Pacific Dermatologic Association

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Pacific Dermatologic Association Thirtieth Annual Meeting, Coronado, CA, Sept. 18-21, 1978 Harry L. Arnold, Jr., M.D., and Rees B. Rees, M.D. Honolulu, HI, and San Francisco, CA

The Pacific Dermatologic Association (PDA) followed its traditional pattern of returning every 10 years to the scene of the inaugural meeting in 1948, the landmark Hotel Del Coronado, Coronado, CA. CLINICOPATHOLOGIC CONFERENCE For four mornings, Robert Go[tz, M.D., with the able assistance of William Wood, M.D., from Vancouver, conducted the one-hour clinicopathologic conference. The twin-screen format, traditional since Paul Fasal introduced it in 1956, was used. Lauren Ackerman, in 1948, originated the term "verrucous carcinoma" to describe warty, often extensive tumors of the mouth that had a welldifferentiated but invasive histologic picture. Subsequently, these tumors have been described in the larynx and esophagus, and synonyms have included "oral florid" (i.e., florid oral!) papillomatosis, florid papillomatosis of the larynx, and giant condyloma of Buschke and Loewenstein. The term "papillomatosis curls carcinoides" has been used to describe a variety of lesions thought to be pseudocarcinomatous in nature. In 1954, British authors used the term "epithelioma cuniculatum," three examples of which arose on the sole. A case represented as giant keratoacanthoma was considered by Goltz to be a proliferating pilar tumor of Wilson Jones (Wilson Jones E: Proliferating epidermoid cyst. Arch Dermatol 94:11, 1966). A case presented as spindle cell squamous carcinoma was thought to be such by Goltz. He agreed with Feldman and Barr in urging electron microscopy (EM) for problem cases such as this, which by light microscopy may be diagnosed as either atypical fibroxanthoma or spindle cell squamous carcinoma (Feldman PF, Barr RJ: Ultrastructure of spindle cell squamous carcinoma. Cutan Pathol 3:17, 1976). In differential diagnosis, one must con0190-9622/79/010083+ 12501.20/0 9 1979 Am Acad Dermatol

sider a fibrocytic lesion such as dermatofibrosarcoma protuberans (Battifora H: Spindle-cell carcinoma, ultrastructural evidence of squamous origin and collagen production by the tumor cells. Cancer 37:2275, 1976). EM findings pointed to possible mesenchymal metaplasia of squamous cells with the thought that collagen might actually be produced by these metaplastic cells. James Graham mentioned the routine use of EM on paraffin sections. Winkelmann felt this particular tumor might have been a fibroxanthoma. In a case presented as sebaceous nevus with basal cell carcinoma, Goltz referredto tumors related to the pilo-sebaceous-apocrine triad. Mehregan and Pinkus (Mehregan AH, Pinkus H: Life history of organoid nevi. Arch Dermatol 91:574, 1965) reported basal cell epithelioma as the commonest neoplasm in organoid nevi, but they also found syringocystadenoma papilliferum, solid hidradenomas, infundibulomas, sebaceous epitheliomas, apocrine cystadenomas, and keratoacanthomas. In discussing a cutaneous mixed tumor, Goltz stated that it is generally agreed that the epithelial cells of mixed tumors induce the mucoid changes in the stroma. Lever suggested the name "mucinous hidradenoma" for that reason. Chondroid syringoma was the title chosen-by Hirsch and Helwig (Hirsch P, Helwig EB: Chondroid syringoma. Arch Dermatol 84:835, 1961). Goltz became accustomed to using that term in his own laboratory. A ceruminoma strongly suggested cylindroma to Dr. William Wood. The term "ceruminoma" is used for both benign and malignant tumors of the ear canal. Most cases resemble hidradenoma of sweat gland origin, without the cylindromatous pattern seen in the presented case. Thus, Goltz accepted this case as a cylindroma rather than a ceruminoma in the usual sense. A malignant ceruminoma is formidable; a cylindroma is not. 83

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In discussing a case of multiple eccrine spiradenoma, Goltz stressed the presence of a rosetting pattern (Hashimoto K, et al: Eccrine spiradenoma: Histochemical and electron microscope studies. J Invest Dermatol 46:347, 1966). A cystic eccrine spiradenoma, a nodule on the forehead possibly related to trauma, was accepted as such by Goltz. He feels this is a new entity. A huge solitary lesion on the frontal scalp of a 35-year-old woman, Dr. William Wood felt, was probably a neurofibroma, of some interest because it was a large, solitary lesion. In fifty high-power fields, Dr. Wood counted two mitotic figures. He pointed out that even this small number of mitoses is worrisome in neurogenic tumors. In this case, both dermatofibrosarcoma protuberans and neurofibrosarcoma have to be considered. The numerous mast cells, confirmed with toluidine blue stain, gave further support for the neurogenic origin of the tumor. A suitable reference is by F. M. Enzinger: The A F I P Fascicle on Tumors of the Nervous System. A 3x5-cm cerebriform lesion, covered with small nodular elevations, in a 15-year-old boy, was a hairless nevoid growth clinically. In 1965, Gottlieb et al showed that the fine structure of nevus cells is comparable to that of epidermal melanocytes, in that they too contain melanosomes and pseudopodic cytoplasmic processes (Gottlieb B, Brown A L Jr, Winkelmann RK: Fine structure of the nevus cell. Arch Dermatol 92:81, 1965). Of a case presented as a cellular blue nevus superimposed on a mongolian spot, Goltz said he was not aware of reports of the origin of blue nevi from mongolian spots, and he wondered whether this was a coincidence. Might the "mongolian spot" be a deep extension of the nevoid process? (Leopold JG, Richards DB: The interrelationship of blue and common naevi. J Pathol Bacteriol 95:37, 1968.) In discussing a case of dermatofibrosarcoma protuberans, Goltz stressed the so-called "shelving" effect, i.e., the tumor extending out considerably beyond the area of epidermal infringement. This finding should help to differentiate this lesion from a large histiocytoma. Kempson, at Stanford, recently suggested dropping the term "dermatofibrosarcoma protuberans" and using instead the designation "storiform (whorled) fibrous histiocytoma." This term would help to differentiate the lesions from truly invasive and metastasizing sarcomas on the one hand, and from benign fibrous histiocytomas on the other. Storiform

