVide a third oral drug that can be used In the treatment of dermatophyte mfectIons Naftmne cream, an allylamine, was found to be effective m the treatment of cutaneous candidIaSIS and also tmea cruns and tInea corpons 18 19 After 2 weeks' therapy 77% of patIents WIth cutaneous candidiaSIS were cured, as were 80% With tmea cruns and tmea corpons PARASITIC DISEASES

Sixty patients WIth 131 leSIOns of cutaneous lelshmamasls were treated With IOtraleslOnal injectIons of sodIUm stIbogluconate antunony (Pentostam) 20 InJections were gIven at 3-day mtervals, 104 patients needed one IOJectIon, 20 needed two, and 6 needed

Volume 22 Number 2, Part 1 February 1990

Dermat%gic therapy: December 1987 to December 1988 233

three. Of the treated lesions 123 healed completely or improved markedly. The authors state that Pentostam normally is used systemically in the treatment of cutaneous leishmaniasis. Many of the side effects seen with systemic therapy were avoided with intralesional therapy. In another study21 two patients with treatmentresistant leishmaniasis were treated with a single intralesional injection of 1.5 mg of bleomycin. The lesions healed in 5 weeks. VIRUS INFECTIONS Twenty-five patients with herpes of the lips or genitalia were treated in a 2-year double-blind controlled study with interferon-beta gel four times daily.22 A reduction in symptoms and severity was noted in 11 of 12 patients. Acyclovir in a dosage of 400 mg twice daily for 1 year was given to patients with recurrent genital herpes simplex virus infection. 23 After completion of the study, 44% of S 19 patients remained free of recurrences, and the mean number of recurrences per year was only 1.8. Treatment was well tolerated and the in vitro susceptibility of the virus did not change during therapy. In another study24 47 patients with recurrent genital herpes were treated for up to 4 years with doses of acyclovir ranging from 200 mg three times daily to 400 mg three or four times daily. The drug was well tolerated and effective during the study. The mean time to recurrences after each course of therapy became progressively longer, and resumption of suppressive therapy was not necessary in 10 patients. Six patients who were seropositive for human immunodeficiency virus (HIY) and who had orat hairy leukoplakia were treated with oral acyclovir, 3.2 gm/day, for 20 days.25 Five showed clinical regression but had recurrences once the drug was stopped. Epstein-Barr virus was demonstrated on immunofluorescence or electron microscopy before treatment but disappeared during treatment. Natural interferon-a was used in two different schedules in the treatment of condylomata acuminata in a randomized, double-blind, placebo-controlled study.26 The drug was injected into lesions twice weekly for up to 8 weeks. Warts were eliminated in 62% of interferon-treated patients but in only 21 % of placebo-treated patients. In another stud y 27 79 patients with biopsy-proved condyloma acuminatum that was refractory to con-

ventional therapy were treated with different interferon preparations. One wart on each patient was injected three times per week for 4 weeks with either placebo or interferon. Of the warts injected with interferon 47% resolved completely compared with 22% of placebo-injected warts. [t is of interest that about one third of interferon-injected warts recurred compared with none of the placebo-injected warts. Both these studies indicate that intralesional interferon may be useful in some cases, but at this time it should not be considered the treatment of choice for venereal warts. l ntralesional bleomycin sulfate was compared with intralesional saline in the treatment of 38 patients with warts. 28 Of 143 warts 97 showed complete resolution after one or two bleomycin injections whereas 2S showed incomplete resolution. The cure rate was 77% for warts on the extremities, 71.4% for periungual warts, and 47.6% for plantar warts. Six patients with acquired immunodeficiency syndrome (AIDS) and associated eosinophilic folliculitis were treated with UVB three times a week. 29 After six to nine treatments, patients reported appreciable relief of itching. Also, in three patients the size and number of lesions decreased. When three patients discontinued therapy, pustules recurred. PAPULOSQUAMOUS ERUPTIONS Twenty-one patients with psoriasis were treated with dithranol for psoriasis, beginning with a 0.5% concentration. 3o This was left on for 20 minutes and then washed off. Concentration was increased to 1%, 2%,4%,8%, 12%, and 16%. Sixteen patients showed clearance in a mean of 19.5 days. Another 27 were treated with UYB and tar baths plus dithranol; in 20 clearing occurred in a mean of 20.3 days. However, 13 of the 16 patients treated with dithranol relapsed in a mean of only 10.6 weeks compared with relapse of 18.9 weeks in 14 of 20 patients treated with UVB and dithranol. The authors concluded that UYB therapy does not improve the clearance of psoriasis but does postpone relapses. The authors used concentrations of dithranol that are not generally available in the United States. It might be worthwhile, however, to consider higher concentrations for the treatment of psoriasis. In another study 31 short-term UYE and coal tar plus dithranol therapy was compared with dithranol alone in a single-blind paired comparison study in 19 patients with chronic plaque psoriasis. The rate of clearance was not enhanced by the addition of coal

