Fitzpatrick RE [Univ of California, San Diego]
Treatment of Inflamed Hypertrophic Scars Using Intralesional 6-FU
Dermatol Surg 25: 224 - 232, 1999, Pg 165.
Intralesional injections of 5-FU in a concentration of 50 mg/ml were administered in doses ranging from 2 to 50 mg.
Mixing 0.1 ml of Kenalog [Westwood Squib, Buffalo, NY] and 0.9 ml of 5-FU in the same syringe caused less pain and had greater efficacy.
It was rare for a scar to not respond favorably. Scars with the greatest response were typically red, the most inflamed, the most symptomatic, and most firmly indurated. The first signs of response were typically reduced pain and itching, followed by softening of the scar, then flattering and decreased redness. Hypertrophic scars were more responsive than keloids.
The use of intralesional injections alone or in combination with Kenalog with pulsed dye laser is safe and effective in the treatment and prevention of hypertrophic scars and some small, isolated keloids.
Cheung TW, for the TLC D-99 Study Group [Mount Sinai School of Medicine, New York; et al]
AIDS-Related Kaposi’s Sarcoma: A Phase II Study of Liposomal Doxorubicin
Clin Cancer Res 5: 3432-3437, 1999
Doxorubicin in a liposomal combination, [ the latter derived from egg phosphatidyl choline – cholesterol liposomes ] has been useful as TLC D-99 in the treatment of Aids associated Kaposi’s sarcoma. It was diagnosed histologically in 40 men [median age 35 years] suffering from Aids, and comprising the II phase of this study. They were divided into a stable of group of 21 patients and another of 19 not categorized as stable. The former received a dose of 20mg/m2 and the latter 10 mgm/m2 intravenously as a drip over a period of 1 hour every 2 weeks.
A stable state was maintained by 13 patients in each group. The group on 20 mgm/m2 showed a better response. The commonest side effect was neutropenia. Total clearance was not achieved.
Rezza G, for the Italian Seroconversion Study [Istituto Superiore di Sanita, Rome, Italy; et al]
Human Herpesvirus 8 Seropositivity and Risk of Kaposi’s Sarcoma and Other Acquired Immunodeficiency Syndrome -Related Diseases
J Natl Cancer Inst 91: 1468-2474, 1999
336 patients of AIDS were studied to determine if a prognostication for development of Kaposi Sarcoma [KS] could be made. HHV-8 and HIV have been held responsible for KS evolution. The present study between 1983 and 1996 reports on HHV-8 antibody levels and KS expression. Epstein-Barr virus antibodies were looked for.
21 cases of KS were detected in a median period of 5-8 years. A titer of 1 in 125 or higher suggests that the subject is at a greater risk of developing KS especially beyond 7 years of infection. Of the 21 patients, 19 were homosexuals, 1 was heterosexual and 1 who had KS but not HHV-8 infection was a homosexual.
Thus longer the duration of HHV-8 infection in the milieu of Aids and background of homosexuality the greater the incidence of KS.
Boden D, Hurley A, Zhang L, et al [ Rockefeller Univ, New York; AIDS Healthcare Found,
Los Angeles; ViroLogic Inc, South San Francisco]
HIV-1 Drug Resistance in Newly Infected Individuals
JAMA 282: 1135-1141, 1999
Long term use of antiretroviral drugs as expected would induce resistance in the virus. 80 newly infected subjects were studied. Drug resistance was observed in 13, 10 to a nucleoside reverse transcriptase inhibitor [NRTI] 2 to a protease inhibitor and 6 to a non-NRTI. Three were multidrug resistant.
Despite good effects in reducing morbidity of the disease, a serious problem as has occurred in the management of other bacterial diseases, should be anticipated.
Little SJ, Daar ES, D’Acquila RT, et al [ Univ of California, San Diego; Univ of California, Los Angeles; Massachusetts Gen Hosp, Boston; et al]
Reduced Antiretroviral Drug Susceptibility Among Patients with Primary HIV Infection
JAMA 282: 1142-1149, 1999
It is not known how often HIV resistant to one or more antiretroviral [ARV] drugs causes new infections.