Journal of the American Academy of Dermatology

fibrous histiocytomas (dermatofibrosarcoma protuberans) are usually recurrent and locally aggressive but seldom metastasize. In discussing a giant cell tumor of tendon sheath, Dr. William Wood mentioned that he sees one or two each week in a surgical pathology laboratory. The lesions consist of lipophilic synovial ceils and fresh hemorrhage plus hemosiderin deposition-and, of course, these arise from the tendon sheath and are benign but recurrent. Another term is "pigmented nodular tendosynovitis." This particular case had been reported (King DT, Millman AJ, Gurevitch AW, Hirose FM: Giant cell tumor of tendon sheath involving skin. Arch Dermatol 114:944, 1978). A malignant giant cell tumor of soft parts showed numerous large, multinucleated giant cells, often associated with histiocytic cells. There is evidence of phagocytosis. The present designation is "malignant fibrous histiocytoma" (Weiss SW, Enzinger FM: Malignant fibrous histiocytoma. An analysis of 200 cases. Cancer 41:2250, 1978). Malignant giant cell tumors of soft parts were defined by Guccion and Enzinger in 1972. (Guccion JC, Enzinger FM: Malignant giant cell tumor of soft parts. Cancer 29:1518, 1972). They divided the tumors into superficial and deep. The superficial ones are usually small, tending to occur on the leg, and frequently recur after excision, but only a small number metastasize, with fatal outcome. Deeper tumors are larger and involve skeletal muscle, deep fascia, and tendons. They occur chiefly on the thigh, and many patients develop pulmonary or wider metastases. It would appear that the present case may be one of the deeper variety of lesions. Of a subcutaneous papillary ependymoma in a 10-year-old boy, Goltz said that this tumor probably arises in the ilium terminale and extends through the sacrum to involve the subcutaneous tissue. Ependymoma is one of the commoner central nervous system tumors in children. Cilia and btepharoplasts may be diagnostic, particularly under the electron microscope. A 16-year-old white boy had a 2-year history of eosinophilic granuloma of the right side of the mandible. H e also had diabetes insipidus, together with skin lesions of the scalp, ears, forehead, axillae, and groin. There was a seborrheic dermatitis-like involvement of the scalp and forehead, with purpura. Histiocytosis X is now being classified into differentiated, intermediate, and undifferentiated forms. This case was differentiated

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because of apparent maturity of the nuclei, lack of prominent nucleoli, and hyperchromatism, all adding up, hopefully, to a better prognosis than in the other two forms. In discussing benign cutaneous lymphoplasia (a case of 3 years' duration), Goltz cited Caro and Helwig's review (Caro WA, Helwig EB: Cutaneous lymphoid hyperplasia. Cancer 24:487, 1969). They identified three groups of lesions: 1. L y m p h o c y t o m a cutis, frequently found in women, characterized by lymphoid follicles in the dermis. 2. Lymphocytic infiltration of the skin of Jessner and Kanof, which usually occurs in men. The infiltrate is composed almost entirely of lymphocytes with few histiocytes. Although usually patchy, it is periadnexal and perivascular and does not form lymphoid follicles. 3. Insect (properly, arthropod) bite granulomas. Histologically, these differ from the previous two groups by showing marked epidermal changes, a polymorphous infiltrate including many eosinophils and plasma cells, and frequently striking vascular changes. Goltz felt this case might be an example of primary plasmacytoma of the skin, a rare entity. The nosologic relationships of lymphomatoid papu!osis remain uncertain. Many authorities, including Macaulay himself, believe it is benign, and Valentino and Helwig concluded that it is only a variant of acute varioliform parapsoriasis with atypical lymphoreticular cells. On the other hand, in some cases originally diagnosed as lymphomatoid papulosis, lymphoreticular malignancy has developed. Verallo and Fand found that the atypical ceils in lymphomatoid papulosis contain more deoxyribonucleic acid (DNA) than normal, and it was suggested that they are probably tetraploid or octaploid cells. In the presented case, methotrexate was temporarily helpful. A case of Kimura's disease (angiolymphoid hyperplasia with eosinophilia) was presented. This condition occurs chiefly in young adults, and lesions are limited to the head and neck. Wilson Jones's disease occurs in older men. Winkelmann pointed out that the tumor is vascular, but the endothelial cells take on histiocytoid characteristics. In the discussion of a case of Wegener's granulomatosis with involvement of the lungs, respiratory tract, skin, etc., Goltz mentioned that 40% to 50% have skin involvement, including purpura, vesiculation, and ulceration. Only nineteen of Winkelmann's forty-three cases were diagnostic (ne-