Journal of the AmerIcan Academy of Dermatology

234 Coske} tar, but the tar decreased cutaneous IrntatlOn and staInIng In two patients Anthrahn m Lassar's paste was compared With anthralm mOO 125% c1obetasol prOpIonate OIntment 10 the treatment of chromc plaque pSOrIaSIS 32 Those treated WIth the corticosterOId-anthralIn comb1OatIon showed clearance more qUIckly than those treated WIth anthralIn alone, WIth a mean tIme of clearance of 149 days compared WIth 185 days There was no dIfference m the rate of relapses III the two treatment groups, 80% relapsed In 1 year However, staphyloe< ~al follIcuhtls occurred In four of 35 patients In whom the sterOId was used All patIents also were treated WIth dally coal tar baths and suberythema doses of UVB The anthralIn was apphed m concentratIOns of 0 25% to 2% and left on for 24 hours If a combmatlon of coal tar, UVB, and anthralm IS bemg used, It should not be necessary to add c10betasol omtment to the regunen Thus the nsk of folliculItIs would be lessened, and SIde effects from systemIC absorptIon of the cortIcosterOId prepara~ tlOn would be elImmated A noncalclOtroplc vltamm D 3 analogue (MC 903) was evaluated In a double-bhnd placebo controlled study 10 the treatment of 30 patIents WIth psonasls J2 The drug caused a decrease 10 redness, thIckness, and scalIng of lesIons The best results were obtamed In patIents who applIed a concentratIOn of 100 j.Lg/gm, seven of nme patIents had moderate to excellent Improvement In those who used 10 j.Lgj gm, only two of nme had an excellent response after 6 weeks of therapy The authors belIeve that MC 903 mhlbIts the prohferatmg effect of mterleukIn 1 FISh 011 was evaluated m two dIfferent studIes In one study34 28 patIents WIth stable chromc psonasls were treated WIth either 10 fish Oil capsules (MaxEPA) or 10 placebo capsules daIly After 8 weeks of treatment patIents treated WIth the fish oil had sIgmficantly less Itchmg, redness, and scahng than those m the control group In an open study 35 of26 patIents With plaque-type psonasls, 18 capsules of MaxEPA were taken daIly None of the patIents WIth plaque-type psonasls showed Improvement, but a patient WIth generalIzed pustular psonasls markedly Improved In some cases fish 011 may be helpful for psonaSIS ThiS IS espeCIally so 10 patIents treated WIth etretlnate 10 whom elevation of blood lIpIds may be decreased

ACltretm was evaluated 10 the treatment of psonasls m a 24-week study 36 PatIents who were gIven 50 mg/day showed clearance Three months after therapy was stopped, most patIents reqUIred retreatment The most common laboratory abnormalItIes were elevatIOns of serum tnglycendes, cholesterol, and hver transammase levels The advantage of acItretm over etretmate IS that It has a much shorter half-hfe In another study37 175 patIents WIth severe psonaSIS were treated WIth eIther aCltretln or etretmate Doses of 10, 25, or 50 mg of aCltretm or 50 mg of etretmate were used Complete remiSSions occurred only 10 those receIvmg the hIgher doses In a double-blmd study38 72 patIents With seborrheIC dermatitis were treated once daJiy 10 4 weeks WIth eIther 2% ketoconazole cream or 1% hydrocortisone cream Of those treated WIth ketoconazole 80 5% responded, 94 4% ill the hydrocortIsone group responded ThIS study confirms that hydrocortIsone cream IS helpful In seborrheIC dermatitIs In patIents m whom the long-term use of topIcal cortIcosterOIds IS unwarranted, ketoconazole (Nlzoral) cream should be strongly conSIdered TUMORS

