欧洲皮肤和性病学会第9届会议 （2000-10）

 

欧洲皮肤和性病学会第9届会议

瑞士日内瓦

2000年10月11-15日

Conference Report
9th Congress of the European Academy of Dermatology and Venereology
Geneva, Switzerland
October 11-15, 2000

Abrar A. Qureshi, MD

---

Introduction

The Congress of the European Academy of Dermatology and Venereology (EADV) is an annual event hosted by a city in the European Union. Prominent speakers are invited from all over the world, including the United States, but most attendees are European dermatologists. This report highlights some of the interesting, clinically relevant information presented at the meeting but should not be considered an encyclopedic summary.

Photodermatology

Dr. Gillian Murphy,^[1] from Dublin, Ireland, discussed her approach to the diagnosis of photodermatoses in children. The age of the child, pattern of the rash, and diagnostic biopsy are important elements in making a diagnosis. Genetic photodermatoses may present at or around birth, and differential diagnosis includes Günther's disease (erythropoietic porphyria), erythropoietic protoporphyria, xeroderma pigmentosum, and Smith-Lemli-Opitz syndrome. Acquired photodermatoses in infants include neonatal lupus, acquired porphyrias, and drug-induced and solar urticaria.

Dr. Murphy highlighted important clinical pearls:

• If the patient complains of a burning sensation with no visible rash, consider a drug or chemical etiology. If linear scars are seen, erythropoietic protoporphyria must be ruled out.

• The time of onset of rash or other symptoms after light exposure can also aid in the diagnosis. For example, solar urticaria occurs almost immediately, but a sunburn occurs 24-48 hours after exposure.

• The differential for maculopapular rash includes polymorphous light eruption, actinic prurigo, lupus erythematosus (LE), and erythema multiforme (EM).

• The differential for blisters induced by light includes EM, hydroa vacciniforme, LE, and drug-induced blisters.

Dr. John Hawk,^[2] from London, United Kingdom, outlined recent advances in our understanding of chronic actinic dermatitis (CAD). Patients with CAD often present with an eczematous eruption that worsens in the summer and is sharply demarcated at sleeves or collars. The upper eyelids are spared, and pathology shows changes consistent with an eczematous process.

Dr. Hawk presented a new hypothesis that may help explain the pathophysiology of CAD. He reasoned that CAD is similar to an allergic contact dermatitis, except that the allergen is possibly photoactivated. Once triggered, an immune response is provoked. He also noted that if there is no resolution of the disease with treatment, a diagnosis of cutaneous T-cell lymphoma should be considered and repeat biopsies should be performed.

Androgenetic Alopecia in Men

Dr. David Whiting,^[3] from Dallas, Texas, presented clinical pearls for the treatment of androgenetic alopecia in men at a satellite symposium sponsored by Merck Sharp & Dohme. Early castration and absence of dihydrotestosterone in men has been shown to reduce the incidence of androgenetic alopecia, whereas there are no similar experiments in women. Although the onset of alopecia is about 50 years in men and 60 years in women, progression of hair loss is more rapid in women (within a decade), whereas in men, alopecia develops over many decades. It is interesting to note that as the anagen-telogen ratio is altered in androgenetic alopecia, the number of telogen hairs is consequently increased.

Parting the hair to examine hair loss in relation to a standardized scalp site is often more helpful than doing a cursory examination of the hair or scalp from a distance. When hair is parted, factors such as hair length, hair dyes, or hair conditioners that give hair more body seem to play a less prominent role in estimating progression of hair loss. Dr. Whiting prefers to part the hair on the vertex of the scalp and estimate hair loss while examining the scalp with hair parted centrally. For the estimation of midscalp hair loss in men, he also uses the Norwood-Hamilton scale. In women, he uses the Ludwig scale to clinically grade hair loss.

Primary laboratory tests in patients with androgenetic alopecia include a dehydroepiandrosterone sulfate, free testosterone, and androstenedione. Secondary laboratory tests to consider if the first panel is normal are luteinizing hormone, follicle stimulating hormone, and prolactin.

