\ iMlMP:\· II.JI£ MCV/Q ., ,J,\., .. - MEDICAL COLLEGE OF VIRGINIA QUARTERLY VOLUME TWELVE NUMBER ONE 1976 V MED.t JA. �,10,1,,,,_, ,. ,cl9

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... . • ...... • .. •• • • . .. i • ...... , •• I . . . . -. . . . • ' MCV/Q MEDICAL COLLEGE OF VIRGINIA QUARTERLY A Scientific Publication of the School of Medicine Health Sciences Dicision of' Virginia Co11111101111·ea!th University

1976 • Volume Twelve • Number One MEDICAL COLLEGE OF VIRGINIA QUARTERLY Published quarterly (Spring. Summer. Fall. Winter). by the Medical College of Virginia. Division of CONTENTS Health Sciences. Virginia Commonwealth University. The QUARTERLY publishes results or original research in basic and clinical sciences. Contributions rrom out­ side the Medical College of Virginia facul­ TIIE 47T11 A1'1'L'AI. McGuRF LECTURE SERIES ty are invited. Manuscripts. submitted in Co111mo11 Prohle111s in Derma10/ogr duplicate, should be prepared according to recommendations in the Style Manual for Biological Journals. Washington. D.C .. American Institute of Biological Sciences. Second Edition. 1964. Sponsored by the School of' Medicine. Department of'Continuing Edu­ Correspondence: MEDICAL COLLEGE OF VIRGINIA QUARTERLY. Medical cation and the Department of' Dermatology. Medical College of Virginia. College of Virginia. Richmond. Virginia Health Sciences Division or Virginia Commonwealth University. 23298. Phone 804/770-4027. Subscription rates for U.S.A., Canada. W. K1-:,;:,;n11 BLAYLOCK. M.D .. Gue.1·1 Edi1or and Mexico: I year. $6.00: 2 years. SI0.00: 3 years. $14.00. All other countries: I year. $8.00: 2 years. $12.00: 3 years. $15.00. Libraries ctnd institution!>: (US.A.) I year. $12.0U: 2 years. $20.00: 3 .vears. $28.00: (foreign) I year. $13.0U. 2 years. $21.00: 3 years. $29.00. Interns. residents, and student�: I year. $3.00. Introduction 4 Single issue: $2.00. w. KE:s1:s;1-·111 Bi.AYIOCK. M.D. Third class postage paid at Richmond. Virginia.

Ediwria/ Adti.\mT Hoard John T. hrrar i\topic Dcr111atiti, 5 crnst G. Huf K1 :,;:sJJ·Tll B1 ,\)I OCK. M.D. Hunter H. McGuire: w. M. Pinson Neal, Jr. Kinloch Nelson Frederick J. Spencer

Editorial Consultant., Larry F. CavaLos Boston Oral Manil'cstations or Cutaneous Disease 7 Richard G. Lester Durham JA.\ll·S W. 1'1\"ITl·l(SI>N. M.D. Sarni I. Said Dalla., Malcolm E. Turner, Jr. Birmingham

Ediror Fairfield Goodale. Jr. Managing Editor Mary.Parke Johnson l'yot.krmas: Diagnosis and Trcat111c111 11 Cover DPsign Ji\�ll·S J. Li \'1)1 N. M D. Raymund /1. Geary

2 Acne Vulgaris 15 JA'vtES J. LEYDE'I, M.D.

Skin Signs of Systemic Disease 21 ROBERT B. SCOGGINS, M.D.

Cutaneous Manifestations of Venereal Disease 27 CHARLES M. CARA\"ATI, JR., M.D.

Management of Cutaneous Malignancy-A Review 32 PEYTON E. WEARY, M.D.

(i) 1976 by tht' Ml'dkal Coj!('J,:(' of \'irr,:inia, lll'allh Sdl·nct� l>ilh,io11 of \'iq,:i11ia Common"t'itllh llnhnsic,· t'rinted h·y cht• William 8)'rd l'rt'l>�, Rit·hmolld. Vir�ini11

3 INTRODUCTION

The skin is a rather large organ comprising 16% of body weight. It contains several cell types and cell products. Three separate compartments are pres­ ent and a disease may involve one or all. The topmost layer, the epidermis. is a very active metabolic area and disease involving this area is generally acute with oozing, weeping. and scaling. The dermis, which is quite large. gives support to the entire skin and body. Dermal diseases produce swelling, enlargement. and rigidity in the skin. A di.sease in the subcutaneous section of the skin, the third major portion, is usually nodular and edematous. The 47th Annual McGwire Lecture Series en­ titled, Common Problems in Dermatology. presented for the first time lectures in the morning with case presentations in the afternoon to illustrate the prob­ lems discussed. There is great emphasis today on the manage­ ment of common dermatosis by the primary care physician. This is really not new since Osler himself described many skin clues to systemic diseases. The problems presented in this lecture series were those which usually are diagnosed and frequently treated by the first physician who sees the patient. We hope you enjoy this series of papers as much as we enjoyed the presentations.

W. KENNETH BLAYLOCK. M.D. Professor and Chairman Department of Dermatology

4 Atopic Dermatitis

W. KENNETH BLAYLOCK. M.D.

Professor and Chairman. Departmenc of Dermacology. Medical College of Virginia. Healch Sciences Division. Virginia Co1111110111t·ea/ch Uniuersicy. Richmond. Virginia

