Meeting report I I II II IIII

Noah Worcester Dermatological Society

Twenty-sixth Annual Meeting, Scottsdale, AZ, March 6-12, 1983

Silas Wallk, M.D., Esther Farney, M.D., William Gentry, M.D., and Loren E. Golitz, M.D. Chicago, IL, Pittsburgh, PA, Minneapolis, MN, and Aurora, CO

The twenty-sixth annual meeting of the Noah Worcester Dermatological Society was held at the Scottsdale Registry Resort on March 6-12, 1983, under the presidency of Jerral S. Seibert, M.D. The scientific program was chaired by Paul Van- dersteen, M.D.

Sigfrid A. Muller, M.D., presented his experi- ences in the treatment of alopecia totalis with di- nitrochlorobenzene (DNCB). Thirty-two patients with alopecia totalis between the ages of 17 and 62 years were treated in the preceding 3�89 years by the application of DNCB in acetone to the scalp after being successfully sensitized initially.

Approximately 50% of the patients regrew 90% of their scalp hair, whereas approximately 25% of the patients were grouped as partial responders, regrowing amounts less than this. About 25% of the patients were grouped as nonresponders, i.e., regrowing less than 10% of normal scalp hair.

The concentrations of DNCB varied from 0.00001% to 1.0% and were adjusted every 2 weeks if necessary in order to maintain a slight to mild scalp dermatitis. Significant hair regrowth usually began after 8 to 12 weeks of treatment and occasionally was rapid and diffuse, although more commonly progressive. The technic consisted of the application of the medication to the scalp every 3 days in the morning and shampooing at night. Severe forms of dermatitis of the scalp appeared to retard hair regrowth.

Relapses were common and often associated with the development of hyposensitization to the DNCB. There was no way of predicting respon-

Reprint requests to: Dr. SJ]as Wallk, 2434 West Peterson Ave., Chicago, IL 60659.

ders from nonresponders. Complications were not serious. There were no changes in the blood count, the chemistry group, or urinalysis during the treatment.

Other than steroids, DNCB is one of the most successful treatments of alopecia areata. The question of the permanence of satisfactory hair regrowth remains unanswered, but continuous or intermittent therapy is likely to be needed. Main- tenance of satisfactory hair regrowth was accom- plished by the application of the DNCB every 2 weeks.

Harry L. Roth, M.D., discussed Zyderm Colla- gen Implant. Severely scarred aene patients re- ferred and treated at the Stanford Plastic Surgery Department for 9 years plus 300 other patients had been followed over the preceding 3 years.

Zyderm Collagen Implant is a sterile, highly purified bovine dermal collagen dispersed in a phosphate-buffered physiologic saline containing 0.3 % lidocaine. The resultant suspension becomes a highly viscous material that is kept frozen until ready for use and then brought to room tempera- ture. When Zyderm Collagen Implant is intrader- mally injected, the implant is invaded by the host's fibroblasts, which gives the implant the same characteristics as native collagen. Once in place, the implant condenses, usually in the range of 60% to 75%. Two or more implant sessions at intervals of at least 2 weeks are required to achieve the desired effect. Therefore, the contour defi- ciency may be overcorrected to 2.5 to 2.0 times the depth ofthe lesion.

Zyderm Collagen Implant is indicated in the correction of contour deformities of the dermis in nonweight-bearing areas. The etiology and dis-

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tensibility of the lesion, tissue stress of the implant site, and the tissue site where the implant is placed will affect the degree of contour restoration and the duration of the correction. Severely indurated, sharply marginated, and very superficial lesions (e.g., ice pick acne scars, viral pockmarks, and superficial wrinkles such as some perioral lines) have proved difficult to distend and therefore to correct. Caution should be used in implanting into the periorbital area or the vermilion border of the lip as these areas are susceptible to prolonged overcorrection. Following implant stabilization, the long-term persistence of the contour correction is variable due to the stresses of aging at corrected sites. Zyderm Collagen Implants are no substitute for a face-lift.

Kent M. Hardy, M.D. , reported on tattoo re- mova l -mark ing and unmarking skin. Tattooing began in ancient Egypt and has been in and out of vogue in many societies worldwide. Tattoos have been removed successfully by dermabrasion, salabrasion, planing, and excision with primary closure or grafting. These methods are time- consuming and often expensive. Unsightly scar- fing is common.

The carbon dioxide laser has been available for ablation of tattoos and treatment of other skin ab- normalities since 1972. The radiation is so sharply localized that coagulation necrosis is limited to a very narrow area at the crater edge. The new lasers are freed from the microscope and the beam can still be directed accurately. The COs laser is con- trolled by varying length of exposure, power (watts), and focus and is more rapid than the argon laser.