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crotizing vasculitis) on biopsy. Therefore, one has to put together the clinical plus the histologic findings to make the diagnosis. The skin biopsy is seldom diagnostic by itself. Dr. Seiji of Tokyo presented a case of disseminated eosinophilic collagen disease of the acute type in a 21-year-old Japanese girl who developed an acute bullous disease and died within two weeks. There was a positive antinuclear factor, and IgE was 6,150 (normal, 1,000) IU, which Goltz did not know how to fit into the clinical picture. Serum enzymes were high. There were 14,200 WBC, with 77% eosinophils. William Wood reviewed the hypereosinophilic syndrome of Kazmierowski (Kazmierowski JA, Chusid MJ, Parrillo JE, et al: Dermatologic manifestations of the hypereosinophilic syndrome, Arch Dermatol 114:531, 1978). Individuals with this syndrome have involvement of the liver, spleen, and cardiovascular-respiratory tract. One half of them have skin lesions. Winkelmann commented that they have Churg-Strauss type lesions. Even eosinophilic myositis may occur. In a case of angioimmunoblastic lymphadenopathy with dysgammaglobulinemia and skin nodules, Goltz mentioned t h a t the proliferation of small vessels, formed only in lymph nodes, is more important than the changes in the skin. This is a polyclonal disease, with B cell immunoblasts present. Antinuclear factor was strongly positive but the lupus erythematosus preparation was negative. In this disease the process is thought to be triggered by a hypersensitivity reaction, in many cases to drugs such as the penicillins, sulfonamides, griseofulvin, analeptic drugs, or aspirin. Characteristic findings are intercellular deposits of amorphous, sludgy, eosinophilic material which is periodic acid-Schiff (PAS)-positive and stains partially like fibrin. EM shows this to be cellular debris, probably indicating extensive cell death. Amyloid is not found. The evolution of a nonneoplastic cellular proliferation into a true sarcoma may be in keeping with the "two-hit" hypothesis of Solomon and Saligman, in which there is thought to be a triggering of a preneoplastic proliferation by an antigenic stimulus, with later malignant transformation by an oncogenic event. This is like a graft-vs-host reaction. "Smaller-cleaved-cell lymphoma" of the scalp was considered to be a tenable diagnosis, but Goltz emphasized that it is often not possible to distinguish clearly in biopsy specimens of the skin between the large cell type, the small cell type, etc.

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It is really not the role of the dermatopathologist to make such distinctions on the basis of skin biopsy specimens. What is important is to make the diagnosis o f malignant lymphocytic tumor. Rappaport emphasized that what used to be called lymphosarcoma is now sometimes called malignant histiocytic tumor. The smaller cleaved-cell tumor is supposed to be made up of partially differentiated B cells, and it might be possible to identify them as B cells by identification of immunoglobulin by immunofluorescence. A case of pagetoid reticulosis (Woringer-Kolopp disease) was very much like the one published by Lever in 1977, consisting of a circumscribed verrucous plaque on the foot. Two forms of a disorder characterized by pagetoid infiltration of the hyperplastic epidermis by mononuclear cells appear to be emerging. One is a localized form with a relatively benign prognosis, and the other is a diffuse form; both may be simply a variant of mycosis fungoides, as suggested by Andreev. The original case of Woringer and Kolopp was a single infiltrated plaque on the wrist of a 13-year-old boy (Woringer F, Kolopp P: L~sion 6ryth~matosquameuse polycyclique de l'avant-bras 6voluant depuis 6 ans chez un gar~onnet de 13 ans. Ann Dermatol Syphiligr 10:945, 1939).The localized form seems to respond well to radiation therapy. In a case of oral nondystrophic bullous eruption of the ging~va (a variant of mucous membrane pemphigoid), Goltz mentioned that azathioprine (Imuran), 15 mg daily or every other day, might be effective. This case seems to fit the description of the entity described b y Forman and Nally (Forman L, Nally FF: Oral nondystrophic bullous eruption mainly limited to the gingivae. Br J Dermatol 96:111, 1977). Though nonscarring, it is in other respects mucous membrane pemphigoid. A case in a 60-year-old white man of balanitis plasmocellulare (Zoon's erythroplasia), presenting as a minimally symptomatic, smooth, erythematous, noninfiltrated macule on the distal dorsal shaft of the penis, of about 6 months' duration, was cured b y 0.05% desonide cream applied twice daily. James Graham in the discussion stated flatly that this lesion is a fixed drug eruption from tetracycline, maintained by continuous ingestion of the antibiotic. Nodular cutaneous amyloidosis in the nasolabial fold was unequivocally confirmed by Congo red stains. There were large numbers of plasma cells also. A Congo red stain shows red-green dichroism with polarization. Nodular cutaneous amyloidosis

Journal of the American Academy of Dermatology

is a separate form from other types of amyloidosis (Chapel TA, Birmingham DJ, Malinowski YE: Nodular cutaneous amyloidosis. Arch Dermatol 113:1248, 1977). A fascinating example of an unusual infection was that of cutaneous protothecosis, caused by an unusual organism in a patient with autoimmune disease (Felty's syndrome plus rheumatoid arthritis) on steroid and immunosuppressive therapy for 18 years. In ten reported cases, all adults, five of the nine infections were manifested clinically as olecranon bursitis. Water may have been the source of infection in four of these cases. Prototheca species are either achlorophyllous fungi or achlorophyllous green algae of the genus Chlorella. The organisms produce sporangia with endospores. Recommended treatment is 50 mg minocycline twice daily. Mycetoma due to Actinomadura madurae showed epidermal necrosis histologically, with underlying abscess formation and large, deeply basophilic sulfur granules composed of organisms with a radial arrangement of the small hyphae at the periphery. The designation of this organism as Actinomadura madurae was unfamiliar to Gottz. In the United States, Allescheria boydii is said to be the most common cause of mycetoma. According to Dr. Fred Roberts, the genus Actinomadura was created to cover a number of organisms previously classified as Nocardia, Actinomyces, or Streptomyces. The species isolated in this case has also been called Streptomyces madurae, Streptothrix madurae, and several other names. These are basically proteolytic soil organisms. Bone invasion is common but did not occur in this case. Septra (trimethoprim sulfamethoxazole) produced some improvement. This is a bacterial organism, gram-positive but not acid-fast. Dapsone might be worth .trying. Another example of the bizarre infections which occur in patients who are immunosuppressed for long periods of time is disseminated cutaneous mycobacterial infection. The organism in the presented case was Mycobacteriumfortuitum, a type IV mycobacterium. Some cases of Mycobacterium kansasii infection have previously been reported. The discussion of a case of perforating pseudoxanthoma elasticum (PXE) brought out the fact that elastosis perforans serpiginosa is not, as was previously thought, related to pseudoxanthoma elasticum. Rather, it was confused with the perforating form of PXE. This entity was reported by Graham and Hunter and also by Lund and