The term a topic. which means "strange disease." 4. Topical allergens such as nickel and neomycin was first used in 1925 to describe a group of diseases may induce sensitization contact dermatitis in which include allergic rhinitis. bronchial asthma, these patients. urticaria! reactions to drugs as well as food allergies 5. Inhaled allergens probably play little role in or idiosyncrasies. These conditions have in common producing the dermatitis in adults. the presence of skin sensitizing homocytotropic anti­ 6. Emotional feelings may lead to scratching bodies (lgE) in the serum of the person at some point and this trauma may induce the dermatitis. in the natural history of the disease. There is littk Frustration and anger seem to enhance evidence that the dermatitis found in the atopic in­ itching. dividual is produced by lgE which is present in the 7. A factor that has not been given proper at­ serum and skin of the person with atopic dermatitis. tention in the past is bacterial infection and Atopic dermatitis is by definition, then. an in­ bacterial colonization in the skin. flammatory flexural dermatosis of the skin found in Immunology. A specific immunologic defect has the patient who has other manifestations of atopy or not been proven to exist in patients with dermatitis. a family history of these disorders. It is probably the In general. patients with localized atopic dermatitis number one cause of hand eczema in adults. This par­ confined to the hands and feet have a normal serum ticular disorder causes many persons to be rejected lgE level. Patients with generalized atopic dermatitis for military service, and the man hours lost in daily have elevated serum lgE levels. particularly when work due to this disorder are significant. there is exudation and infection in the skin. Patients with an elevated serum lgE level do not Etiology. The specitic etiology of this particular have serum fluctuations with the activity of the dis­ type of eczema is unknown. It is multifactoral derma­ ease whether the disease is minimal or severe. The tosis. These factors include: reason for this serum elevation in generalized atopic I. A genetic susceptibility. dermatitis is not clear. One possibility is bacterial 2. A defective barrier layer in the normal skin infection while another is autoimmunity to an which is accompanied by increased transepi­ antigen such as human dander. dermal water loss from the epidermis with an Clinical Manifestations. The clinical manifesta­ associated increase in absorption of antigens tions of patients having atopic dermatitis are many. into the skin. The normal skin of the atopic The most common are listed below: person may be more easily damaged by ir­ I. The infant usually presents with a dermatitis ritants which include soaps and detergents, on the face. and the extensor surfaces of arms, wool. and other factors. legs, and hips are involved. 3. Sudden temperature changes and sweat reten­ 2. The child who has atopic dermatitis may tion. manifest the eruption first on the dorsal sur­

This is an cdilcd trans1.:ripliun of a lecture presented by Dr. t31.iy­ face of the hands and feet. lock al the 47th Annual McGuire Lecture Series. 16 October. 3. The medial sJrface of the middle finger as 1975. al the Medical College of Virginia. Richmond. well as the small tinger of the hand is a fre-

MCV QUARTERLY 12(1): 5-6, 1976 5 6 BLAYLOCK: ATOPIC DERMATITIS quent site. Accumulation of material around has been outlined. diagnostic confirmatory tests are rings and other jewelry may be the initiating in order. In the patient with a chronic pustular factor in producing this form of the disease. dermatitis of the hands or a generalized dermatitis. 4. The presence of chronic lichenilied dermatitis the serum lgE level may be helpful in separating on the flexural aspects of the arms. legs. and this disorder from other eczematous states. Elevated trunk as well as the hands and feel which serum lgE levels alone. however. are not diagnostic. may lead to exfoliation of the skin. Patch Testing. Appropriate patch tests should be Diagnosis. An important clue in making the performed in order to establish the presence or ab­ diagnosis of atopic dermatitis is a family history of sence of sensitization contact dermatitis. All patients asthma. hay fever. urticaria. or atopic dermatitis. with generalized eczematous dermatitis should have The morphology and distribution of the lesions in patch tests performed to rule out Specific cell medi­ flexural folds is helpful as well as the serum lgE level. ated immunity to a variety of environmental antigens. A history of foot dermatitis as a child. particularly Management. Important modalities in the on dorsal surface. is helpful in establishing the a topic management of atopic dermatit_is include: pattern in a patient suspected of having this trouble­ some dermatosis. This dermatitis on the dorsal sur­ I. The avoidance of a constant exposure to face of the foot in a child is usually atopic dermatitis. irritants as well as excessive water. Gen­ not contact dermatitis or dermatophytosis. eralized bathing should be limited to twice A careful physical examination of the skin lo weekly with intermittent sponge bathing. reveal other components of the a topic skin syndrome 2. The judicious use of systemic antibiotics for will aid in making the diagnosis. These include: bacterial infections is most important. I. The history and physical evidence for recur­ 3. Topical corticosteroid therapy combined with rent allergic rhinitis with or without associ­ partial occlusion especially for hands and feet ated mucosal swelling of the sinuses. is the hallmark of anti-inflammatory therapy 2. Double lines on the face beneath the eyes for atopic dermatitis. Complete occlusion of may be present. the dermatitis with a material such as poly­ 3. Allergic persons with alopic histories fre­ ethylene is to be avoided. quently have a light blue appearance lo the 4. Bath oils and emolienls are helpful. mucous membranes of the nose with an asso­ Careful consideration must be given to the emo­ ciated high. arched palate. tional aspects of this illness. Family members must 4. Cutaneous papules on a dry skin are more receive proper instructions in handling children with common in the alopic patient. this disorder. and the adolescent and adult patient Confirmatory Tests. Once a differential diagnosis will need counseling by the physician. Oral Manifestations of Cutaneous Disease

JAMES W. PATTERSON. M.D.

Department of Dermatology, Medical College of Virginia, Health Sciences Division, Virginia Commonwealth University, Richmond, Virginia