Nonmelanoma skIn cancers 10 395 patients were treated WIth hqUId mtrogen cryotherapy 39 LeSIOns were treated WIth two 30-second freezes The overall cure rate was 97% SIX of 225 basal cell carcmomas recurred at a medIan tune of 18 months, and one of 34 squamous cell carcmomas recurred 6 months later One of 128 leSIOns of Bowen's disease recurred after 6 months ThIrteen patIents WIth multIple solar keratoses, three of whom also had basal cell carcmomas, and two patIents With multIple basal cell carCInomas were treated WIth etretmate at a dosage of 1 5 mg/ kg for 1 month and then 0 5 mg/kg/day for another 2 months 40 All patients WIth solar keratOSIs showed a decrease 10 the mean area and number of lesIOns, eight showed complete clearance There was recurrence In two patIents after 9 months of therapy The basal cell carcIDomas decreased In sIze but dId not dIsappear Two patIents With arsemcal multiple basal cell carcmomas or the neVOId basal cell carcmoma syndrome were gIven oral IsotretmOIn for 7 to 8 years 41 Treatment WIth I 5 to 025 mg/kg/day prevented new leSIOns In the patient who had arsemcal basal

Volume 22 Number 2, Part I February 1990

Derrnatologic therapy: December 1987 10 December 1988 235

cell carcinomas. One new lesion in the patient with the nevoid basal cell carcinoma syndrome developed during treatment with 1 mg/kg/day, one new lesion with 0.5 mg/day, and five lesions at 0.25 mg/day. After treatment was discontinued, the first new tumor in the patient with arsenical carcinomas developed 17 months later, whereas 29 tumors developed in the patient with nevoid basal cell carcinoma syndrome within 13 months. In a 3-year study42 oral isotretinoin was given to five patients with xeroderma pigmentosum who had a history of multiple basal cell or squamous cell carcinomas. They were given 2 mg/kg/day for 2 years and followed up for an additional year without the drug. These patients had a total of 121 tumors in the 2 years before treatment was started. During the 2 years of treatment with isotretinoin only 25 tumors occurred; thus the average reduction in the number of skin cancers was 63%. After the drug was discontinued, however, the tumor frequency increased by a mean of 8.5 times over the frequency during treatment. In a lO-year PUVA study, 1380 patients were evaluated for non melanoma skin cancers. 43 There was a strong association between the cumulative dose of PUVA and an increased risk of squamous cell carcinoma of the skin. Patients who received more than 260 treatments had an II-fold increase in risk compared with patients who had received 160 or fewer treatments. This increase in risk was noted in patients of all skin types. There also was modest dose-dependent increase in risk for development of basal cell carcinomas in patients who received in excess of 200 treatments compared with those who received fewer than 160 treatments. Sixteen patients, 12 with cutaneous T cell lymphoma, one with Sezary syndrome, one with actinic reticuloid, and two with parapsoriasis variegata were treated with either a new arotinoid alone or a combination of etretinate and PUV A. 44 Of these patients 92% showed a minor to distinct response of skin lesions within 12.6 (± 7.4 weeks); 50% of the skin lesions cleared in 67% of the patients. After the retinoid therapy was discontinued, relapses occurred in all cases within 3 to 10 weeks. There was no difference in the therapeutic response to arotinoid alone or to the combined regimen. In another study45 five patients with advanced cutaneous T cell lymphoma were treated with arotinoid-ethylester (RO 6298) with complete remission in one and partial remission in two.