Acute and early infections in subjects were studied between the years 1989 and 1998. Plasma samples were taken from 141 such cases in 5 different centres. Drug effect on the virus were studied. A 2.5 times reduction of effect was the standard used. Five samples showed reduction in more than this level to at least 1 nucleoside reverse transcriptase inhibitor [NRTI], 2 revealed 10 times reduction and 24 samples to a non-NRTI . Only 1 showed a 10 > times reduction. A single mutation in the resistant group T215Y was discovered in 36 samples.
In HIV infections resistance 2.5 and 10 times range are common. Testing for resistant virus strains is advised in areas of high prevalence of uncontrollable AIDS.
Eckert DM, Malashkevich VN, Hong LH, et al [ Howard Hughes Med Inst, Cambridge, Mass]
Inhibiting HIV-1 Entry: Discovery of D-Peptide Inhibitors That Target the gp41 Coiled-Coil Pocket
Cell 99 : 103-115, 1999
Prevention of HIV-1 virus from entering a cell seems logical. Short chains of D-amino acids resistant to proteolysis and designated 1QN17 act by attaching to the gp41 region of the virus. These newly discovered chains thus prevent the virus from using such proteins on the cell membrane of the host. It is of interest that the agent can be given by mouth as a tablet.
Hazuda DJ, Felock P, Witmer M, et al [Merck Research Labs, West Point, Pa]
Inhibitors of Strand Transfer That Prevent Integration and Inhibit HIV-1 Replication in Cells
Science 287: 646-650, 2000
In the management of HIV-1 infection drugs acting on reverse transcriptase and protease enzymes of the virus have been relied upon. The development of resistance constitutes an important reason for search of alternatives.
HIV integrase is used by the virus to allow its DNA to be introduced into the cell genome, a step necessary for it to replicate. This article introduces diketo acids L-731,988 and L-708,906 to prevent such strand integration.
At the moment it is in the experimental stage.
Martinez E, Gatell J, Moran Y, et al [ Hosp Clinic, Barcelona]
High Incidence of Herpes Zoster in Patients with AIDS Soon After Therapy with Protease Inhibitors
Clin Infect Dis 27: 1510-1513, 1998
193 HIV-1 patients of Aids being treated with a nucleoside analogue reverse-transcriptase inhibitor [NRT1] were followed up. Those with CD4+ at base line levels were given a protease inhibitor in addition.
During a median of 64 weeks, 14 patients [7%] developed a first or recurrent episode of herpes zoster most often in the first 4 and 16 weeks, after starting the protease inhibitor. The high CD8+ counts noticed at the end of the first month may be a mechanism of this precipitation of herpes zoster.
The risk of this complication is calculated to be twice that expected in the non protease inhibitor group.
Breton G, Fillet A-M, Katlama C, et al [ Hopital Pitie Salpetriere, Paris]
Acyclovir-Resistant Herpes Zoster in Human Immunodeficiency Virus Infected Patients: Results of Foscarnet Therapy
Clin Infect Dis 27: 1525-1527, 1998
Eighteen patients of isolation confirmed varicella-zoster virus [ VZV] infection manifesting as herpes zoster in HIV-1 positive subjects are reported. They were resistant to acyclovir-therapy. Thirteen subjects received IV foscarnet in a dose of 100 mgm/kg twice a day. In one patient the dose had to be reduced to 120 mgm because of hypocalcemia lesion clearance was achieved in ten patients five relapsed with recurrence in the same dermatomes in a little over three months after treatment. Three of these cleared with acyclovir or foscarnet. Of the total of 16 followed for a median of 8 months 4 died of visceral effects of VZV infections. Normally the drug is used in a dose of 40 mgm/Kg thrice a day or 60 mgm/kg twice a day. It is important to note that patients tolerated the larger dose. Message of the paper is “acyclovir resistant herpes zoster is a serious in patients of Aids.”
EI Hachem M, Bernardi S, Pianosi G, et al [ Bambino Gesu Children’s Hosp and Health Research Inst, Rome
Mucocutaneous Manifestations in Children With HIV Infection and AIDS
Pediatr Dermatol 15: 429-434, 1998
In a 5 year period with a follow-up of 31 months [average], 166 HIV positive children in an average age group of 14.8 months, were taken for study. Of these, 81 children became HIV negative spontaneously indicating lack of infection. Of the remaining 85 HIV-positive children, 76 revealed a minimum of 1 skin effect. These comprised infestations, infections, and inflammatory diseases. They increased as the immune depletion progressed. Despite tumour rarity in children Kaposi sarcoma was diagnosed in one child.
