Journal of the American Academy of DermatologyVolume 30, Number I

Abstracts from the literature

Pearls of wisdom 121

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Topical tretinoin (retinoic acid) therapy for hy­perpigmented lesions caused by inflammation ofthe skin in black patients

Bulengo-Ransby SM, Griffiths CEM, Kimbrough­Green CK, et al. N Engl J Med 1993;328: 1438-43.

Topical tretinoin cream, 0.1%, was investigated fortreatment of postinflammatory hyperpigmentationcaused by acne or eczema in 54 black persons in a40-week, randomized, double-blind, vehicle-controlledtrial. Tretinoin was applied daily to the face, arms, or bothsites in 24 subjects and a vehicle cream in 30 subjects.Response at baseline and 40 weeks was evaluated byclinical, colorimetric, and histopathologic methods. Sig­nificant clinical improvement occurred in the tretinoin­treated group with lightening of hyperpigmented lesionsby 4 weeks. Some improvement in the vehicle-treatedgroup at 24 weeks was attributed to the passage of timeand sun avoidance. Although background normal skinlightened slightly, there was no unacceptable hyperpig­mentation or depigmentation. Contrary to previous re­ports, black patients had less severe or similar side effectswith topical tretinoin than did white subjects in previousstudies.

Elizabeth A. Abel, MD

The pruritus of cholestasis and the opioid system

Jones EA, Bergasa NY. JAMA 1992;268:3359-62.

A 52-year-old woman had pruritus secondary to pri­mary sclerosing cholangitis. She was treated successfullywith naloxone infusions and then by oral administrationof nalmefene. Symptoms consistent with a mild opioidwithdrawal reaction occurred during initiation of nal­mefene treatment. Itching in cholestatic states "may bemediated centrally rather than peripherally."

Jeffrey D. Bernhard, MD

Placebo-controlled trial of essential fatty acidsupplementation in atopic dermatitis

Berth-Jones J, Graham-Brown RAe. Lancet 1993;341: 1557-60.

This was a well-designed, double-blind, randomized,parallel-groups study with three treatment limbs, whichdocuments the lack of effectiveness of evening primrose

oil or evening primrose oil with fish oil for patients withatopic dermatitis.

Jeffrey P. Callen, MD

Effect of dietary supplementation with very longchain n-3 fatty acids in patients with psoriasis

Soyland E, Funk J, Rajka G, et al. N Engl J Med1993;328:1812-6.

This was a well-designed, double-blind, randomizedtrial that documents the lack of effectiveness offish-oil forpsoriasis.

Jeffrey P. Callen. MD

Atypical fibroxanthoma: DNA ploidy analysis of14 cases with possible histogenetic implications

Worrell JT, Ansari MQ, Ansari SJ, et al. ] CutanPathol 1993;20:211-5.

The histogenesis of atypical fibroxanthoma (AFX) andits relation to malignant fibrous histiocytoma (MFH) iscontroversial. Many workers believe that these two disor­ders represent different poles of a spectrum, AFX simplyrepresenting a superficially located form ofMFH whereasothers have proposed that AFX is an inflammatory "re­active" process. In favor of this latter theory is the factthat AFX has a clinical behavior of a benign lesion withonly rare reports of metastasis. Although abundantstudies have documented the aneuploid nature of MFH,few have evaluated the DNA ploidy of AFX. In thisstudy, a ploidy analysis of 14 cases of AFX wasperformed by means of flow cytometry. The authorsfound that 13 or 14 cases of AFX were diploid and notethat, although this is not proof of benignity, it does sug­gest a distinction from MFH because it would beexpected that ploidy analysis of both processes should besimilar if not identical.

Clay J. Cockerell, MD

Antibody deposits in Tzanck smears in pemphigusvulgaris

Verma KK, Khaitan BK, Singh MK. J CutanPathol 1993;20:317-9.

Smears from bases of blisters of several different pri­mary blistering disorders were made and air dried and

122 Pearls ofwisdom

kept in simple storage at room temperature for up to 10days. Slides were then stained with fluorescein-conju­gated anti-IgG and examined with fluorescence micros­copy. Twenty-one of 27 cases of pemphigus vulgarisdemonstrated positive staining of the membrane of acan­tholytic cells, whereas the one case of pemphigus folia­ceus demonstrated similar staining. None of the cases ofsubepidermal blistering diseases stained positively. In 10cases of herpes zoster, although acantholytic cells wereseen on the Tzanck smear, they failed to take upanti-IgG. This technique is excellent in that it is sensitive,specific, and convenient in that the slides may be kept insimple storage and there are no requirements for frozensections.