Seven patients with mycosis fungoides .were treated with recombinant interferon alfa-2a 2 in combination with etretinate, and four were treated with interferon alone. 46 One patient treated with etretinate and interferon showed complete remission and remained clear for 18 months. Six patients experienced partial remission. One patient treated with interferon alone was clinically in complete remission, but a biopsy specimen revealed a pleomorphic skin infiltrate. In this study two patients could not be examined, two stopped treatment as a result of advancement of the disease, and five stopped treatment because ofside effects, although three had partial remission. Four were treated for a total of 12 months. The authors concluded that interferon either in combination with etretinate or alone can induce remission in some cases of mycosis fungoides. Topical mechlorethamine was evaluated in the treatment of early stage mycosis fungoides with 117 patients. 47 The probability of achieving clinical remission within 2 years of treatment was 75.8% in patients with stage I disease, 44.6% with stage II disease, and 48.6% with stage III disease. Complete remission occurred sooner in patients with stage 1. The median time to relapse was 44.5 months. Although hypersensitivity reactions occurred in 58% of patients, only one patient had to discontinue treatment. Patients in whom hypersensitivity reactions developed were desensitized by treatment with weaker concentrations of mechlorethamine and a gradual increase in concentration over time. In this study the probability of survival at 5 years was 89%. Thymopentin in an intn~venous dosage of 50 mg three times a week was used to treat four patients with Sezary syndrome. 48 After 2 months all patients showed reduction in scaling, thickening, erythroderma, and itching. In addition, a reduction in epidermotropism and cellular infiltration was seen, as well as a decrease in epidermal and dermal Langerhans cells. When the drug was discontinued, relapse occurred. Twenty-eight patients with AIDS-related Kaposi's sarcoma were treated with high-dose human recombinant interferon alia-2a, administered subcutaneously daily for 8 weeks. 49 If patients had stable disease or did show a response, the treatment was continued three times a week until either a complete response or progression of the disease occurred. Of the 26 cases that could be evaluated 12 showed a major response; five also had complete responses histologically. The authors found that there was a

236 Caskey slgmficant 10crease 10 OKT4 cells and a decrease In HIV antigen 10 the seven responders In another study50 patIents with AIDS-associated KapoSI'S sarcoma were treated wIth recombmant mterferon-a Eight had a complete or partIal response The mean pretreatment CD4 count for the responders, however, was 399 cells/ml versus 154 cells/ml for nonresponders All five patIents WIth more than 400 CD4 cells/ml before treatment had a slgmficant reductton In tumor, but none of seven With fewer than 150 CD4 cells/ml had a response In addItion, five of the SIX complete or partial responders had a 75% or greater reductton of virus after 12 weeks of therapy A study was done m 307 patIents to determme whether a 1 cm margm was less effective than a 3 cm margm In the treatment of thm ( < 2 mm) pnmary cutaneous melanomas 51 SurvIval rates at 55 months were Similar In both groups VESICULOBULLOUS ERUPTIONS

Cyclosponne was evaluated In the treatment of nrne patients With pemphigus vulgans 52 Of four treated WIth cyclosponne alone, only one showed clearance Four patients resistant to cortIcosterOIds Iffiproved after cyclosporme was added A mnth patient was treated WIth cyclosporrne and corticosterOIds at the same tlffie but dId not respond The authors concluded that cyclosporme alone IS not adequate treatment for the acute phase of pemphIgus but should be added to treatment With corticosterOids PemphIgus vulgans 10 79 patients was treated 10travenously With 100 mg dexamethasone on three consecutIve days and WIth 500 mg cyclophosphamide orally on day 1 only 53 The mtermlttent high dose of dexamethasone was repeated every 2 to 4 weeks, and patients contmued to take oral cyclophosphamide, 50 mg/day Ten patients were lost to follow-up, and two died Of the remammg patients 25 were able to dlscontmue treatment, 25 were still talang cyclophosphamide, 50 mg/day, and 10 were 10 remiSSIOn but recelvmg mtermlttent high doses of dexamethasone and cyclophosphamide, seven stIll had active disease MISCELLANEOUS CONDITIONS

In a 16-week randomized, double-blInd, vehlclecontrolled study54 topical tretmom was evaluated m the treatment of photoagmg In the 30 patients who completed the study, statistICally slgmficant Im-