This article highlights the importance of seroreversal in infants, rare occurrence of tumours in childhood HIV infection and reports a single possible Kaposi sarcoma. Candidosis topped all other infections.
Fitzpatrick RE (Univ of California, San Diego)
Treatment of Inflamed Hypertrophic Scars Using Intralesional 5-FU
Dermatol Surg 25: 224-232, 1999
Nine-year experience of use of 5-Fluorouracil by itself and in conjunction with low dose intralesional corticosteroids plus pulsed dye laser therapy is reported. 1000 patients were treated over nine years period.
It is safe and effective treatment for such scars and prevention of hypertrophic scars and in small isolated Keloids. It controls angiogenesis, suppress fibroblast activities and endothelial growth factor expression.
Rosen T, Schell BJ, Orengo I [Baylor College of Medicine, Houston]
Anti inflammatory Activity of Antifungal Preparations
Int J Dermatol 36: 788-792, 1997
This study compares the results of several antifungal creams with 2.5% hydrocortisone to determine their anti-inflammatory properties. UVB induced erythema of non-exposed sites were used for evaluation.
1% terbinafine, 1% ciclopirox olamine, and 1% naftifine hydrochloride were shown to possess anti-inflammatory effects that were greater than hydrocortisone. Other creams used were 2% ketoconazole, 1% oxiconazole nitrate and 1% econazole nitrate. These were less effective.
The use of an antifungal agent with anti-inflammatory activity thus takes care of the inflammatory component of fungal infections. Side effects of a steroid of the combination preparation are thus avoided.
Bornstein J Heifetz S, Kellner Y, et al [Carmel Med Ctr, Haifa, Israel]
Clobetasol Dipropionate 0.05% Versus Testosterone Propionate 2% Topical Application for Severe Vulvar Lichen Sclerosus
Am J Obstet Gynecol 178: 80-84, 1998
20 postmenopausal women were treated with 0.05% clobetasol propionate and 20 with 2% testosterone propionate. Mean age group was 64 years and follow up was carried out at three months and 1 year, between 1988 and 1993. Short and long terms were thus covered.
Clobetasol was more effective than testosterone. Side effects such as skin atrophy [as would be expected with a corticosteroid ointment] were not seen. Patient compliance was better with clobetasol than with testosterone. One in the steroid group and six in the testosterone had side effects.
Burks AW, James JM, Hiegel A, et al [Univ of Arkansas, Little Rock; Arkansas Childrens Hosp Research Inst, Little Rock]
Atopic Dermatitis and Food Hypersensitivity Reactions
J Pediatr 132: 132-136, 1998
This is a double-blind, placebo-controlled study of 165 subjects of atopic dermatitis [AD] between the ages of 4 months and 21.9 years. On the basis of prick test positivity to common foods elimination and challenges were performed. Foods included milk, eggs, peanuts, wheat, soy, fish and tree-nuts. 98 subjects were positive to one food on prick testing. Of these 64 revealed a positive response on challenge.
The importance of this article lies in its bringing out necessity of testing for commonly used foods in the management of AD. Foods to be tested for, depends on the food habits of the individual hence the value of dietary amnesis.
Levi F, La Vecchia C, Te V-C, et al [ Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Registre Neuchatelois des Tumeurs, Neuchatel, Switzerland; Universita degli Studi Milano, Italy]
Incidence of Invasive Cancers Following Basal Cell Skin Cancer
Am J Epidemiol 147: 722-726, 1998
A total of 11,878 basal cell carcinoma subjects between the ages of 15 years and 100 years were followed up for 20 years. All were confirmed by histology. In the period of follow-up lip cancers, melanomas, squamous cell carcinomas and lymphomas other than Hodgkins were fond to be more common.
Once an individual has had a basal cell carcinoma he should be examined for other skin cancers and lymphomas, as a long term follow up measure.