Dermatologic Applications of Botulinum Toxin Type A

Dr. Markus Naumann,^[4] from Wurzburg, Germany, provided data from his institution on the use of botulinum toxin type A (Botox) for palmar/plantar and axillary hyperhidrosis. Side effects of botulinum toxin A include pain during injection, hematoma formation (9% to 25% of patients), and weakness (0% to 25% of patients experience weakness in hand muscles). He outlined 3 important points to consider when using botulinum toxin A:

1. Dose: In Dr. Naumann's hyperhidrosis studies, high dose is definitely better than a lower dose. However, there is a plateau effect at about 4 mouse units (MU). The area of hypohidrosis induced by 4 MU is no greater than that induced by 7 MU. However, an injection of 4 MU was more efficacious than an injection of 1 MU, 2 MU, or 3 MU.

2. Delivery: Although the Dermo-jet has been used to deliver botulinum toxin A, a needle achieves much better effects.

3. Immune response: One of the pitfalls of using large quantities (> 200 MU) of botulinum toxin A during 1 session is that patients can potentially develop an antibody response to the 200 MU per session.

Dr. Naumann also brought up interesting points about long-term use of botulinum toxin A. He noted that when botulinum toxin A is used chronically to temporarily inactivate muscles, there is an element of atrophy of the muscles treated and hence a built-in benefit to long-term use in these patients. However when treating hyperhidrosis, even after multiple treatments, no sweat gland atrophy was seen and no change in sweat-generating capacity was noted.

Melanoma Update

Dr. Hubert Pehamberger,^[5] from Vienna, Austria, presented an update on his group's work in the use of antisense oligonucleotides in melanoma patients. Antisense oligonucleotides are chemically modified stretches of single-stranded DNA that are synthesized in a nonbiologic system, and are complementary to the corresponding RNA strands that are being targeted with this technology.

Malignant melanoma responds poorly to chemotherapy. What makes melanoma cells chemoresistant? Human melanoma cells have been shown to express Bcl-2 90% of the time. Because Bcl-2 protects cells from undergoing programmed cell death, or apoptosis, cells expressing Bcl-2 seem to be protected from the apoptotic effect of chemotherapeutic agents. Dr. Pehamberger's group has shown that after using antisense oligonucleotides to Bcl-2, melanoma responds more favorably to chemotherapy in SCID mice.^[6] He presented new data at this meeting that seem to corroborate these findings in human subjects with metastatic melanoma.^[7] Bcl-2 antisense oligonucleotides (augmerosen) in combination with dacarbazine was used in patients with advanced malignant melanoma expressing Bcl-2. In a within-patient dose escalation protocol, 14 patients with metastatic malignant melanoma were given augmerosen intravenously or subcutaneously (0.6 mg/kg to 6.5 mg/kg) plus dacarbazine. The regimen was well tolerated. Doses of 1.7 mg/kg and higher led to a 40% decrease in Bcl-2 protein in melanoma samples compared with baseline. Increased apoptosis in the tumor was noted with dacarbazine therapy, with estimated median survival exceeding 12 months.

Topical Cidofovir

Dr. Donato Calista,^[8] from Cesena, Italy, and Dr. Robert Snoeck, ^[9] from Leuven, Belgium, spoke at different sessions about new uses of topical cidofovir. Cidofovir is an acyclic nucleoside analog that has been used systemically as an antiviral agent against DNA viruses. It has been used intralesionally in patients with esophageal and laryngeal papillomatosis with good results.^[10-12]

A 1% topical cidofovir preparation also has been used on condyloma acuminata with good results. The cream remained stable and efficacious for 4 months. Further randomized controlled trials need to be designed to evaluate the efficacy of topical cidofovir in the treatment of human papilloma virus-related conditions. The major disadvantage of topical cidofovir will be the expense of therapy.