The list of diseases which manifest both oral the major form is occasionally fatal and may warrant and cutaneous pathology is extensive and considera­ the institution of corticosteroids as well as supportive tion of them all is beyond the scope of a single brief local care.' report. Nevertheless, it may be useful to summarize Lichen planus. This chronic papulosquamous dis­ the findings of those diseases in which both oral and ease is of unknown etiology, although viral and neu­ cutaneous lesions are. or can be. significant. Recogni­ rologic etiologies have been proposed, and psychic tion of the one can be a clue to the identity of the factors have frequently been found to be associated other. and evaluation of both skin and mucosa may with the disorder. The eruption of flat-topped. an­ often provide the first evidence of systemic disease. gulated. violaceous papules beginning on the extrem­ The discussion will be divided into two parts: I) ities and favoring flexor surfaces is quite character­ primarily dermatologic diseases with oral manifesta­ istic. though a similar eruption termed lichenoid drug tions: and 2) other diseases in which oral and cu­ eruption occurs with a variety of drugs (antimala­ taneous lesions are prominent features. It will be rials. alpha-methyldopa. gold. para-aminosalicylic limited to a consideration of noninfectious disease acid (PAS). thiazides. tetracycline. and others). processes. Mucous membrane lesions occur in 50% of cases: they may occur in the absence of skin lesions. and· I. Primarily Dermatologic Diseases with Oral they have been observed in drug-induced lichen Manifestations. planus due to quinacrine. PAS. gold. sodium thiosul­ fate and phenothiazines. Lacy hyperkeratotic striae Erythema multiforme is an acute inflammatory on the buccal mucosa and tongue are characteristic. disease of the skin of obscure etiology. although in­ though hyperkeratotic papules and ulcerated lesions fectious and/or allergic mechanisms are suspect. A may also be seen (Fig 2 ). The differential diagnosis of wide variety of predisposing factors has been impli­ oral lesions includes leukoplakia. candidiasis. lupus cated, the most prominent of which are infections erythematosis, and secondary syphilis. though the (herpes simplex, primary atypical pneumonia) and presence of the typical Wickham·s striae and of cu­ drugs (sulfonamides, phenylbutazone). X-ray and taneous lesions help in confirmingthe diagnosis. Cor­ carcinoma have also been associated with the disease. ticosteroids in Orabase"' and topical anesthetics are As the name implies, the lesions are multiform and useful in the management of this condition.' may consist of papules, bullae, and the characteristic Bullous diseases. Certain bullous diseases are target lesions. Oral manifestations a_re seen in the so­ characterized by mucous membrane lesions. Pem­ called "major" type of erythema multiforme and con­ phigus vulgaris and its variant. pemphigus vegetans, sist of vesicles on the lips. tongue, buccal and gingival are notorious for producing oral lesions. They are mucosa which rupture to produce painful erosions present, in fact, in almost every case, and in pem­ (Fig I). The disease tends to be self-limited, although phigus vulgaris, over 50% of patients develop their Presented by Dr. Patterson at the 47th Annual McGuire 1-irst lesions in the oral mucosa. Large, flaccid bullae Lecture Series, 16 October. 1975. at the Medical College of which rupture to leave denuded areas are found on Virginia. Richmond. the lips. buccal mucosa, floor of the mouth, and

MCV QUARTERLY 12(1): 7-10.1976 7 PATTERSON: ORAL MANIFESTATIONS OF CUTANEOUS DISEASE 8 11. Diseases in which Oral-Cutaneous Lesions are a Prominent Feature.

CONNECTIVE TISSUE DISEASES.

Behcei's srndro111e is an uncommon condition of unknow,; etioiogy characterized by recurrent ulcera­ tions of the oral cavity and genitalia and by iritis. Thrombophlebitis. arthralgia. neurologic lesions. and erythema nodosum may also occur.5 It is seen most often in males in the third decade and presents as discreet. punched-out ulcers with erythematous bor­ ders and gray-yellow bases in the oral mucosa. A helpful diagnostic test is the occurrence of a pustule with surrounding erythema at the site of needle prick injury. This occurs 24 hours after injury and is most prominent at the height of an attack. It may be difil­ cult to distinguish oral lesions from those of aph­ thous stomatitis. pernphigus or pemphigoid. and er­ ythema multiforme. Treatments have included antibiotics. gamma globulin. and corticosteroids with or without aLathioprine. all with varying results. The course is usually long and benign. although recurrent uveitis can result in severe eye damage. and neuro­ logic involvement is indicative of a poor prognosis.

Fig I-Blistering and erosions of lips. conjunctiva! invuh crnent. and systemic toxicity in the major form of er) them a multiform\.'..

undersurface of the tongue. On the skin. recurrent crops of Aaccid bullae showing Nikolsky's sign are found in pemphigus vulgaris. Biopsy is useful in mak­ ing the diagnosis, and direct and indirect immu­ nonuorescence are characteristic, showing inter­ cellular binding of lgG3 and complement in stratilied epithelium. Corticosteroids and cytotoxic agents are used in treating this disease. Oral lesions are also seen in bullous pemphigoid and a similar disorder. cicatri­ cial pemphigoid, but they are not seen in another blistering eruption, dermatitis herpetiformis. Psoriasis. Mucous membrane lesions in psoriasis are rarities. but a small number of cases have been reported. Rather rigid criteria must be met in order for a lesion to qualify as oral psoriasis. Lesions must be clearly located on mucosa and not contiguous with skin lesions; they should be found coincidentally with cutaneous lesions and their course should rarallel that of skin lesions. Histologic features are sugges­ Fig 2-\Vhite hypcrkl'ratotic ksiun of the: tongut:: in lichen planus. tive, but only suggestive, of the disease.' Dark spot abovl' g.1u1c is hiupsy sik. PATTERSON: ORAL MANIFESTATIONS OF CUTANEOUS DISEASE 9