The CO2 laser was used to treat 520 patients in an office setting with an average of eight patients treated daily. Warts were treated on 154 patients, mainly on finger pads or palmar areas. Plantar verrucae refractory to other treatment modalities were also treated with the CO2 laser. After the area was anesthetized, the lesions were charred with a continuous defocused beam at 8 to 10 watts. The char was removed with a No. 10 scalpel blade, and the base of the lesion was removed with the beam in focus. Postoperative bleeding occurred in two patients, and pain requiring medication, in four patients. No scarring was seen on follow-up.

Three patients had recurrence of their lesions. Seventy-five patients with facial milia responded well to the focused laser beam at 4 watts with 0.05-second exposure. No anesthesia was neces- sary. The site heals in 3 to 5 days.

Decorative tattoos were removed by using the highly defocused beam at 10 to 20 watts to blister off the epidermis. Three successive passes with the beam almost in focus were required to remove 50% to 75% of the tattoo pigment. Three per- cent hydrogen peroxide was used to remove the char between laser applications. Residual pigment sloughed off in the healing process. Wounds fo~- lowing tattoo removal required 2 to 4 weeks to reepithelialize. The treated area remained very erythematous for 2 to 4 months.

Peter J. Lynch, M.D., as a special guest for the Harold O. Perry Lecture, presented "Neutrophilic Dermatoses and Myeloproliferative Malignancy." The similarities between bullous hemorrhagic pyo- derma gangrenosum and Sweet's syndrome were reviewed. In 1972 Perry and Winkelmann de- scribed three cases of an unusual neutrophilic der- matosis occurring in association with leukemia. The cutaneous lesions were characterized by the presence of hemorrhagic bullae and a superficial necrotizing ulcer. Since then, a total of fifteen cases have been reported in the English language litera- ture.

Of the myeloproliferative disorders, which in- clude polycythemia vera, preleukemia, and par- oxysmal hemoglobinuria, the acute and chronic myelocytic leukemias are associated with bullous hemorrhagic pyoderma gangrenosum. Eight men and six women were reported in this series, with age ranging from 28 to 70 years. Unlike pyoderma gangrenosum, these lesions are localized to the legs but are common on the face, chest, and distal aspects of the arms, often at sites of trauma, i.e., needle punctures. Most patients had one or two lesions but three had numerous ulcers.

After ulcerative colitis, the most common dis- order is multiple myeloma. Laboratory findings include: increased complement, often decreased immunoglobulins, and disturbances in cell-medi- ated responsiveness. No immune complexes have been found. Histologically, there appears to be a polymorphonuclear response with no vasculitis.

Volume 11 Number 6 December, 1984

Noah Worcester Dermatological Society 1177

Nine of fourteen bullous pyodermas were leuke- mia-associated, and four of fourteen had leuke- mia first. Bullous hemorrhagic pyoderma gan- grenosum may precede leukemia.

The treatment consists of prednisone, 60 to 120 rag/day. Sulfa drugs (Dapsone) have been used in some cases. There is a good response, but relapse occurs with tapering of steroids. The prognosis is bad in that eleven of fourteen patients died.

Acute febrile neutrophilic dermatosis, or Sweet 's syndrome, was described in 1964 by Sweet. It may be considered as harbinger of bullous pyoderma gangrenosum and is charac- terized by fever, which may precede skin lesions, arthralgia, and malaise. The incidence appears to be higher in women and occurs between the ages of 30 and 65 years. Clinically, the lesions are red to dusky, edematous, vesicle-like papules and nodules and form large plaques with gyrate bor- ders. They appear mainly above the belt line and enlarge over days or weeks, affecting the face, neck, and extremities, often with episcleritis and conjunctivitis.

Laboratory findings include a leukocytosis in the range of 10,000 to 20,000 white blood cells. The biopsy specimen resembles that of pyoderma gangrenosum, with edema in the superficial der- mis and polymorphonuclear leukocytes in the deep dermis. The differential diagnosis includes erythema nodosum and erythema multiforme, but the great number of polymorphonuclear leuko- cytes are diagnostic.

The course is one of improvement in weeks, but there is a tendency to recurrence. There is no re- sponse to antibiotics, but there is a dramatic effect with prednisone, 30 to 60 mg/day tapered over weeks. If tapering is too fast, there is recurrence.

Associated diseases include ulcerative colitis, paraproteinemia, solid tumors, and myeloprolif- erative disorders. Both bullous hemorrhagic pyo- derma gangrenosum and Sweet's syndrome share in common the presence of fever, a dense in- flammatory infiltrate of neutrophils, an absence of vasculitis, and an absence of infectious organisms. Patients experience considerable morbidity in spite of the steroid-responsive nature of the conditions. Mortality from the associated myeloproliferative disease is high. These observations suggest that

bullous pyoderma gangrenosum and Sweet's syn- drome are closely related and that both syndromes are likely to occur in a setting of serious my- eloproliferative disease.