Journal of the AmerIcan Academy of Dermatology

provement was seen HIstologIC tmprovement was also reported Smce thiS paper was pubhshed, many presentatIons have been made that support the efficacy of tretmom In the treatment of photoagmg of the skm A patient With hypenmmunoglobulm E syndrome, who had recurrent staphylococcal abscesses that were resistant to treatment With antIbiotIcs and surgical dralOage, was treated WIth a 4-month course of Isotretmom 55 Dunng the 6-month followup penod, no further abscesses occurred The authors beheved that the effect might be due to a reductIon III sebaceous gland sIze and actiVity Three patients With chromc aphthous stomatItIs were treated With colchlcme, 0 6 mg three tImes daIly 56 Symptoms decreased, and the stomatltts showed remISSion Wlthm 3 days of cessatIOn of therapy, however, the disease recurred One of the patIents had to dlscontmue therapy because of persistent diarrhea High-dose mcotlllamide (l 5 gm/day) was used 10 the treatment of 15 patIents WIth necrobIOSIS hpoldlca 57 Of the 13 who remamed on the treatment regtmen for 1month, eight had decreased pam, decrease 10 redness, and healIng of ulceratIOn, If present The skm, however, dld not return completely to normal 10 any patient Accordmg to the authors, mcotmarmde also has been reported to be helpful 10 erythema multlforme, erythema elevatum dtlutmum, polymorphous hght eruption, and erythema IOduratum A pattent WIth penanal and vulvar Crohn's diSease showed complete clearance after a 4-month course of metromdazole, 800 mg/day 58 EIght men With severe recessive X-hnked IchthyOSIS were treated With aCltretm (25 mg/day) for 4 months 59 All had marked Improvement, and the benefiCial effects lasted for 4 to 6 weeks after therapy was dlscontmued Four SiblIngs (aged 2 to 11 years) With PapI1lonLefevre syndrome were treated WIth aCltretlO (05 mg/kg/day) for as long as 16 months Complete cleanng of skm and healmg of glOglval pockets occurred A 43-year-old woman With Behs;et's syndrome and pyoderma gangrenosum was treated With hlghdose oral predmsolone and dapsone but dId not respond 61 When thalIdomide was added, rapId healmg of skm lesIOns and mucosal leSions occurred Twenty-two patients With locahzed VitilIgo, 17 segmental and five focal, were treated With autolo-

Volume 22 Number 2, Part I February 1990

Dermatologic therapy: December 1987 to December 1988 237

gous minigrafting. 62 Thirteen showed 90% to 100% repigmentation, whereas two others had partial improvement. In another study63 14 patients with nondermatoma1 and 31 patients with segmental vitiligo were treated with epidermal grafts from suction blisters. The epidermis of the vitiliginous skin was first removed by blistering with PUVA therapy, and then the suction blister roofs were engrafted. Reepithelialization appeared to be complete in 2 weeks, and the skin color became nonnal in appearance in most cases after about 6 months. Repigmentation persisted in most cases of segmental vitiligo, but in nonsegmental vitiligo pigmentation was lost. Twenty-eight patients with vitiligo were treated three times weekly with khellin, a furanochromone, and UVA. 64 Skin phototoxicity did not seem to occur, but repigmentation did. More than 70% repigmentation was achieved in 41 % of the patients who received 100 to 200 treatments. This is similar to the rate of improvement with psoralens. A mild elevation of liver enzymes developed in seven patients during the early treatment phase, and treatment was discontinued. There was no evidence of long-tenn internal or cutaneous toxicity. The authors believe that khellin is less mutagenic and carcinogenic than psoralens.

REFERENCES I. Pochi PE, BagatelJ FK, Ellis CN, et al. Erythromycin 2 percent gel in the treatment of acne vulgaris. Cutis 1988;41: 132-6. 2. Swinyer LJ, Baker MD, SwinyerTA, et at. A comparative study of benzoyl peroxide and clindamycin phosphate for treating acne vulgaris. Br J Dermatol 1988;119:615-22. 3. Harrison PV. Comparison of doxycycline in the treatment of acne vulgaris. Clin Exp Dermatol 1988; 13 :242-4. 4. Hatwal A, Bhatt RP, Agrawal JK, et al. Spironolactone and cimetidine in the treatment of acne. Acta Derm Venereol (Stockh) 1988;68:84-6. 5. Carey BM, Parkin G1S, Cunliffe W 1. Skeletal toxicity with isotretinoin therapy: a clinical radiological evaluation. Br Dermatol 1988; 119:609-14. 6. Atherton Dl, Carabott F. Glover MT, et al. The role of psoralen photochemotherapy (PUVA) in the treatment of severe atopic eczema in adolescents. Br J Dermatol 1988;118:791-5. 7. Rajatanavini N, Bernhard lD. Solar urticaria: trea.tment with terfenadine [Letter]. J AM ACAD DERMATOL 1988;18:574. 8. Sams WM. Livedo vasculitis: therapy with pcntoxifylline. Arch Dermatol 1988;124:684-6. 9. Yamamoto M, Danna K, Shio H, et at. Antithrombotic treatment in livedo vasculitis. J AM ACAD DERMATOL 1988; 18:57-62. 10. Leigh 1M, Purkis PE, Navsaria HA, et at. Treatment of chronic venous ulcers with sheets of cultured allogenic keratinocytes. Br 1 DermatoI1987;117:591-7.