Reiter's syndrome is the familiar triad of ure­ Gold toxicity can produce hemorrhagic, ulcera­ thritis, arthritis, and conjunctivitis. Perhaps it should tive, and exfoliative stomatitis. Skin manifestations be considered a tetrad, since mucocutaneous lesions include exfoliative dermatitis and lichenoid erup­ occur in 80% of patients.• Skin findings include hy­ tions. perkeratotic lesions of the palms and soles (kerato­ Methotrexate is a chemotherapeutic agent used derma blenorrhagicum) and psoriasiform plaques on in the treatment of lymphomas, leukemias, and (of the skin and scalp. Oral involvement is seen in up to importance to dermatologists) severe, recalcitrant 40% of cases and presents as painless superficial ero­ psoriasis. Toxicity may develop as shallow whitish sions of the palate. buccal mucosa. tongue. or patches on the oral mucosa, surrounded by erythe­ gingiva. Treatments have included anti-inflamma­ matous borders. Large areas of epithelium may then tory agents, methotrexate. antimalarials. and in­ necrose and slough. Many chemotherapeutic pro­ domethacin. The disease may abate after two to six tocols include the use of folinic acid (citrovorum months or persist as recurrent attacks at varying in­ factor) to counteract methotrexate toxicity. tervals. Sc/eroderma also features oral pathology. Fib­ GENETIC DISORDERS. rosis and atrophy of circumoral skin and widening of the periodontal space are relatively well-known find­ Of the many genetic disorders with oral-cu­ ings.' Less often appreciated are deformation of gin­ taneous manifestations. two have been selected. gival papillae with the formation of granulation tis­ Peutz-Jeghers syndrome consists of mucocutaneous sue in gingival pockets. atrophy of the mucosa with pigmentation and gastrointestinal polyposis. It is in­ prominent venous pattern. and papillary atrophy of herited as an autosomal dominant trait. Flat brown, the tongue, producing the so-called "chicken tongue" black, or blue pigmented spots are seen on the vermil­ appearance. ion borders of the lips. oral mucosa. perioral, nasal, Occasionally (in 10% to 20% of cases) systemic and orbital skin, dorsa of fingers and toes (especially lupus erythematosus is accompanied by oral lesions. over joints). palms. and soles. Though skin pigmenta­ and it should be noted that mucosa! ulcers are one of tion tends to fade after puberty, oral pigmentation the fourteen diagnostic criteria established by the remains for life. Melena and intussusception are the American Rheumatism Association (ARA). 8 Lesions chief complications. It is important to note that, al­ may appear as pinpoint atrophic areas with keratotic though malignant change of small bowel polyps is margins and surrounding hyperemia. Petechiae on rare. there is an increase in incidence of cancer above the palate, buccal mucosa, gingiva, or tongue develop the ligament of Treitz and in the colon.' into shallow, painful ulcers with gray, necrotic bases. Neurojibromatosis is also inherited as an auto­ somal dominant trait. The occurrence of multiple DRUGS. cafe au lait spots in neurofibromatosis is well known. Four to 7% of cases have oral involvement with single A number of drugs may be responsible for oral or multiple tumors, usually on the tongue. Malignant as well as cutaneous lesions. Antibiotics may induce degeneration of neurofibromas is uncommon but toxic responses in the mouth as a result of distur­ does occur in 2% of patients and presents as a variant bance of the ecologic balance of microflora. Black of fibrosarcoma. ' 0 hairy tongue is an example, in which elongated, stained filiform papillae are noted. Frequent use of METABOLIC DISORDERS. oxidizing agents or excessive smoking have also been associated with this condition. Cutaneous pathology in Addison's disease con­ Gingival hyperplasia develops in I 0% to 35% of sists of diffuse pigmentation accentuated on exposed patients treated with sodium diphenylhydantoin. This surfaces, sites of friction, palmar creases, and scars reaction occurs independently of dose or duration of which have developed during adrenal insufficiency. drug, and results from fibrosis beginning in the inter­ The oral pigmentation is spotty in appearance and dental papillae. Diphenylhydantoin has also been as­ may occur in advance of other characteristics of the sociated with a number of cutaneous eruptions, in­ disease (Fig 3 ). The pigmentation results from in­ cluding an acneiform variety, bullae, and exfoliative creased output of beta-MSH from the pituitary, un­ dermatitis. Hypertrichosis is also observed. checked by the normal adrenal-pituitary feedback. 10 PATTERSON: ORAL MANIFESTATIONS OF C TANEOUS DISEASE

ythema of exposed areas. This burning, itching erup­ tion desquamates to leave deep pigmentation and eventual atrophy. A necklace of dermatitis (Casal's necklace) and seborrhea-like dermatitis of the nose (dyssebacea) are other characteristic findings. Oral disease includes an intense stomatitis. involving the tongue. gingiva, and palate. and reddening and ulce­ ration of the lips. Pellagra today is often seen as part of a multiple nutritional deficiency state in alcoholics and chronically ill individuals. In conclusion. this brief discussion includes only a few of many disorders in which oral and cutaneous manifestations play a prominent role. It emphasizes the importance of a thorough oral-mucosal exam­ ination in the evaluation of any perplexing cutaneous disease.

REFERENCES Ln, 1 A: Ervthema multiform. in Fitzpatrick TB et al (eds): Dermarology in General 1\1edicine. Ne" York. McGraw-Hill Book Company. 1971. pp 598-608.

2. ARnt-,Rn HO: Stom:Hologic manifest;Hions of internal and intcgumental disorders: Lichen planus. in FitLpatrick TB et al (eds): Dermatulogy in Gt'neral Afedicine. Ne" York. McG ra \\­ Hill Book Compan, . 1971. pp 937-940.

3. SAMS \VM JR: lrnmuno!luorescence in dermatology. in Mal­ hg 3-Spott) hyperpigmentation of the gingiva and hard palate in kinson FD. Pearson R\\' (eds): Yearbook of Derma10/ogy a p..iticnt \\ith Addison·s disease. 1973. Chicago. Yearbook Medical Publishers Inc. pp 19-22.

Addisonian buccal pigmentation may be difficult to 4. AKCll·\RD HO: Stomalologic manifestations of internal and a c distinguish from that of normal dark-skinned indi­ integumental disorders: Psori sis. in Fitlpatri k TB et �11 (eds): Dermawlogy in General .\Jedi<'ine. Ne \\ York. McGra,, -Hill viduals and from PeutL-Jeghers syndrome, but other Book Comp.111)·. 1971. pp 941-942. clinical features should aid in making this diagnosis. 5. Cllo\Jl·h. T. F,\l'\-\RL M: Bch�e1·s disease. Report of -JI cases NUTRITIONAL DISORDERS. and a rcvic" or the litcralllrc. A1edicine 54:179-196. 1975.

A discussion of oral-cutaneous disease would 6. P1·HH\ HO: Reitcrs syndrome. in Fit,patrick TB et al (eds): not be complete without a consideration of nutri­ Dermarology in General Afedicine. Ne,, York. McG raw-Hill Book Companv. 1971. pp 2.16-249. tional deficiency diseases. Ariboj/auinosis manifests as glossitis and cheil­ 7. DoMo:-.:Ko\ AN: .·1ndrt·1,·s· Diseases of the Skin. cd 6. Philadel­ V osis. Glossitis results from atrophy of the parillae of phia. I B Saunders Company. 197i. pp 184-1�:i. the tongue, along with dilatation and proliferation or the capillaries and concomitantly slowed circulation. 8. D1-ci,..1-1< JL. I· I -\l. Systt:mic lupus aythcmatusus-corllrasts The latter accounts for the tongue's characteristic <1111d comparisons. (NIH Lt.rnfcrcrH.:t:) Ann /111 Aini 82:391-404. magenta color. Cheilosis describes the denuded. red­ 197). dened appearance of the lirs at the line of closure and 9. BRAVl:RMAN IM: Skin Signs oj Sysu,mic Disease. Philadelphia. V maceration at the angles of the mouth. Seborrheic I B Saunders Company. 1970. pp 31 <; • .J f7. accumulations around the nose are also seen. The cutaneous features of are familiar, o pellagra 10. Li Vl·K WF. SC"IIAU.IIIIUHCi-Ll·\TH G: Hi>lopaiho/ogr or lhe consisting of photosensitivity manifested by er- Skin. Phil.itklphia. J P Lippint..:ott Company. 1975. p 6J5. Pyodermas: Diagnosis and Treatment

JAMES J. LEYDEN, M.D.