Basal Cell Carcinoma

Dr. Erwin Epstein,^[13] from San Francisco, California, discussed the work at his institution that has furthered our understanding of the pathophysiology of basal cell carcinoma (BCC). In a very elegant manner, he brought together years of work on the hedgehog family of genes, including Patched (Ptc) and Smoothened (Smo) genes, and demonstrated the association between Ptc gene mutations and the development of BCCs. The Ptc gene can be mutated if DNA damage occurs through ultraviolet light-mediated pathways or if there is an inherited mutation in 1 or both Ptc alleles.

It is interesting that mice completely deficient in Ptc form spontaneous BCCs without requiring light exposure. These Ptc -/- homozygotes are similar in phenotype to the basal cell nevus syndrome (BCNS). However, mice heterozygous for the Ptc gene +/- carry 1 normal allele for Ptc and hence do not develop spontaneous BCCs. These mice require ultraviolet radiation to manifest BCCs clinically.

The pathway for Sonic hedgehog (Shh) and the Ptc and Smo genes is one of negative feedback. Normally, Ptc has a suppressive effect on Smo (both are transmembrane proteins). If Ptc is mutated, there is no suppressive effect on Smo, thus allowing for BCC formation. Shh can also bind to Ptc and shut off Ptc's suppressive effect on Smo. Hence an overriding excess of Shh can bind all Ptc molecules and relieve suppression on Smo, thus allowing BCCs to develop. This process was also shown in a mouse model overexpressing Shh with normal Ptc genes that developed BCCs.

Evaluation of the Patient With a Blistering Disease

Marcel Jonkman,^[14] from Brussels, Belgium, summarized a practical clinical approach to the patient with a blistering disease. He outlined the following step-wise workup:

1. Take a medication history. Drug-induced blistering diseases are relatively common and frequently missed.

2. Evaluate mucous membranes in all patients, including nasal, oral/pharyngeal, urethral meatus in men, and vulva in women.

3. Take clinical photographs, if possible, to follow clinical improvement or progression.

4. Consider taking a punch biopsy for H&E from lesional skin, preferably from the border of the lesion. Be careful not to twist off the epidermis or scale.

5. Consider taking a punch biopsy from perilesional skin for immunofluorescence. Kept in the correct media, it can be stored or mailed over 24 hours.

6. Serum for indirect immunofluorescence can be helpful.

7. Communicate with the primary care physician. Also consider checking blood pressure (especially if the patient uses cyclosporine frequently) and performing antinuclear antibody and thyroid-stimulating hormone tests.

Dr. Jonkman made the following suggestions for managing patients on long-term steroid therapy:

1. Check blood pressure and heart rate at every visit.

2. Counsel patient on dietary habits.

3. Consider checking a chest x-ray to rule out tuberculosis, or check a Mantoux test.

4. Obtain a baseline electrocardiogram.

5. If the patient is from the tropics, check stool for ova and parasites.

6. Consider checking stool for occult blood, and ask about a history of diverticulitis, which can be masked when on steroids.

7. If patient is on more than 7.5 mg per day of prednisone, consider bone densitometry -- especially in postmenopausal women. The patient will need supplemental calcium at every age, the dose increasing with increased age.

Urticaria: Treatment Beyond Antihistamines

Dr. Clive Grattan,^[15] from Norwich, United Kingdom, discussed the treatment of urticaria, focusing primarily on treatment without antihistamines. He noted that most cases of chronic urticaria are idiopathic. Before a patient is labeled with a diagnosis of idiopathic urticaria, it is mandatory to rule out thyroid disease (antithyroid antibodies). The examiner should also consider a gastrointestinal evaluation to rule out Helicobacter pylori infection, check stool for ova and parasites, and consider checking serum protein electrophoresis. Dr. Grattan also recommended a skin biopsy to confirm the diagnosis of urticaria, paying special attention to the presence of vasculitis or vasculopathy and type of infiltrate (lymphocytic vs neutrophilic).

Nondrug approaches to the treatment of urticaria include avoiding nonsteroidal anti-inflammatory drugs (especially aspirin) and angiotensin-converting enzyme inhibitors, and reducing stress and alcohol intake.