Kang S, Fisher GJ, Voorhees JJ [Univ of Michigan, Ann Arbor]
Photoaging and Topical Tretinoin : Therapy, Pathogenesis, and Prevention
Arch Dermatol 133: 1280-1284, 1997
Dry, rough finely wrinkled and dyspigmented skin with loss of normal tension characterize skin aging. Such changes developing on sun exposed skin constitute photoaging. They result from loss of collagen in the upper dermis induced by metalloproteinases, a group of enzymes causing collagen breakdown. Ultraviolet light especially the B component [UVB] is responsible for this effect.
Application of Tretinoin cream reverses such damage. The earliest sign of improvement is reduction of wrinkling.
Egan CA, Rallis TM, Meadows KP, et al [ Univ of Utah, Salt Lake City]
Low-dose Oral Methotrexate Treatment for Recalcitrant Palmoplantar Pompholyx
J Am Acad Dermatol 40: 612-614, 1999
Pompholyx is a vesicular to bullous eruption of the palms and soles possibly related to eczema often needing large doses of prednisone to control it.
Side effects of therapy often outweigh usefulness. 5 patients successfully treated with methotrexate are referred to.
A single case report brings this out well. Man 39 years had gross restriction in work capacity due to long standing pompholyx. Control needed 60 mgm of prednisone in 2 divided doses and local clobetasol. The condition improved but in 4 weeks the blood pressure was recorded as 200/110 mmHg. Methotrexate in a dose of 15 mgm/wk was introduced to allow of prednisone reduction. With gradual withdrawal of prednisone, it was found that methotrexate could replace it totally. The patient is controlled thus; no corticosteroid ointment is being used.
Monitoring liver function and looking for drug interaction are mandatory with methotrexate therapy.
Atopic Eczema and Domestic Water Hardness
McNally NJ, Williams HC, Philips DR, et al ( Univ of Notingham, Univ Park, England; Queen’s Med Centre, Nottingham, England; City Hosp, Nottingham, England )
Lancet 352: 527-531, 1998
The causes of atopic eczema are not clear. It is believed that environmental factors play a role. One possible risk factor could be an exposure to domestic hard water. The present ecologic study examined the association between hard water exposure and prevalence of eczema in children.
It was observed that exposure to hard water at home was a risk factor for eczema in primary school children. This effect appears age related because it does not appear in secondary school children.
( How do you explain this association between water hardness and eczema ? It could be that more soap and shampoo is required to obtain lather in hard water. Increased exposure to soap and their additives can have an irritant effect on the skin. )
Atopic Dermatitis Symptoms Decreased in Children Following Massage Therapy
Schachner L, Field T, Hernandez – Reif M, et al (Univ of Miami, Fla)
Pediatr Dermatol 15: 390-395, 1998
This study included 20 children with atopic dermatitis who were massaged by their parents for 20 minutes daily for one month and treated with standard topical care. The controll group received only standard topical care.
Immediately after massage therapy sessions, the affect and activity levels improved significantly. Lower anxiety levels were reported in these children with significant clinical improvement, including redness, scaling, lichenification, and pruritus.
Thus massage therapy could be a useful adjunct treatment for atopic dermatitis. Depression, stress, and anxiety have been correlated with the severity of atopic dermatitis, which may cause negative effects on the immune system. Massage therapy could reduce stress and anxiety and improve peripheral blood supply and also the tendency to itch and scratch.
U. Chaudhari, P. Romano, et al
Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomized trial.
Lancet. Vol.357, June 9, 2001, pg.1842
Currently available treatments for moderate to severe psoriasis are either incompletely effective in some patients or are associated with toxic effects. Since TNF-a is thought to have a role in pathogenesis of psoriasis, the authors did a double-blind, randomized trial to assess the clinical benefit and safety of infliximab – a monoclonal antibody against TNF-a.
Patients receiving infliximab as monotherapy had a high degree of clinical benefit and rapid time to response in the treatment of moderate to severe plaque psoriasis compared with patients who received placebo. These findings suggest that TNF-a has a major role in the pathogenesis of psoriasis. There were no serious adverse events and infliximab was well tolerated. Infliximab was used in the doses of 5mg/kg and 10mg/kg IV at weeks 0, 2 and 6, and patients were assessed at 10 weeks.