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Gilberg, as well as by Carpenter in a paper read at the American Dermatological Association meeting in 1978. The final case was that of giant congenital nevus with neurofibroma. In 1971, Thorne et al demonstrated that on EM examination, even nevus cells deep in the dermis that have a neuroid appearance on light microscopy contain melanosomes with dopa oxidase activity. These authors concluded that at least by EM, a clear-cut separation between nevus cells and Schwann cells is possible. PRESIDENTIAL ADDRESS

Jack McCleary, M.D., president of the PDA, spoke on the dermatologist's future. There will be an explosion in the number of MDs, and possibly a limitation of direct primary access to the dermatologist. The Federal Trade Commission is embarked on a course which may well abolish, or severely limit the influence of, the specialty boards. By 1990, there will be a 60% increase in the number of MDs, and in all there will be some 600,000 health care providers. In San Francisco at the present time, there are 525 MDs per 100,000 population. Dr. McCleary did not mention, however, that San Francisco is a referral center. Each new MD adds $250,000 to the total national annual expenditure for medical care. One out of every 172 persons in San Francisco is a lawyer; one out of every 190, a physician. Regarding primary health care systems, Senate Bill $52879, introduced by Jacob Javits, contains some of the recommendations of the Institute of Medicine in 1978, such as reimbursement of all MDs equally for the same procedure. It would also require patients in group practice to be assigned to a primary care physician who would have to refer them to the specialists--a costly bit of wheel spinning! Fifty percent of all trainees are now supposed to be in the primary care field. In 1914, the Federal Trade Commission dealt with unfair competition, but the scope of its activities was greatly broadened in 1975. Dr. McCleary concluded by saying he was a modern optimist, "one who believes that the future is uncertain." ADMINISTRATION

At the business meeting it was mentioned that the PDA now has 1,041 members. Those members reaching the age of 70 will no longer have to pay dues. The huge growth in the organization is presenting many problems, and various means of dealing with them are under consideration.

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SCLERODERlVIA Gustav Asboe-Hansen, M.D., o f Copenhagen spoke on " N e w Concepts on the Control of Scleroderma." The list of so-called "collagen" diseases is very long indeed. The pathology in scleroderma includes fibrosis, calcinosis, arteritis, myocardial edema (due to mucin), widening of the periodontal membrane, cataract formation, and many other changes. The disease affects mast cells, fibroblasts, macrophages, smooth muscle, ground substance, collagen, and elastica. Old elastica in scleroderma shows granular fibers, with mucopolysaccharide matrix between them. There is a vasoconstrictive response, and, as is well known, persistent edema leads to fibrosis. In collagen biosynthesis, there is assembly by the ribosomes of proline- and lysine-rich polypeptide precursors called "protocollagen." The proline and lysine are in turn hydroxylated to hydroxyproline and hydroxylysine. There is a decrease of hydroxyproline, proline, and hydroxylysine in scleroderma collagen. A partial list of drugs under trial in the treatment of scleroderma in Dr. Asboe-Hansen's institution includes hydralazine, chlorpromazine, diphenylhydantoin, dimethyl cysteine, penicillamine, glutamine, and levodopa. Penicillamine was the drug principally used, but unfortunately only six of ninety-three patients had a clear-cut response, even to a total of 1,075 gm in at least three years. Treatment should be started as early as possible. All of the drugs named are collagen inhibitors. There is a long list of side effects with penicillamine, and the trick is to use a low dose for a long period of time. Winkelmann says sodium diphenylhydantoinate is ineffective in children.

NAIL PROBLEMS Robert Baran, M.D., of Cannes, France, spoke on nail problems. He classified nail fragility into three categories: soft nails, brittle nails (in which there may be single or multiple longitudinal splits or onychoschizia), and friability. Nails are 15% water, but thorough hydration raises this to about 30%. Desiccati~r~, of course, leads to splitting of the nails. In dyskeratosis congenita there may be a central mechanism in the hypothalamus. Peripheral nerve damage may result in nail changes, as may oxidants and thioglycolates. Similar nail changes may result from iron lack. Calcium does not play a role. In syringomyelia there may be atrophic nail changes.

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Baran spoke of the syndrome of Bazex and Duprr, paraneoplastic acrokeratosis, in which all nails, as well as the ears and the nose, may be altered by hyperkeratosis and flaking caused by advanced internal malignancy. One may see some subungual hyperkeratosis in psoriasis. Onychoatrophy may occur. Dr. Baran showed nail changes strongly suggesting those of severe psoriasis, and Dr. Winkelmann, as an aside, said that these respond well to triamcinolone acetonide suspension intramuscularly, a suggestion in which we strongly concur. The "yellow nail" syndrome includes onycholysis, curvature in the longitudinal direction, and chronic paronychia of all nails---the yellow-graygreen color of the toenails may be particularly striking. Nails may shed. Vitamin E, as recommended by Samuel Ayres, Jr., may be effective. Pterygium inversus unguium, described in California, may be accompanied by paroxysmal pain, and a subungual wall of keratin may form. This entity was described some years ago as being caused by formalin in nail hardener. Beau's lines were mentioned, as was "tulip fingers," in which there may be a painful, dry, hyperkeratotic eczema of the fingertips extending under the nails, caused by handling tulip bulbs. There may be dermatitis of the face, hands, and genitals, due to a glycoside which acts as a natural fungistat in the tulip plant. Baran also described subungual exostosis, which occurs twice as often in women as in men, and said the etiology is unknown. Practolol or, less often, propranolol may cause "pincer" or "trumpet" nail deformities. Vertical, striated, sandpaper 20-nail dystrophy (l'ongle gr~se) may accompany alopecia areata or lichen planus. Weed killer and insecticides may cause hypertrophic nail changes with yellow or white proximal color change. Laugier's disease ineludes spotty pigmentation of the lips and oral mucosa and longitudinal single or multiple black striations of the nails. This condition can occur in healthy individuals. Robert Baran spoke on medical, surgical, and cosmetic treatment of nail problems. He classifies onychomycosis into three forms: distal, top of the nail, and nail fold. He gives 1 gm of microcrystalline griseofulvin daily for 6 months for fingernail involvement and 1 gm for 1 year for toenail involvement. The recurrence rate is high, of course. Baran treats onychomycosis occurring principally on the top of the nail by scraping the nail and using topical antifungal agents. In candidiasis