Assistant Professor of Dermatology, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

The diagnosis and treatment of cutaneous in­ lescing superficial bullae which rupture easily and fections appear to be rather straightforward al first leave behind a thin varnish-like crust. This eruption is glance. Major texts of pediatrics and dermatology usually seen in children. most commonly on the face. indicate that the vast majority of pyodermas are due although any part of the body may be involved. Fever to either Staphylococcus aureus (S. aureus) or and other systemic signs are infrequent. Therapy con­ Streptococcus pyogenes and that antibiotics are cura­ sists of oral antibiotics. either penicillin G 400.000 tive. On closer scrutiny, however, one quickly be­ units q.i.d. for ten days or oxacillin 500 mg q.i.d. if a comes aware that there is a great deal of nomencla­ penicillinase producing organism is involved. Local tural confusion with a corresponding lack of clarity care of compresses and topical antibiotic or ster­ regarding therapy-particularly on the point of oid-antibiotic creams are useful. This form of pyo­ whether or not topical antibiotics have any place in derma is rather contagious. but does not carry with it therapy. the potential for post-infection glomerulonephritis. Pyodermas can be divided into two main classes: A severe and fortunately rare form of S. aureus primary and secondary. In a primary pyoderma. the infection is the toxic epidermal necrolysis syndrome. skin is normal or at most has suffered a minor cut. A toxin mediated by phage type 71 S. aureus causes abrasion, or insect bite. In such a situation. the in­ widespread necrosis of the epidermis and results in a vading organism is entirely responsible for the clini­ sloughing off skin. producing the so-called "scaled cal picture. The situation is entirely different in a skin syndrome." The infecting organism is usually in secondary infection. Here the underlying process is a the nasopharynx. ear. or conjunctiva and not in the chronic inflammatory process, for example. atopic skin. Treatment consists of intravenous penicillin dermatitis which first becomes colonized, usually by (Nafcillin 50 mg/kg) until the lesion ceases to appear S. aureus. and secondary infection is present only and then oral Nafcillin for seven to ten more days. when S. aureus has proliferated to rather high levels Streptococcal pyoderma begins as superficial (see below). vesicles. but quickly erodes and develops a central Primary Cutaneous Infections. ulceration with a thick crust and an areola of er­ Two distinct forms of primary pyodermas have ythema surrounding the ulceration.' These lesions been described: I) Bullous impetigo caused by Group occur primarily on the lower extremities of children II S. aureus usually phage type 71. and 2) Streptococ­ during the hot, humid summer months and are fre­ cal pyoderma or ecthyma due to Group A beta he­ quently associated with lymphadenopalhy and fever. molytic streptococci. Both have distinctive clinical Streptococcal skin infections do not result from the characteristics which can allow confident diagnosis. strains responsible for throat infections and anti­ Bullous impetigo presents as multiple, often coa- slreptolysin-0 (ASO) titers are feeble. although an­ tibody response lo other streptococcal antigens (DA N-ase B and hyaluronidase) can be vigorous.' From the University of Pennsylvania. Derartment of Derma­ Cultures reveal Group A streptococci under the crust tology. Duhring Laboratories. Hospital of the University of Penn­ sylvania. 3400 Spruce Street. Philadelphia. Pennsylvania 19104. and under the edges of the advancing ulceration while