The mainstay of nonhistamine drug therapy is systemic corticosteroid therapy, because few other nonhistamine drugs have any beneficial effects in patients with chronic urticaria. However, due to the side effects of long-term corticosteroid therapy, these drugs should be reserved for short-term therapy or very severe cases.

Dr. Grattan summarized the general approaches to various forms of urticaria. For angioedema, he recommended steroids and epinephrine. For pressure urticaria, he recommended steroids and sulfasalazine. For thyroid-related problems, he recommended thyroxine, and for aspirin-related urticaria, he recommended montelukast. For neutrophilic infiltrates seen on biopsy in an urticarial eruption, he recommended considering colchicine.

Evidence-Based Dermatology: Treatment of Herpes Virus Infections

A comprehensive review of published evidence on current therapeutic practices for herpes virus infections was presented by Dr. Vera Mahler,^[16] from Erlangen, Germany. When treating the immunocompetent patient with dermatomal varicella zoster virus infection (shingles), multiple antiviral agents are available. Controversies include:

• There is no significant difference in postherpetic neuralgia outcome among the various antiviral agents.

• Acute pain may be somewhat better controlled with famciclovir therapy.

• No data are available comparing intravenous acyclovir vs oral acyclovir therapy.

• Therapy with antiviral agents is beneficial if started within 72 hours after onset of rash.

• Systemic steroids help reduce acute pain but have no effects on postherpetic neuralgia.

When treating an adult with chicken pox, antiviral therapy has no impact on the rate of complications such as pneumonia. However, there is a 0.5-day reduction in the duration of fever, a 2-3 day reduction in the duration of rash, and a nearly 50% reduction in rash severity.

Dr. Mahler also addressed important issues pertaining to varicella zoster immune globulin (VZIG). Its use can be considered in household exposures, face-to-face contact of 5 minutes or more, or 1 hour of indoor contact with a patient with documented varicella. VZIG can be administered up to 10 days after exposure.

Computers in Dermatology

Dr. Ramon Grimalt,^[17] from Barcelona, Spain, presented a thorough overview of a number of products available to dermatologists who want to take digital photographs for record-keeping or presentations. He spent some time discussing the price and resolution of various digital cameras. The camera that seems to win in terms of reasonably good resolution and portability is the Nikon 950. This camera has been used by some dermatologists with a dermatoscope, and it can also capture images via the eyepiece of a microscope.

Dr. Grimalt also discussed the transfer of images from digital cameras to a computer via the use of memory cards or chips that are sold with each camera. For dermatologists interested in scanning Kodachromes, he discussed the option of purchasing a slide scanner. For storage and rapid retrieval of images, a number of software systems are available. Storage can be expensive, so it is imperative to use a file format that uses the least amount of memory on a hard disk yet preserves resolution. He discussed two commonly used formats that have been used to save such files. The graphic interchange format (GIF) is generally preferred for images made up of lines and solid blocks of color. The joint photographic expert group (JPEG) format is generally preferred for photographs and other images with continuous gradations of tone. Both formats are commonly used and seem to work well.

For presentations, Dr. Grimalt recommended the Powerpoint format, where digital images from any format can be loaded, edited, and presented with excellent resolution on a screen via an LCD projector.

Although investing in a digital system may be expensive at the outset, it will help save both time and money in the long term, Dr. Grimalt said.

Conclusion

The EADV Congress provides an outstanding opportunity for European dermatologists to present their work and interact with colleagues. The meeting also attracts dermatologists from the international arena due to the high quality of the presentations and the discussion of both basic science topics and clinical issues. It is encouraging to see how basic science research is becoming applicable in the outpatient dermatology clinic, from identification of the genetic defect in patients with basal cell nevus syndrome to identification of cidofovir as a new therapeutic modality for warts.