Journal of the American Academy of Dermatology

of the nails with paronychia, the nail tends to turn green and brown. Pseudomonas tends to occur with onycholysis. It is important to keep the nail dry, to use a toothbrush to help apply medications, and to use oral and vaginal nystatin in treatment. He did not mention the possibility of underlying monosymptomatic inverse (volar) psoriasis. For uncommon pathologic fungi he avulses the nail, mentioning two ways to perform surgical avulsion. One way is with the use of a dental spatula, separating the nail distally with the aid of a McKay elevator. He prefers the Cordero proximal technique. With this the nail is incised near its base, elevated, and stripped off distally. For nonsurgical removal of the nails, he uses 50% potassium iodide in lanolin daily, with a plaster, for 8 to 10 days. The treatment can be repeated. He says that it works like urea in separating the nail from its base. For acute paronychia, antibiotics are useless; Baran removes the proximal one third of the nail. We prefer inserting a thin metal spatula or scalpel blade under the lateral or proximal eponychial fold, whereby the pus can be released effectively in most cases without destroying any part of the nail. For chronic paronychia, Baran uses clotrimazole (Lotrimin) topically along with triamcinolone acetonide (Kenalog) spray. For correction of a hooklike nail plate, Baran prefers an excision and applies a split-thickness graft. He showed illustrations of sportsmen's toes (black heel analogue) and of subcutaneous capillary hemorrhage due to shearing stress. He showed examples of washboard thumbnails from overenthusiastic pushing back of the eponychial fold, and also showed an example of Heller's dystrophy. For malaligned nails, he realigns the matrix by excising an ellipse of skin on the side toward which the nail is distorted, making a triangular excision of the eponychial fold on the opposite side and then moving the entire nail and its bed into the new position, followed by suturing. For pachyonychia congenita, he removes the matrix and performs a skin graft. Oral vitamin A acid may also help this condition. He excises ingrown toenails or orthonychia and also excises for DuBois incarnation and for pincer ("trumpet'.') nail. In treating warts about the nails, he applies cantharidin (Cantharone) for 24 hours and repeats it weekly. He also may use 40% salicylic acid plasters or trichloroacetic acid or formalin daily applied with a wooden toothpick. For synovial

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cysts he prefers injection of triamcinolone suspension. POLYAMINES IN PSORIASIS

Michael Proctor of Stanford, the Nelson Paul Anderson lecturer, spoke on "Decreased Levels of Polyamines in Improved Psoriasis." Polyamines are simple linear molecules with a C-N backbone. Once called ptomaines, they include putrescine, spermidine, and spermine. Ornithine gives rise to all three of these. Polyamines bind to DNA. In 1975, spermidine and spermine were found increased in the blood of people with active psoriasis. In 1976, putrescine, spermidine, and spermine were all found to be elevated in the skin and also in the urine and plasma of people with psoriasis. There is a decrease in the levels of these polyamines after successful treatment of psoriasis. In improved psoriasis, putrescine levels in skin and urine are reduced about 50%. Spermidine and spermine are also decreased in blood and urine. Putrescine piles up like water behind a dam in untreated psoriasis. Where does the inhibition occur? Prednisone given for 24 hours inhibits enzymes which metabolize these inhibitors. These include ornithine carboxylase, spermidine carboxylase, and spermine carboxylase. Therefore, we should try using inhibitors of polyamines (when we can obtain them!) in management of psoriasis. They are not yet available. RETINOIC ACID AND CARCINOGENESIS

John H. Epstein, M.D., said that 0.3% retinoic acid cream was found to significantly accelerate carcinogenesis by UVB in hairless mice. Then 0.05% retinoic acid in propylene glycol was tried, and it significantly inhibited carcinogenesis by UVB! H o w e v e r , both 0.01% and 0.001% retinoic acid in propylene glycol have now been found to accelerate carcinogenesis by UVB--only, so far, in hairless mice. Confusion!

MYCOBA CTER1UM ULCERANS INFECTION John H. Pettit, M.D., of Kuala Lumpur, Malaysia, said that since Asian aborigines almost never have gravitational ("stasis") ulcers, and since some cases of leg ulcers appeared to be neither tuberculous nor due to yaws or cobra bites, a search was made in some such cases for Mycobacterium ulcerans--it was found, in abundance, in several instances. The most effective therapy is clofazimine

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(Lamprene), 100 mg tid; rifampicin is equally effective though much more costly. Dapsone and streptomycin are ineffective. Heat is helpful, and immobilization with a window cast is a useful adjunct to therapy. CONTACT DERMATITIS