MCV QUARTERLY 12(1): 11-14.1976 11 12 LEYDEN: PYODERMAS: DIAGNOSIS AND TREATMENT the crust itself may reveal only S. aureus. Treatment been fully established as yet. Pseudomonas certainly studies in both humans and in hamsters support the appears to be relatively virulent. but the density re­ view that streptococci are the important agents since quired to aggrevate an underlying dermatosis and the presence of penicillin-resistant staphylococci in the density of Escherichia coli IE. coli). Proteus, and mixed lesions does not interfere with effective treat­ others have not been elucidated. These organisms can 3 ment with penicillin G. ·' It is this streptococcal vari­ be found in low numbers in wet body areas such as ety of pyoderma which carries the risk of post-in­ the groin. axilla. and toe space. and at low numbers fection glomerulonephritis. There are no studies these organisms do not damage intact human skin. demonstrating the prevention of glomerulonephritis Present evidence would suggest that a useful guide­ by penicillin treatment and in fact there is consid­ line would be that if a culture reveals the predo111i- erable clinical evidence to suggest that renal com­ 11a111 organism to be a gram-negative. then it most plications may occur despite penicillin treatment.' likely is contributing to the clinical picture. The Treatment consists of benzathine penicillin 2.4 choice of an antibiotic would be one that would in­ million units intramuscularly for extensive deep­ clude activity against the gram-negative isolated. seated lesions.• The role of topical antibiotics is un­ 3. Candida a/hicans. settled. Several studies comparing topical to systemic Our experience with this organism in experi­ therapy concluded that systemic therapy was supe­ mental infection situations has taught us that it is rior. However. no attempt was made to separate extremely toxic to human skin. A far lower inoculum deep. extensive lesions from the early more super­ is needed to induce an infection than with any other ficial variety. Our own view is that in early lesions. organism we have studied to date. For example. as compresses and topical antibiotics are quite effec­ low as ten Candida cells will result in a severe reaction tive.' after three to four days of growth under saran wrap Secondary Infections: lmpetiginization. while thousands of cells and prior suppression of the Inflamed skin provides fertile soil for bacterial resident nora are required for experimental S. aureus overgrowth. and it is not surprising that dermatitic infections.• ' 0 The isolation of C. albicans from a der­ skin can become colonized and then infected with matitis such as diaper dermatitis is therefore a very various pathogens. In most cases. the organism in­ signilicant linding. and anti-yeast measures are in­ volved is a S. aureus. A variety of phage types are dicated. found. but rarely are the highly virulent strains such 4. Propio11ibacteriw11. as type 71 isolated. Beta hemolytic streptococci are Two main groups have been identified: P. acnes rarely recovered from dermatoscs: in several hundred which is susceptible to P. acnes bacteriophage is more studied cases we have found five examples of Group prevalent and found in greater densities in the se­ A beta hemolytic streptococci complicating an under­ baceous areas than is the phage-resistant P. gran­ lying disorder-two were in epidcrmolytic hyperkera­ ulosu111. Recovery of this organism from a skin cul­ tosis and the other three occurred as severe "athlete's ture does not indicate an infection. rather it is a foot" infections.' Candida a/hicans and gram-nega­ member of the resident llora. This organism does. tives are found in two situations. namely in derma­ however. appear to play a central role in acne vul­ toses occurring in wet body regions and in patients on garis. Acne patients carry a much greater density of long-term antibiotic therapy. this organism than do aged-matched controls." The The question arises of when does the recovery of current hypothesis is that this organism influences the an organism from a dermatosis indicate infection is acne process by virtue of production of free fatty present and that antibiotic therapy is indicated. acids through hydrolysis of sebaceous gland triglyc­ Through our quantitative studies we have to date erides. Those antibiotics which lower P. acnes in vivo evolved to an understanding of the r·ollowing guide­ such as tetracyclinc. erythromycin. and clindamycin lines for interpretation of routine non-quantitative arc also Judged to be useful in the management of culture reports. acne. while penicillin and sulfonamides neither lower I. Normal Aerobic llora-non-pathogcns. P. acnes nor help in the treatment of this disorder. To Staphrlococcu.1· cpider111idis ( S cpidem1idi.1 ). lipo­ d;1tc. wc have not encountered P. ac11es resistant to philic dipthcroids. ;1ntibiotics. and clinical failure during antibiotic ther­ 2. Gra111-11c!{atiues. apy does not indicate that another factor is involved. Thc rclativc virukncc ol. thcsc organisms has not for example. hormonal disturbance. emotional dis- I.EYOF.l\: PYODFRMAS: DIAGNOSIS ANI> TREATMENT 13 tress. or other factors. To dale. only systemic antibi­ rnralive be,ause invading pathogenic bacteria are re­ otics have heen round to lower P acnes levels. Re­ sponsible for the entire clinical picture. Local com­ cently. however. there is some evidelll:e suggesting presses lo n;move crusts and topical steroids to sup­ that topical henLoyl peroxide may he an effective prcs, rnlaneous inllammation are useful adjuncts. agent ror suppressing P. acnes. hut the main thrust of therapy is lo remove the of­ :i. S. (/1/J'<'l/S. fending pathogen. S1aphrlococrns aureus is the usual organism re­ In secondarily infected dermaloses. a variety of covered from in Ila med skin. A \'ariety or phage types therapeutic approa,hes are available and often sev­ are reco,·ered: ,·irulenl strains su,h as type 71 are not eral modalities must be simultaneously utilized. Both fre4uenl. In a series or studies. we ha,·e established topical and systemic antibiotics are effective. and that a density or one million S. aureus organisms per ,hoi,e is determined principally by the extent and s4 <.:111 is the le,·el al ,,·hich antibiotic therapy ,,ill severity or involvement. Steroids are indicated for produ,e clinical improvement." Our definition or a suppression or the underlying inllammalory condi­ S. aureus secondarily infe,ted dermatosis is thererore tion. whi<.:h promotes a more normal skin and the expressed in quantitative terms. Certain eruptions rar return of the normal tlora. The combination of ster­ more commonly harbor levels or S. aureus e.,ceeding oids and antibiotics appears to offer a rational ap­ our established quantitative criteria for presence or a proa<.:h. secondary infection. In atopic dermatitis. as many as 1 n excessively wet areas such as the axilla. groin. 45", of even the chronic li,henilied ,·ariety and I ooc; and toe web space. and in severely exudative lesions or the acute exudative form will harbor more than a anp,·here. therapy must also include "drying" million S. aureus per sq cm. In such cases. even agents. Excessive moisture promotes bacterial growth though overt clinical signs of infe,tion are lacking. and must be controlled in order to obtain satisfactory topical or systemic therapy will produce a rapid sup­ results. Tht: use or compresses is often indicated. pression of this organism in one week's time and Dyes such as gentian violet and Castellani's paint result in clinical improvement. Other conditions fre­ which have both astringent and antimicrobial activity quently harboring more than a million S. aureus per provide a double-pronged approach. sq cm include numular eczema. neurodermatitis. ex­ The object of therapy should be to restore the foliative erythrodermas. and chronic ramilial benign skin to a nonintlamed status and to promote return of pemphigus. and again antibiotic therapy will orten be the normal protective residenl microtlora. Antibiotics useful in these conditions. In psoriasis and seborrheic are used to remove pathogens. steroids suppress in­ dermatitis. S. aureus very rarely achieves a high llammation. and compresses remove excessive mois­ enough density lo be clinically signilicant. and antibi­ ture. Successrul therapy involves attacking all aspects otic therapy is rarely useful except when S. aureus of a disorder. growth has been stimulated. which can happen. ror example. during occlusive therapy with impermeable RHERENCES plastic film. An important corollary of this principle of the quantitative aspect of S. aureus secondary in­ 1. DAJA�I t\S. Ft:RRll·RI P. WASSA'.\1AKl·R L\V: Natural history go. II. Etiologic agc.:nh and h,1ctcrial intcr,11.:tions. fections is the role of steroids in such conditions. One of impc.:ti J C/i11 /11res/ 51 :286.1-2X71. 197". might predict that topical steroids could lead to an aggravation of a condition heavily coloniLed with S. .., WA;-..:NA.\11\Kl·R L\V: Medical progress: Differences hct\,t.:cn strcplth.:nn:al inft.:t..:Lion�of the.:throat and of the skin. tv· t.'ngl aureus. Clinical experience does not support the the­ J � ('(/ 2X2:2 .1-.1 I. 7X-X5. 1970. ory. however. The explanations for this apparent par­ adox is that topical steroids are effective in suppress­ J. DHU{H h. C\V. 011111:-- IIC JR: Further :-.tudics nn the trcal- l ing the inllammalion which promotes S. aureus 1111.:111 nl' :-.tn.:pll1L'lH.:1:al :-.kin infcl.:tion. J Pediatr 77:(1 J6-700. coloniLation and proliferation. By removing the con­ 1970. ditions favoring S. aureus growth, the return of the 4. DAJANI AS. H11 1 PL. WAN/\'.A�IAKl;R LW: Experimental in­ normal protective flora is promoted rather than S. fection or the skin in the hamster simulating hum,111 impetigo. II. t\ssc:-.smcnt or variou:-. therapeutic regimens. overgrowth. Pediatrio aureus 4X:X.1-90, 1971. Therapeutic Approaches. In primary infections such as bullous impetigo, 5. LASCII EE. FKANKFt V, VARDY PA. FT Al· Epidcmil.: glomc:­ ecthyma, and cellulitis, systemic antibiotic therapy is ruloncphritis in Israel. J /11fec1 Dis 124:141-147. 1971. 14 LEYDEN: PYODERMAS: DIAGNOSIS AND TREATMENT