---

References

1. Murphy G. Photodermatoses in childhood: Photodermatology Day. Sponsored by European Society for Photodermatology. (Sister Societies Pre-Congress Meeting.) Program of the 9th Congress of the European Academy of Dermatology and Venereology; October 11-15, 2000; Geneva, Switzerland. Page 24.
2. Hawk J. Chronic actinic dermatitis: Photodermatology Day. Sponsored by European Society for Photodermatology. (Sister Societies Pre-Congress Meeting.) Program of the 9th Congress of the European Academy of Dermatology and Venereology; October 11-15, 2000; Geneva, Switzerland. Page 24.
3. Whiting D. Androgenetic alopecia: Androgenetic Alopecia in Men: New Options in a New Millennium. Sponsored by MSD. (Satellite Symposia) Program of the 9th Congress of the European Academy of Dermatology and Venereology; October 11-15, 2000; Geneva, Switzerland. Page 26.
4. Naumann M. Botulinum toxin type A in the treatment of hyperhidrosis: Dermatologic Applications of Botulinum Toxin Type A. (Satellite Symposium.) Program of the 9th Congress of the European Academy of Dermatology and Venereology; October 11-15, 2000; Geneva, Switzerland. Page 26.
5. H Pehamberger. Bcl-2 antisense therapy in melanoma: Skin Tumours Symposium. Program of the 9th Congress of the European Academy of Dermatology and Venereology; October 11-15, 2000; Geneva, Switzerland. Page 44.
6. Jansen B, Schlagbauer-Wadl H, Brown BD, et al. Bcl-2 antisense therapy chemosensitizes human melanoma in SCID mice. Nat Med. 1998;4:232-234.
7. Jansen B, Wacheck V, Heere-Ress E, et al. Chemosensitisation of malignant melanoma by BCL2 antisense therapy. Lancet. 2000;18:1728-1733.
8. Calista D. Topical cidofovir for the treatment of recalcitrant cutaneous infections in patients with AIDS. Program of the 9th Congress of the European Academy of Dermatology and Venereology; October 11-15, 2000; Geneva, Switzerland. Page 45.
9. Snoeck R, Andrei G, De Clereq F. Cidofovir: potential for the treatment of HPV associated lesion: Human Papillomavirus Infections. Program of the 9th Congress of the European Academy of Dermatology and Venereology; October 11-15, 2000; Geneva, Switzerland. Page 30.
10. Snoeck R, Wellens W, Desloovere C, et al. Treatment of severe laryngeal papillomatosis with intralesional injections of cidofovir. J Med Virol. 1998;54:219-225.
11. Wilson WR, Hashemiyoon R, Hawrych A. Intralesional cidofovir for recurrent laryngeal papillomas: preliminary report. Ear Nose Throat J. 2000;79:236-238, 240.
12. Pransky SM, Brewster DF, Magit AE, Kearns DB. Clinical update on 10 children treated with intralesional cidofovir injections for severe recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg. 2000;126:1239-1243.
13. Epstein E. Basal cell carcinoma: Plenary Lecture. Program of the 9th Congress of the European Academy of Dermatology and Venereology; October 11-15, 2000; Geneva, Switzerland. Page 30.
14. Jonkmann M. Pretreatment workup of patients with autoimmune blistering disorders: Bullous Disorders. Program of the 9th Congress of the European Academy of Dermatology and Venereology; October 11-15, 2000; Geneva, Switzerland. Page 44.
15. Grattan C. Treatment beyond antihistamines: Urticaria. Program of the 9th Congress of the European Academy of Dermatology and Venereology; October 11-15, 2000; Geneva, Switzerland. Page 30.
16. Mahler V. Treatment of herpes virus infections: Evidence Based Dermatology. Program of the 9th Congress of the European Academy of Dermatology and Venereology; October 11-15, 2000; Geneva, Switzerland. Page 55.
17. Grimalt R. A practical approach to digital photography. Computers, Internet, and Teledermatology. Program of the 9th Congress of the European Academy of Dermatology and Venereology; October 11-15, 2000; Geneva, Switzerland. Page 55.