Mills CM, Llwelyn MB, Kelly DR, et al (Univ of Wales, Cardiff)
A Man Who Pricked His Finger and Smelled Putrid for 5 Years
Lancet 348: 1282, 1996
This paper describes a man (29 years) presenting with a malodorous erythematous finger developing after a chicken bone injury.
Clostridium novyi was cultured from the initial skin biopsy. Three others were isolated from the arm and chest.
He was immunologically normal. After treatment with antibiotics and hyperbaric oxygen the finger improved but the putrid odor persisted.
The authors suggest a blind spot in the immune system allowing skin colonization by Clostridia.
They want to know if anyone has seen this and how to treat this condition.
Isabelle Marcil, Robert S. Stern
Squamous-cell Cancer of the Skin In Patients Given PUVA and Ciclosporin: Nested Cohort Crossover Study
Lancet, Vol.358, September 29, 2001, Pg.1042
Immunosuppressive treatments have been associated with an increased risk of skin cancer, especially in patients who have had organ transplants.
Authors have aimed to assess the risk of skin cancer in patients taking ciclosporin who had been exposed to psoralen and ultraviolet- A light (PUVA) and other treatments for severe psoriasis.
There were 28 participants. In the 5 years before first use, 6 of 28 (21%) ciclosporin users developed a total of 20 squamous cell cancers. After ciclosporin use (average follow-up 6 years), 13 (46%) developed a total of 169 squamous-cell carcinomas. The interpretation is that the risk of squamous cell cancer of the skin is increased by ciclosporin in patients with psoriasis who have been exposed to PUVA.
Such risks should be balanced against the effectiveness of the drug and possible newer immunosuppressive agents.
Gupta AK, Chang P, Del Rosso JQ, et al (Sunnybrook Health Science Ctr, Toronto; St Michael’s Hosp, Toronto; Women’s College Hosp, Toronto; et al)
Onychomycosis in Children: Prevalence and Management
Pediatr Dermatol 15: 464-471, 1998
The adult rate of infection as the authors report is 6.9%. In children up to 18 years it is .16 to .44 per cent, and higher in Down’s syndrome. Laboratory confirmation is necessary.
Oral therapy with itraconazole fluconazole and terbinafine is effective. The authors suggest local application for mild to moderate infections only.
M. Naumann, N. J. Lowe, et al
Botulinum Toxin Type A in Treatment of Bilateral Primary Axillary Hyperhidrosis: Randomised, Parallel Group, Double Blind, Placebo Controlled Trial
BMJ No.7313, September 15, 2001, Pg. 596-9
Summary : This was a multicentre, randomised, parallel group, placebo controlled trial in patients aged 18-75 years with bilateral primary axillary hyperhidrosis sufficient to interfere with daily living, in 307 completed cases.
Patients received either botulinum toxin type A (Botox) 50 U per axilla or placebo by 10-15 intradermal injections evenly distributed within the hyperhidrotic area of each axilla, defined by Minor’s iodine starch test.
Percentage responders (patients with ³ 50% reduction from baseline of spontaneous axillary sweat production) at 4 weeks, patients’ global assessment of treatment satisfaction score, and adverse events were noted.
The results revealed that at 4 weeks, 94% of the botulinum toxin type A group had responded compared with 36% of the placebo group. By week 16, response rates were 82% and 21% respectively.
Results of all other measures of efficacy were significantly better in the botulinum toxin group than the placebo group. Significantly higher patient satisfaction was reported in the botulinum toxin type A group than the placebo group. Treatment related adverse events were reported by 27 patients in the botulinum toxin group and 4 in the placebo group.
Eleven patients in the botulinum toxin group perceived an increase in non-axillary sweating after treatment compared with none of the control group. All 11 were responders and increases were reported at various body sites.
Will the Sunscreens of the Future Contain Interleukin-12?
Lancet, Vol. 358, December 2001, Pg. 1878
German investigators have revealed that interleukin-12 (IL-12) has the ability to inhibit keratinocyte apoptosis induced ultraviolet-B (UVB) irradiation.
Instead of initiating programmed cell death, the cells are induced by IL-12 to repair their damaged DNA. This indicates that cytokines can reduce the impact of exposure to ultraviolet light, and therefore may be a valuable addition to suncreams.