Clay J. Cockerell, MD

Cutaneous disease and drug reactions in HIV in­fection

Coopman SA, Johnson RA, Platt R, et al. N EnglJ Med 1993;328:1670-4.

Medical records from 684 HIV-infected patients werereviewed. Five hundred forty (79%) had one or more der­matologic diagnoses totaling 2281 diagnoses. One hun­dred eighty-eight cutaneous reactions to drugs werefound. The highest rates of cutaneous reactions were fortrimethoprim-sulfamethoxazole (149), sulfadiazine(200), trimethoprim-dapsone (156), and aminopenicillins(93). The number ofdiagnoses for skin diseases increasedaccording to the stage of disease; they were lowest inpatients around the time of identification of HIV infec­tion and highest in patients with a diagnosis of AIDS.Cutaneous diseases including drug reactions are ex­tremely common in patients with HIV infection, andtheir incidence increases as immune function deterio­rates.

Mark V. Dahl, MD

Changes in interleukin 2 and interleukin 4 pro­duction in asymptomatic, human immunodefi­ciency virus positive individuals

Clerici M, Hakim FT, Venson DJ, et al. J Clin In­vest 1993;91:759-65.

Infection with HIV results in incremental lossof helperT cell function interleukin (IL) and interferon gammathat is present years before CD4 counts fall and isaccompanied by B-cell activation and hypergammaglob­ulinemia. Patients with decreased IL-2 production were

Journal of the American Academy of DermatologyJanuary 1994

studied and showed an increase in IL-4 production. Lossof recall antigen-stimulated responses could be reversedin vitro by IL-4 antibody.

Comment: Increased IL-4 may explain the atopic ten~

dencies seen in early HIV disease that are characterizedby pruritus and staphylococcal infections.

Madeleine Duvic, MD

Subungual melanoma: A clinico-pathologicalstudy of 24 cases

Rigby HS, Briggs Jc. Br J Plastic Surg 1992;45:275-8.

Subungual melanoma is a well-recognized but rela­tively rare variant of acral melanoma. This study sum­marizes the experience of one institution with this entity.In a series of 2323 patients with primary melanoma(spanning 24 years), 282 acral melanomas were identi­fied; of these, 24 were subungual. Thirteen of 14 upperextremity lesions (93%) were on the thumb and 9 of 10lower extremity lesions (90%) were on the great toe.Three patients had in situ melanoma, whereas 21 had in­vasive disease that were Clark level IV or V (range ofBreslowthickness I to 11mm). Three of the patients withlower extremity melanoma had nodal disease (stage II) atthe time of diagnosis. Other histologic features evaluatedincluded melanoma type, degree of pigmentation, degreeof lymphocytic infiltration, degree of regression, andnumber of mitosis per five high-power fields. Only theBreslow thickness, Clark level, and mitosis per fivehigh­power fieldswere statistically significant when comparingpatients alive with no disease and those dead of disease orwith recurrence. This was a well-written reviewof the de­mographics and histologicfeatures of this subtype of ma­lignant melanoma.

Mary E. Maloney, MD

Simultaneous and separated culture of kerati­nocytes and fibroblasts on each side of a collagenmembrane

Mitsuhashi Y, Mikami Y, Mikami H, et al. J Der­matol Sci 1993;5:3-13.

The ability to study reciprocal interactions betweenepidermal keratinocytes and dermal fibroblasts has beenhampered somewhat by the lack of an in vitro model sys­tem. In this report a new cell culture system wasdeveloped, such that normal human keratinocytes are

Journal of the American Academy of DermatologyVolume 30, Number 1

cultured on the upper surface of a permeable collagenmembrane, whereasfibroblasts are grownon the under­surface in an overall culture maintained as "lifted" (i.e.,present at the air-liquid interface). The collagen mem­brane usedwas permeable to peptides of lessthan 30 kd.With the growing of keratinocytes in theabsence and co­presence of fibroblasts, it was demonstrated that fibro­blasts not only enhance keratinocyte proliferation, butalso keratinocyte differentiation. This biphase separatedcell culture systemis relatively easy to establish and is ausefulnewtoolfor investigative skinbiologists interestedin understandingthe cross-talkbetween resident cells oneither sideof the basement membrane zone(i.e., kerati­nocytes and fibroblasts).

Brian J. Nickolo./J, MD, PhD

Postexposure prophylaxis of varicella in familycontact by oral acyclovir

Asano Y, Yoshikawa T, Suga S, et al. Pediatrics1993;92:219-22.

Acyclovir, 40 or 80 mg/kg/day in four divided doses,was administered orally to 25 infants and childrenexposed to chickenpox. The medication was given for 7days, starting7 to 9 days after exposure to the indexcasein the family. Vesicles and fever developed in only 16%and 4%ofchildrentreated with acyclovir, respectively; incontrast, all untreated children developed vesicles and68% had fever. Eighty-four percent of subjects whoreceivedacyclovir had seroconversion.