The next speaker, Niels Hjorth, M.D., of Copenhagen spoke on the most common causes of contact dermatitis. The most common are nickel (46% of patients), chromium (30%), and rubber additives (10%). Nickel is the major single cause of contact dermatitis in Danish women. Ten percent of women in the general population are sensitized to nickel. Buttons in blue jeans are a prime cause of sensitization in Copenhagen. Ear piercing seems to be the most common nickel-sensitizing agent in the United States. Hjorth says that nickel in food is important in keeping nickel dermatitis going, and a low nickel diet prescribed for such individuals results in improvement in half of them. The diet is difficult, and diethyl dithiocarbonate, which binds nickel, can be used in nickel poisoning. This is a breakdown product of Antabuse, and Antabuse can be used in the treatment of nickel dermatitis. Hjorth uses Antabuse (100 mg 3 or 4 times a day) for symmetrical dyshidrotic hand eczema, and the posttreatment test for nickel is negative. There is a negative test to thiuram. Patients must, of course, take no alcohol while taking the Antabuse. The side effects include an initial acute flare, possibly vasculitis. Serum nickel rises. The mechanism of Antabuse is the binding of ingested nickel and the depletion of nickel stores in the body. Kaaber and Menne cleared seven of eleven patients with Antabuse, and only two of the eleven patients were not helped. Chromate dermatitis is seen mostly in builders (50% of cases) and in machinists (18%). Crystalline ferrous sulfate, added to cement, reduces the cN'omium in it. It is cheap. The formula is FeSO4 9 2H~O, and 0.2% in the cement is all it takes to change the Cr ++++++ to Cr +++, which is innoctlOUS.

Epoxies, the monomer and oligomer resins alone, are responsible for 90% of reactions, the hardener (amines) and resins for 9%, and the hardener only for 1%. Epoxy with the low molecular weight of 340 is the main culprit. A product lacking it is a far safer material. Nickel is found in oysters, herring, tea, and whole-grain bread. Formaldehyde is found in

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Shampoos and dishwasher soaps. " B r o n o b o l " is a common offender. IMPORTED TROPICAL DERMATOSES Coleman Jacobson, M.D., of Dallas spoke on "Tropical Dermatoses'Away From the Tropics." The importation of tropical diseases is on the increase---e.g., onchocerciasis, filariasis, and falciparum malaria. There are two types of tropical dermatoses: the acute ones occur in tourists after a short stay in the tropics, and the chronic occur in immigrants from tropical areas. A group of Americans in subtropical Natal, South Africa, in 1973, were exposed to South African tick bite fever. All of sixty-four developed the disease, which included supraorbital headaches and a poxlike eruption. This is referred to in South Africa as " w e e k e n d disease." It is rickettsial and transmitted by a tick. Tetracycline rapidly cures it. Jacobson mentioned a 1-cm vacciniform lesion on the neck acquired in Costa Rica which went on to crusting and ulceration and was found to be caused by Leishmania braziliensis, cultured on NNN medium with demonstration of the leptomonads. Treatment was with cycloguanil pamoate. This drug does not work for Leishmania tropica infections, endemic in the Middle East. From Guatemala came a case of dermatomyiasis. The dermatobium fly (genus Dermatobia) deposits her eggs on a mosquito which in turn infects the new host. The Tumba fly in South America lays eggs in the skin. If one puts petroleum jelly over the spiracles, the larvae come up for air and can be extracted easily with gentle pressure about the wound. This fly possesses small tentacles and has been known to burrow into the brain and cause death. Bilharziasis (schistosomiasis), found in Salisbury, Rhodesia, looks like granuloma annulare histologically, but one sees larvae. Arbovirus exanthem or sindbis is caused by a group A arbovirus, the West Nile arbovirus. The disease, characterized by an efflorescence of macules and papules, occurs in epidemics. It is transmitted by insect vectors. UNILATERAL ACNE Walter F. Schwartz, M.D., of Pasadena discussed unilateral acne vulgaris, a very interesting concept. The basic premise is that the patient creates a microtropical environment, largely because of sleeping habits. People who do notjac-

titate (toss around during sleep) are particularly likely to engender heat in certain skin areas, enabling the acne eruption to appear in an asymmetric distribution such as on one cheek, one side of the back, or one shoulder. Tropical acne has been described by both Sulzberger and Novy, and this is analogous. In 1970, Cunliffe reported the effect of temperature on sebum secretion and mentioned that there is a 10% increase in sebum flow with each degree of temperature rise in the skin. Majorca acne and acne estivalis must be due to a similar mechanism. Other examples would be headband acne, chin strap acne, stretch pants acne, and violinist's acne. SCLERODERMA Asboe-Hansen, speaking on "Connective Tissue Elements in Scleroderma," discussed hormone influences first. With the cortisones, cells are the primary targets: mast cells, fibroblasts, and macrophages. This can be measured with 14C-tagged proline and lysine. Hydroxylation of proline and lysine is inhibited by cortisol, and the cells are inhibited. Dermatan sulfate formation is inhibited, and this in turn results in delayed wound healing. The ground substance is metachromatic. Hyaluronidase is inhibited by cortisol, causing alteration of the ground substance. Staphylococci produce hyaluronidase. Dibenzanthracene tumors (papillomas) in mice are inhibited by cortisone. Carcinomas are inhibited at first, but later the inhibition is lost. Two weeks of prednisone in a dose of 20 to 30 mg daily produces gel-to-fiber ratio changes in the skin, which would normally take 5 years to occur in the ordinary process of aging. MYCOLOGY SELF-ASSESSMENT TESTS Paul Jacobs, M.D., of Stanford gave some excellent mycology self-assessment demonstrations, but they do not lend themselves well to review without illustrations. GRANULOMA ANNULARE Richard Winkelmann, M.D., of Mayo Clinic spoke on " N e w Insights Into Granuloma Annulare." Bleehen wrote of ultraviolet-induced granuloma annulare. An epidemic of granuloma annulare was reported many years ago in Southern California in people who took vitamin D and then sunbathed. Steigleder refers to a reticular epithelial mucinosis, which is really papular mucinosis, which in turn is probably a variant of granuloma annulare.