.r

II. Eriksson G, Torngren M, Aly A, et at. Topical prostaglandin E 2 in the treatment of chronic leg ulcers: a pilot study. Br J Dermatol 1988;118:531-6. 12. Ruzicka T, Meurer M, Bieber T. Efficiency of acitretin in the treatment of cutaneous lupus erythematosus. Arch Dermatol 1988; 124:897-902. 13. Civattel, Laux B, Simpson NB, et al. 2% topical minoxidil solution in male-pattern baldness: preliminary European results. Dermatologica 1987;175(suppI2):42-9. 14. Fransway AF, Muller SA. 3 percent topical minoxidil compared with placebo for the treatment of chronic severe alopecia areata. Cutis 1988;41:431-5. 15. Tosti A, Manuzzi P, Gasponi A. Thymopentin in the treatment of severe alopecia areata. Dermatologica 1988; 177:170-4. 16. Hay RJ, Clayton YM, Moore MK, et at. An evaluation of itraconazole in the management of onychomycosis. Br J Dermatol 1988;119:359-66. 17. Hanifin 1M, Tofte SJ. Itraconazole therapy for recalcitrant dermatophyte infections. 1 AM ACAD DERMATOL 1988; 18:1077-80. 18. Zais N, Astorga E, Cordero CN, et al. Naftifine cream in the treatment of cutaneous candidiasis. Cutis 1988;42:23840. 19. Millikan LE, Galen WK, Gewirtzman GB, et al. Naftiflne cream 1% versus econazole cream 1% in the treatment of tinea cruris and tinea corporis. J AM ACAD DERMATOL 1988;18:52-6. 20. Sharquie KE, AI-Talib KK, Chu AC. Intralesional therapy of cutaneous leishmaniasis with sodium stibogluconate antimony. Br J Dermatol 1988;119:53-7. 21. Soyuer U, Aktas E. Intralesional bleomycin therapy for leishmaniasis cutis [Letter] .Arch Dermatol1988; 124: 1571. 22. Glezerman M, Cohen V, Movshovitz M, et al. Placebocontrolled trial of topical interferon in labial and genital herpes. Lancet 1988; I: 150-2. 23. Mertz GJ, Mills J, lones CC, et al. Long-term acyclovir suppression of frequently recurring genital herpes simplex virus infection: a multicenter double-blind trial. lAMA 1988;260:201-6. 24. Straus SE, Crocn KD, Sawyer MH, et al. Acyclovir suppression of frequently recurring genital herpes: efficacy and diminishing need during successive years of treatment. JAMA 1988;260;2227-30. 25. Resnick L, Herbst JS, Ablashi DV, et al. Regression of oral hairy leukoplakia after orally administered acyclovir therapy. lAMA 1988;259:384-8. 26. Friedman-Kien AE, Eron LJ, Conant M, et al. Natural interferon alfa for treatment of condylomata acuminata. JAMA 1988;259:533-8. 27. Reichman RC, Oakes D, Bonnez W, et al. Treatment of condyloma acuminatum with three different interferons administered intralesionally: a double-blind placebo controlled trial. Ann Intern Moo 1988;108:675-9. 28. Amer M, Diab N, Ramadan A, et al. Therapeutic evaluation for intralesional injection of bleomycin sulfate in 143 resistant warts. 1 AM ACAD DERMATOL 1988;18:1313-6. 29. Buchncss MR, Lim HW, Hatcher VA, et at. Eosinophilic pustular folliculitis in the acquired immunodeficiency syndrome: treatment with ultraviolet B phototherapy. N Engl J Med 1988;318:1183-6. 30. Paramsothy Y, Collins M, Lawrence CM. Effect of UVB therapy and coal tar bath on short contact dithranol treatment for psoriasis. Br J Dermatol 1988; 118:783-9. 31. Duhra P, Ryatt KS. Lack of additive effect of coal tar combined with dithranol for psoriasis. Clin Exp Dermatol 1988; 13:72-3.