6. ALLEN AM. TAPLIN D. Tw1GG L: Cutaneous streptococcal 10. SINGJJ G. MARPLES RR. KuGMAN AM: Experimental staphy­ infections in vietnam. Arch Dermatol 104:271-280. 1971. lococcus aureus infections in humans. J Invest Dermatol 57:149-162. 1971. 7. LEYDEN JJ. KuGMAN AM: Rationale for topical antibiotics. JAMA. to be published. 11. LEYDEN JJ. MCGINLEY KJ. KLJGMAN AM: P. acnes in acne and non-acne subjects. J Invest Dermatol 65/4:382-384. 1975. 8. LEYDEN JJ: Antibiotic usage in dermatological practice. Int J Dermatol 13: 342-352. 1974. 12. L1-Y1JF� JJ. MARPU-s. RR. Kt.1GMAN AM: Staphylococcus 9. REBORA A. MARPLES RR. KLJGMAN AM: Experimental in­ aureu.f in the lesions of atopic dermatitis. Br J Dermarol. fection with candida albicans. Arch Dermatol 108:69-73. 1973. 90:525-530. 1974. Acne Vulgaris

JAMES J. LEYDEN. M. D.

Assistant Professor of Dermatology, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Acne vulgaris displays all the characteristics of' a strated a decrease in lamellar granules (membrane polygenic disorder in that hereditary factors are ap­ coating granules. Odland bodies).' A decrease in parent with strong family tendencies for the disorder membrane coating granules with comedo formation while the phenotypic expression of the disease varies suggests that these structures may act as lysozymes over a wide spectrum. All that is known for certain and promote cell separation and not function to keep concerning the genetics of acne is that concordance is cells together as "cementsomes" as proposed by extremely high in identical twins. 1 In the past dec­ Hashimoto.• Further studies on the dynamics of ade. various investigations have resulted in much comedo formation and the ultrastructural changes clearer concepts of pathogenesis and have brought us which result in failure of separation of horny cells are to the point of effective therapy for the majority of needed. The developing comedo surfaces clinically cases. In this report. I will summarize recent concepts tirst as a "whitehead" in which the surface opening is in the pathogenesis of acne vulgaris. microscopic and then bulges above the skin surface as a "blackhead." The color is due to melanin pigment I. Acne H istopathogenesis. produced by melanocytes which are found in the The histopathogenesis of acne involves two main upper 20% of sebaceous follicle epithelium.' pathways: I) impaction and distension of sebaceous A mature comedo is thus several millimeters follicles by tightly packed horny cells and 2) disrup­ deep and firmly entrenched. Attempts to dislodge tion of the follicular epithelium allowing discharge of these lesions by vigorous. abrasive washing in hu­ the follicular contents into the dermis which then mans and in experimentally induced lesions in the induces an inAammatory reaction. 2 The clinical coun­ rabbit ear model fail dismally. The significance of this terparts of this process range from the non­ area of research to the clinician is that vigorous wash­ inAammatory comedo to inAammatory papules. pus­ ing is of little use in acne therapy. Former concepts of tules. and nodules. obstruction at the follicular outlet which could be The sine qua non of acne is the formation of relieved by frequent washings and use of "peeling" comedones. Ordinarily the epithelium lining the ca­ agents were grossly incorrect. Such theories do not nal of sebaceous follicles produces keratinized cells stand up to the overwhelming evidence that com­ which are sloughed and carried to the surface in a edones represent an impaction of the follicular canal stream of sebum. Comedo formation begins when with a solid mass of horny cells. Comedones are deep follicular horny cells begin to stick together. As structures and successful therapy can only be horny cells fail to dehisce. an expanding solid mass achieved by altering the abnormality in follicular ker­ accumulates and dilates the follicle. Recent electron atinization. Retinoic acid's mechanism of action in­ microscopic study of the dynamics of comedo forma­ volves its effect on keratinization. As a side effect. it tion confirmed these observations and also demon- can produce "peeling" and dryness. but this is unre­ lated to its mode of action. In the treatment of both experimentally induced comedones and naturally oc­ From lhe University or Pennsylvania. Duhring Laboratories. De­ partment of Dermatology. Hospital of the University of Pennsyl­ curring lesions. retinoic acid induces the formation of vania. 3400 Spruce Street. Philadelphia. Pennsylvania 19104. horny cells which no longer stick together.• Inhibiting