Volume 1 Number 1 July, 1979

Positive intradermal delayed hypersensitivity skin reactions are histologically indistinguishable from the changes in granuloma annulare. Similar changes may be seen in tuberculosis of the skin, insect bite reactions, changes due to light, familial changes, traumatic changes, rheumatoid changes, malabsorption syndrome, hypervitaminosis D, nodules in Beh~et's syndrome, and diabetes. Most of these reactions are delayed hypersensitivities. The cells are histiocytic and mononuclear and the whole process depends on the lymphocyte. Generalized granuloma annulare resembles sarcoidosis. "Midline mucinosis" in the midback is granuloma annulare. The histologic pattern is histiomonocytic and consisted of three elements: infiltration by these cells, palisading of epithelioid cells, and then epithelioid cell nodules, in fifty-nine cases of sarcoidosis. Five showed cutaneous granuloma annulare, and only fifteen had skin lesions of sarcoid. In sarcoidosis, one sees turned-on macrophages, demonstrable histochemically. There is deposition of fibrin, the hallmark of delayed hypersensitivity, seen on immunofluorescent testing. On EM, one sees monocytes, lymphocytes, and histiocytes with bigh membrane activity. Serum migration inhibiting factor (MIF) is activated, and in both sarcoid and granuloma annulare there are abundant lymphokines. The therapy of granuloma annulare involving tendons and fascia is like the management of S6zary syndrome. Chlorambucil (Leukeran), 4 rag, helped Kossard and Winkelmann's patients for about a year. There was no effect on white blood cells with this dose. This is truly a "biologic experiment" and not therapy per se. Brodthagen recently reemphasized the value of methotrexate for sarcoid. Arnold wonders about the value of Kenalog intramuscularly. One may turn off the blastogenesis response with vinblastine, chlorambucil, or methotrexate. In summary, the granuloma annulare pathology is that of mononuclear cells in a perivascular infiltrating pattern, giving way to histiocytic infiltration and then the formation of fibrin and a granuloma. We still do not know what the aatigen is in granuloma annulare or in sarcoidosis. HOTLINE IN RELEVANT RESEARCH Elaine Orenberg, Ph.D., of Stanford spoke of the "Hotline in Research." In regulation of epidermal growth, phosphodiesterase activates cyclic adenosine monophosphate (cAMP). cAMP controls glycogen. Guanosine monophosphate (GMP)

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initiates the process. Epidermal mediators include catecholamines, prostaglandins, adenosine, isoproterenol, and particularly prostaglandin E. Histamine is also involved. Inhibitors of phosphodiesterase include theophylline, papaverine, 13cis-retinoic acid, and epidermal chalone. If one can increase cAMP, theoretically it should help psoriasis, though there is still no proof that cAMP is low in psoriatic lesions. Prostaglandins modulate cellular cAMP. Prostaglandin F increases cGMP. Prostaglandin E2 gives rise to PGF2~ in essential fatty acid deficiency in rats. Therefore PGFz~ may increase cellular activity. PGEz and PGF2~ are higher in psoriatic plaques than in normal skin. Polyamines are increased when cell growth is enhanced, and are higher in urine of cancer patients. Increase in polyamines is preceded by increase in cAMP. Voorhees and Russell find polyamines higher in psoriatic lesions than in uninvolved areas, and a higher level is present in psoriatic patients than normal persons. Polyamines are lowered by the Ingram regimen,
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Journal of the American Academy of Dermatology

New officers of the Pacific Dermatologic Association (l. to r.) are: Eugene M. Farber, M.D., of Stanford, CA, president-elect; Sheldon A. Walker, M.D., of San Diego, CA, president; Gerald A. Gellin, M.D., of San Francisco, CA, secretary-treasurer; and Thomas Maxwell, M.D., of Bakersfield, CA, vice-president. (Courtesy, Skin & Allergy News.)

melanoma; herpes virus in a suspected melanoma; a fibrous histiocytoma; suggestively invaginated nuclei in suspected mycosis fungoides; same in a S6zary syndrome; diagnostic inclusions in an amniocentesis specimen, permitting antenatal diagnosis of Anderson-Fabry syndrome; diagnostic fibril sizes in different types of Ehlers-Danlos syndrome. It was an impressive tour through the possible uses of EM. Winkeimann, in an aside, said that EM will always be so much more expensive than light microscopy, and will always give such a limited, gun barrel view of the material being examined, that it can never become a very widely or frequently used procedure except for answering very special questions. SOCIOECONOMIC FUTURE OF DERMATOLOGY Thomas W. Murrell, Jr., M.D., of Richmond, VA, recent past-president of the American Dermatological Association, said that expertise makes dermatology viable, but that we are threatened, as a specialty, by several factors. One is national health insurance, which might require referral as a condition of compensation for dermatologic services. There is no imminent plan for this; however, loss of fl'ee choice could be almost as harmful. The increasing tendency to charge regular surgical fees for dermatologic procedures that can be done in a fraction of the time puts us in grave danger of a backlash by third-party payers, however, Dr. Murrell warned. What can we do to protect our specialty's future? Dr. Murrell had several suggestions: I. Be mindful of, and preserve, our unique

skills. They are more precious to us than the skills of other specialties we might acquire. 2. Be primary physicians for cutaneous disease, and let our patients know that this role might be threatened. 3. Resist the expansion of Health Maintenance Organizations (HMOs). 4. See that the public is aware, and remembers, that free choice is a valuable right. 5. Do not encourage the overuse of physician assistants and nurse practitioners. 6. Keep surgical fees within reason, suited to the time and expertise required by the procedure performed. 7. Be attentive to keeping costs down for the uninsured, at least as much as for the insured. 8. Keep training programs at a high level of competency. In regard to the last item, Dr. Murrell might have referred, had he had time, to the current effort by the Federal Trade Commission to force the American Society of Plastic and Reconstructive Surgery to stop requiring American Board certification as a condition of membership. Specialty certification has few enough advantages as it is; if the advantages it has are destroyed by Federal intervention, the Boards may be forced out of business, and with them the only really effective means of quality control for residency training programs in all specialties.