Journal of the Amencan Acadcmy of Dermatology

238 Caskey 32 Monk BE, Hehir ME, Clcment MI, et al Anthralin-corti costerold combmatlon therapy 10 the treatment of chromc plaque psonasls Arch Dermato1 1988,124 548-50 33 Kragballc K, Beck HI, Sogaard H Improvement of psonaSls by a topical vltamm D J analogue (MC 903) 10 a dou ble-blind study Br J Dermatol 1988,119223-30 34 BlttJner SB, Cartwnght I, Tucker Wr'G, et al A double blind randoffilzed, placebo-controlled tna! of fish Oil In psof1aSIS Lancet 1988,1 378-80 35 Kettler A H, Baughn RE, Orengo IF et al The effect of dietary fish 011 supplementatIon on psoriasIs J AM ACAD DERMATOL 1988,18 1267-73 36 Goldfarb MT, Ellis CN, Gupla AK, ct al ACltrettn Improves psonasls 10 dosc-dependent fashion JAM ACAD DERMATOL 1988,18655-62 37 Gollmck H, Bauer R, Bnndley C, et a1 ACltretm versus etretmate m psonasls cllmcal and pharmacokmetlc results of a German multIcenter study J AM ACAD DERMATOL 1988, 19458-69 38 Stratlgos JD, Antomou C, Katsambas A, et al Ketoconazole 2% cream versus hydrocortisone I % cream In the treatmentofseborrhclcdermatltls J AM ACAD DERMATOL 1988,19850-3 39 Holt PJA Cryotherapy for sian cancer results over a 5 year penod usmg liqUid mtrogen spray cyrosurgery Br J Dermatol 1988,119231 40 40 Hughes BR, Marks R, Pearse AD, et al Chmcal response and tissue effects of etretmate treatment of patients With solar keratOSIs and basal cell carcmoma JAM ACAD DER MATOl 1988,18522-9 41 Peck GL Long-term retinOid therapy IS needed for mam tenance of cancer chemopreventive effect Dermatologlca 1987,175(suppl 2) 138-44 42 Kraemer KH, DIgIovanna JJ, Moshell AN, et al Preven tlon of skm cancer 10 xeroderma plgmentosum With the use of oraI Isotret100m N Engl J Moo 1988,3\8 1633-7 43 Stern RS, Lange R Non-melanoma skm canceroccurnng In patients treated WIth PUVA five to tcn years after first trcatmcnt J Invest Dermatol 1988 91 120 4 44 Mahrle G, Thiele B RetmOids In cutaneous T-celllymphomas Dermatologlca 1987,175(suppl I) 145-50 45 Hotmg E, MeISSner K ArotlnOid-ethylestcr Effectiveness 10 refractory cutaneous T-cell lymphoma Cancer 1988,62 1044-8 46 Thestrup-POOersen K, Hammar R, Kaltoft K, et dl Treatment of mycosIs fungOldes With recombmant Interferon a2a 2 alone and 10 combmatlon With etretmate Br J Dermatol 1988,118811-8 47 Ramsay DL, Halpenn PS, Zclemuch-Jacquottc A Topical mechlorethamme therapy for early stage mycosIs fungOIdes JAM ACAD DERMATOL 1988,19684-91

48 Bemengo MG, Dovetl GC, Meregalh M, et al ImmunomodulatIOn and Sezary syndrome expenence With thymopent1O (TP-5) Br J Dermatol 1988,119207-21 49 DeWIt R, Boucher CA, Veenhof KH, et al ClImcal and Virological effects of high dose recombmant mterferon-a on dlssemmated AIDS-related KapoSI'S Sdrcoma Lancet 21214-7 50 Lane HC, FembergJ, Davey V, et al Antl-retrovual effects of mterferon a 10 AIDS associated Kap
R-n