Amy S. Paller, MD

Oral and gastrointestinal manifestations of epi­dermolysis bullosa

Travis SPL, McGrath lA, Turnbull Al, et al. Lan­cet 1992;340: 1505-6.

The authorsdeterminedthe frequency oforaland gas­trointestinal findings in 246 patients with epidermolysisbullosa.Dysphagia developed in 76%of patients withre­cessive dystrophic disease, 20% of those with dominantdystrophicdisease, 15% of those with junctional disease,and 2% of those with simplex forms. Lingual adhesionsand microstomia wasfound onlyin the dystrophic formsof the disease. Other abnormalities such as caries, dys­plastic teeth, and constipation were alsonoted.

Neal S. Penneys, MD

Pearls ofwisdom 123

Epidermolysis bullosa complicated by squamouscell carcinoma: report of 10 cases

McGrath JA, Schofield OMV, Mayou BJ, et al. JCutan PatholI992;19:1l6-23.

Ten patients with scarring epidermolysis bullosa,mostly generalized recessive dystrophic epidermolysisbullosa, survived to adulthood only to have significantsquamous cell carcinomas. The tumors developed on theextremities in areas of chronic scarring, ulceration, andcrustingthat wereotherwise typicalfor the disease. Sixofthe patients had multiple tumors, many of which wereaggressive and difficult to detect. Metastatic diseaseleading to death occurredin three patients, underscoringthe need for close vigilance and early biopsyof any sus­pect lesions.

Stuart J. Sa/asche, MD

Clinical course of psoriasis in children treated inthe Department of Dermatology, Medical Acad­emy of Lublin, in 1980-1990

Toruniowa B, Kadziela-Wypska G, Urban J. Prze­glad Dermatol 1992;79:273-8. (Polish)

Twohundredtwenty-eightchildren with psoriasis werestudied retrospectively; almost half of the children hadguttate psoriasis. Antibiotictreatment was an importantfactor in shortening the course of the psoriasis, but onlywhen infection was present. All children with psoriasisshould have an orolaryngeal examination to evaluatethepossibility of an symptomaticinfection.

Robert A. Schwartz, MD

N-of-one clinical trials: the practice of environ­mental and occupational medicine

Hodgson M. J Occup Med 1993;35:375-80.

This articlereviews the N-of-oneclinicaltrial conceptand extends the principles to the cause-and-effect ques­tion that arises in sortingout environmental or work-re­lated. contribution todisease. A hypotheticalcase presen­tationis presented, withdiscussion of the methodsused todeterminewhetherthepatient'ssymptoms wererelatedtoworkactivities. Use ofa clinical modelof causation withpower that would help physicians have reasonable cer­tainty about causalrelations wouldbe helpfulfor the pa­tient, for legal inquiries, and for employers becauseran­domizedexposure trials (for example) raise ethical con-

124 Pearls ofwisdom

cerns. The N-of-one clinical trial approach may also beapplicable to evaluating exogenous exposures and skindisease.

Elizabeth F. Sherertz, MD

New concepts about the mast cell

Galli SJ. N Eng! J Med 1993;328:257-65.

The cutaneous mast cell has avoided the limelight caston other inflammatory cells. In this review of the role ofthe mast cell in inflammatory processes, Galli highlightsthe interaction of the mast cell with the neutrophil andeosinophil in IgE-dependent reactions. This mast cell­leukocyte cascade is potentially important in modulatingpersistent inflammatory reactions as well as anaphylacticones.

Alvin R. Solomon, MD

Journal of the American Academy of DermatologyJanuary 1994

Effects of HIV infection on the serologic mani­festations and response to treatment of syphilis inintravenous drug users

Gourevitch MN, Selwyn PA, Davenny K, et al. AnnIntern Med 1993;118:350-5.

Evaluation of a cohort of 50 intravenous drug userswith syphilis, 31 of whom were HIV positive, revealed thefollowing: No link between stage of disease and HIV sta­tus; absence of unusual or fulminant disease and neuro­syphilis in HIV-positive patients; higher nontreponemaltiters in HIV-positivepatients (1:128vs 1:32);predictableresponse to treatment in all seropositive patients evalu­ated (26 of 31) after therapy. HIV infection did not af­fect the course of syphilis-presentation, response totreatment, serologic changes-in this group of intrave­nous drug users.

Comment: This report provides additional evidencethat severe/unusual cases of syphilis are probably excep­tional and that HIV infection usually has little effect onthe course of syphilis and its response to treatment.

Kenneth J. Tomeckl, MD

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