Peter J. Lynch, M.D., discussed necrotizing fasciitis and related syndromes. This group of dis- eases occurs as the result of bacterial infection in the subcutaneous tissues. The severity of the in- fection is usually of considerable magnitude by the time the cutaneous changes are apparent. Early recognition and prompt intervention are of impor- tance. The first cutaneous changes are similar to those seen in ordinary cellulitis: redness, pain, and swelling. However, in these necrotizing infections notable edema extends well outside of the area of inflammation and the red color quickly assumes dusky violaceous hues. The central area of the color change often becomes anesthetic. Infections inadequately treated at this point are followed by the appearance of vesicles and bullae containing yellow or blood-tinged fuid. Gangrene and ulcer- ation may eventually develop.

Diagnostic procedures include palpation for crepitus, soft tissue radiograms for gas, and prompt incision in a search for pus. The most common predisposing circumstances include trau- ma (often a surgical procedure), diabetes, al- coholism, and other causes of immunosuppres- sion and debilitation. Cultures taken from the deep tissue usually reveal Streptococcus sp, Staphylococcus aureus, or gram-negative or- ganisms. Mixed infections, especially with anaerobic bacteria, are increasingly recognized. Treatment requires prompt surgical debridement as well as broad-spectrum intravenous antibiotics.

E. Edgar Allen, M.D., discussed streptococcal gangrene. In 1924, Frank L. Meleney, M.D., re- ported twenty cases of a gangrenous condition from which streptococcal organisms were cul- tured that he called "hemolytic streptococcal gangrene." Two cases of streptococcal gangrene affecting the lower extremities were presented, along with a review of 102 cases from the litera- ture. Both of these patients required above-knee amputation but did survive. The reported mortality of this condition in the preantibiotic era was 16%. Despite availability of antibiotics, the mortality of sixty-six more recent cases was 18%.

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All age groups have been affected; males pre- dominate. Most have previously been healthy and free of immunologic defects. Lesions are swollen and red with indistinct borders that initially are painful but often later become painless. Redness may turn to dusky blue. Fever, rapid spread, and lethargy are common, but lymphangitis and lym- phadenopathy are unusual. The most important treatment is vigorous early surgical debridement.

The third Alfred L. Weiner Lecture, entitled "The Basement Membrane Zone-A High-Power View," was presented by Stephen I. Katz, M.D., Ph.D., chief of the dermatology branch of the Na- tional Cancer Institute. The epidermal basement membrane zone is approximately 1 /x thick and is composed of four ultrastructurally distinct areas. These are the basal cell plasma membrane, the lamina lucida, an electron-lucid area, the lamina densa, an electron-dense area, and the subbasal zone containing anchoring fibrils. Immunofluo- rescent studies show deposits of immunoreactants in the epidermal basement membrane zone in dis- eases such as herpes gestationis, bullous pem- phigoid, cicatricial pemphigoid, dermatitis her- petiformis, and the linear IgA dermatoses. Two constituents of the basement membrane zone in- clude laminin and bullous pemphigoid antigen. Studies utilizing the Engelbreth-Holmes-Swarm (EHS) tumor of mice, a tumor that resembles a cylindroma and produces large amounts of base- ment membrane zone material, have demonstrated both laminin and type IV collagen in the basement membrane zone.

Type IV collagen tends to be located in the region of the lamina densa, while laminin is found in the region of the lamina lucida. Laminin is dif-

ferent from bullous pemphigoid antigen, which tends to adhere to the basal cell plasma membrane. Bullous pemphigoid antigen weighs 220 daltons, is synthesized by epidermal cells, and is distinct from filamentous material and laminin. Using antibodies directed against the various immuno- reactants of the basement membrane zone, it is possible to identify the location of blister forma- tion in various dermatoses. As an example, Dr. Katz cited the studies with epidermolysis bullosa using KF-1 monoclonal antibody, which distin- guishes between the dominant and recessive forms of epidermolysis bullosa, based upon the anatomic location of the blister. Utilizing new information about the basement zone helps to establish more precisely a correct diagnosis and to understand better the pathophysiologic mechanisms operating in diseased skin.

James S. Taylor, M.D., discussed environmen- tal acne, a continuing problem. Occupational acne is a variety of ache venenata resulting from contact with petroleum and its derivatives, coal tar prod- ucts, or certain halogenated aromatic hydro- carbons. The latter includes polyhalogenated naphthalenes, biphenyls, dibenzofurans, dibenzo- p-dioxins, and certain chlorinated benzene com- pounds. The eruption may be mild, involving lo- calized, exposed, or covered areas of the body. In the case of chloracne it is often severe and more widespread, involving almost every follicular orifice. Chloracne represents one of the most sen- sitive biologic indicators of toxicity to certain chemicals and serves as a marker of the medical and environmental impact of contamination of technical grade chemicals with potentially highly toxic intermediates.