PSORIASIS THERAPY, 1978 Eugene M. Farber, M.D., of Stanford said that Dead Sea therapy is effective, but its conditions are not too difficult to duplicate elsewhere, at less cost.

Volume 1 Number l July, 1979

Low-strength anthralin, he said, is an important, relatively new modality. A concentration of 0,01% to 0.05%, with 10% salicylic acid in white petrolatum, is used! There is no staining. An hour of plastic wrap occlusion is enough. For the scalp, 0.03% with 4% salicylic acid is used, and for the nails, 0.03% with 10% salicylic acid. 5-Fluorouracil, 1% solution, twice daily to the nails for 6 months, according to Fredericksson, "improved" 17 of 20--not a very exciting prospect. For removing hopelessly damaged, thickened nails, 40% urea in anhydrous lanolin with 5% white wax may be applied under occlusion for a week, protecting the nail folds with compound tincture of benzoin, h'ritation is slight, and the nail plate becomes mushy and sloughs off. Orfanos reported that the aromatic 13-trans retinoic acid (Ro 10-9359) orally, 75 mg per day, was only 20% successful after 6 months. Cheilitis occurred in 80%, 43% complained of dry mouth, 30% of scaling, and 15% of pruritus. He feels that oral retinoids should be used only in small doses as a supplement to either anthralin therapy o1"PUVA (Fitzpatrick calls this " R E P U V A " ) . A dose of only 50 mg a day, with few side effects, gave 82% success after 22 treatments. Dialysis, either peritoneal or '~hemo," has cleared half the psoriatics so treated and improved the other half. It is not innocuous: significant complications occurred in 68%, and 6% died. It is not yet practical, only investigative. We are eagerly awaiting the first reports of dialysis against charcoal, with elution and analysis of the dialysate. What is being removed? PUVA is effective. What is wrong with it? Its drawbacks are the following: (1) it is slower than anthralin in most cases; (2) it induces few remiss i o n s - m o s t patients require continuing weekly treatment; (3) it presents still unmeasured risks: carcinogenesis, actinic elastosis, and even amyloidosis in five of thirty patients treated for a year and in five of thirteen treated for 2 years. The risk of cataract from sunlight during the remainder of the treatment day (with psoralens still in the tissues) is probably very real and warrants wearing dark glasses all that day. PUVA should be limited to adults. MINIPRESENTATIONS

The final two hours were devoted to very brief presentations of very unusual cases, some of which are summarized here.

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Thomas W. Murrell presented a case of erythema elevatum diutinum over knuckles and elbows in a chronic arthritic; it cleared promptly during treatment with dapsone. Gerald G. Koehn, M.D., presented a case of prostatic carcinoma metastatic to the glans penis, a phenomenon also seen in bladder and rectosigmold cancer. Michael Franzblau, M.D., presented a case of ulcerating bullous dermatosis of the legs for 1 year in a woman who had diabetes for 30 years. James Graham, M.D., presented a case of perforating morphea, in which the clumping and fragmentation of elastic fibers occurred very deep in the dermis and not near the surface as in elastosis perforans serpiginosa; perforating morphea was considered a secondary type of elastosis perforans serpiginosa. Harry Arnold, M.D., presented two cases of symmetric punctate leukonychia initiated by trauma to one nail and characterized by development of perfectly symmetric white spots on adjacent and contralateral nails within the median nerve area of innervation. One patient had it twice. William Wood, M.D., presented a case ofgranulocytic sarcoma in a patient with chronic myelogenous leukemia, after 9 years' good control with brisulfan (Myleran)--as he said, a curiosity. Edward J. Ringrose, M.D., presented druginduced acanthosis nigricans, which he said might be produced by thiOridazine hydrochloride (Me[laril), lithium, selenium, or diethylstilbestrol; 20% of patients given 2 gm nicotinic acid daily also developed it. Richard B. Odom, M.D., reported the occurrence of Rhizopus infection in a wound after occlusion for 8 days. Clotrimazole cured it quickly. Contaminated Elastoplast (which picks up molds readily) was the source. Stephen W. Skewmake, M.D., said that jejunoileal bypass syndrome, characterized by chills, fever, malaise, and a paputopustular eruption, may occur as long as 5 years after the bypass surgery, may last only 2 to 6 days, and may recur in 1 to 6 weeks. It appears to be an allergic reaction to bacteria such as Bacillus fragilis. Metronidazole (Flagyl) may be very helpful. Michael Klass, M.D., and Lawrence Bass, M.D., reported on a regional epidemic of coccidioidomycosis in the Sacramento area. The epidemic was caused by a storm in December, 1977, which lifted and carried tons of contaminated surface soil fl'om the San ,loaquin Valley north and

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west and dropped it in a previously nonendemic area. Jeffery M. Grant, M.D., described a strange example of what he considers to be a keloid-like papillomatosis which complicated the course of chronic plaque-type pustular psoriasis. The structure of the lesion (which certainly looked like big, globoid keloids) was that of papillomas. It suggested lobomycosis. DERMATOLOGY IN CHINA Robert W. Goltz, who had just returned from a 3-week visit to China as a guest, along with Eugene

M. Farber, of the Chinese government, gave a slide-illustrated account of his visit. He found it generally very impressive, but it is not possible to abstract his presentation here. NEW PDA OFFICERS

New officers of the PDA are: President, Sheldon A. Walker, M.D., San Diego, CA; Vice-President, Thomas B. Maxwell, M.D., Bakersfield, CA; Secretary-Treasurer, Gerald A. Gellin, M.D., San Francisco, CA. The meeting in 1979 will be held in San Francisco, September 17-21.