MCV QUARTERLY 12(1): 15-20. 1976 15 LEYDEN: ACNE VULGARIS 16 the synthesis or quality of the cement substance uating antibiotic therapy in acne. Antibiotics do not which binds horny cells into soli-d impactions thus induce pu-s.tules and papules to resolve. Rather they attacks the disease at the very point of origin. work in an indirect way to minimize formation of Acne becomes an inflammatory process when new lesi·ofil.s. the comedo ruptures. Disruption of the foHicular.- wall II. Bacteria and Acne. i . may be partial or comple\e. The seve,rity of ·the Clinii;• '1st lh:rs i.ol1!g tjeen recognized by clinicians that cal lesion correilates directly with ! he extensiveness of syst�mic antibiotics are beneficial i11 the therapy of the rupture and ranges, from a segmental disorganiza­ inflammatory acne. but it is not until relatively re­ tion of follicular epithelium. resulting in a quick-heal­ cently that the role of bacteria has been. studi·ed. ing pu.stule. to major breakdowns and dissolution Three kinds of organisms are· constantly found and formation of a de-ep indolent nodule. in the sebaceous-rich areas and they constitute the Rupture is not- a consequence of simple pressure. normal resident microllora of all persons, regardless Neutrophils first col'lecl along the border of the fol­ or the presence or absence or .acne.' They include: I) licle, usually in a ci.rcumscribed fashion. and then the yeast Pityrosporun: 2) aerobic coagulase nega­ invade the epithe-lium. inducing spongiosis and cellu­ tive cocci: and 3) the anaerobic diphtheroid now lar degeneration and f.inally rupture of the follicular ollicially classilied as Propionibac{erium acnes (P. epithelium.' A derma;l abscess consisting l'irst of leu­ arnes). The aerobic cocci and Pityrosporu.n are mainly kocytes and l·ater .mO'nonuclear cells and giant cells located superticially near the orifices of sebaceous then develops. Partial' ruptures heal by resorption follicles. Propio11ihac1eriw11 arnes inhabits the depths and the horny impacte• :\l mass remains in situ. In of the follicle and there is comi-derable. evidence moderate-sized rup-turis:, the severed ends of epithe­ implicating this organism in the pathogenesis of in- lium send out sheels of undifferentiated cells which 11ammalory acne. undermine and reincapfulate the abscess analogous I. Large numbers of P. acnes accumulate in fol­ to the healing proccysts.' Massive rupture-of developing comedones results 3. P. acnes produces substances capable of in­ ducing comedo forma'tion- in the rabbit ear in the foll.icular- conle·nts·. being literally extruded into the dermi.s, and a viole0ht inf1ammatory reaction re­ model.' sults which is seen dinically as a tender, erythe­ 4. P. arnes is responsibl.e for the liberation of matous papule or nodul.:. These lesions are deep and free fatty acids which are comedogenic and can persist for wee-ks as a foreign body granuloma capable or inciting pronounced inflammatory 9 replaces the initial, absce·ss.' reactions. ·w The significanc.ti of these insights in the 5. In the absence or P. acnes, inflammatory le­ pathogenesis of inflammatorylesions rests in the fact sions are not seen. Corned.ones provoked in that pustules. papules,- and nodules actually represent the rabbit ear never rupture because they are an injlammatoty proi.ess and not an infectious one sterile: coal tar and chloracne are pre­ despite the similarity. of the lesions to pustules and dominantly comedonal. The antimicrobial furuncles caus.ed by S1aphylococcus aure,us .. , {,S. activity or those a.gents prevents the develop- aureus). The faG'l !hat an acile n·od,wl·e re�re:s'ei'/i'f.5i an< -I.;,;_ ·. \, nle,rit di,', i,\(l, anu11;.1tory: lesions.' (l , int1ammatory process acctturi•is fg.r i!oie 5. t[ t,i\i,0C iht ' ,)f\ i\,,�lihioii�. · such as tetracycline and eryth- lralesional corticostero'id lhe.rapy. H l .ti�Se iesi>v ��:­ 1 •. · ' HJi,l1yci11 whit:li suppres-s P. acnes are benefi­ were infections, steroid injectiof.l. ·w6uld·s:urely\,or. sen. ' .Jial in ther.apy, while others such as penicillin the condition. S ,irnih1racne conglobata is markedly decreased and often completely eliminated. excessive oiliness. Acne does not make its debut until The nose and nasolabial folds are the areas of max­ pre-puberty when sebaceous glands start to enlarge imum fluorescence and easiest to examine. If these under the influence of adrenal hormones. This pre­ areas still fluoresce heavily after a month of systemic pubertal onset of acne coincides with enhanced sup­ antibiotic therapy, then incomplete intestinal absorp­ plies of cortisol and adrenal androgens accom­ tion of the antibiotic is likely. The second technique panying adrenal gland maturation. Cortisol appears involves measurement of the degree of resistance of to act in a rermissive fashion in two ways: I) Corti­ the surface aerobic flora to the antibiotic a patient is costeroids are known to augment the action of test­ 16 11 taking. Normally the surface aerobic cocci show little osterone on androgen-sensitive tissue, · 2) corticos­ (less than 20%) resistance to tetracyclines, erythromy­ teroids potentiate the follicles· ability to undergo cin, and clindamycin. After two to three weeks of retention hyperkeratosis and form comedones.' With therapy, approximately 80% of the surface aerobic the onset of gonadal function and testosterone pro­ flora will be resistant to a systemically administered duction. a f'urther increase in sebum secretion occurs antibiotic. 11 By quantitatively culturing the surface and acne severity increases. While adrenal and go­ aerobic flora on media with and without added anti­ nadal hormones are prerequisite to development of biotics, one can rapidly estimate the degree of resist­ sebaceous gland size and function, all studies indicate ance. If the antibiotic has not been absorbed, the that acne patients have normal circulating levels of 1 surface flora will not have developed a high degree of androgenic hormones. '' No difference exists even resistance. Quantitative cultures provide precise data, when the most severely afllicted are compared with but even semi-quantitative analysis, easily done by appropriate control subjects. Enlarged sebaceous 18 LEYDEN: ACNE YULGARIS glands and overproduction of sebum seem therefore are not as maximally stimulated as those of men and to indicate an end-organ sensitivity. In fact a recent any increase in circulating androgens will have a pro­ study does suggest that the sebaceous glands of acne portionally greater effect. The ultimate expression of patients metabolize testosterone to the metabolically this factor occurs in women and is often referred to in more active dihydrotestosterone at a 111 uch greater texts as pyoderma faciale. Actually. this is an ex­ 1 rate than those of non-acne subjects. • Such a finding plosive form of acne almost exclusively seen in supports the hypothesis of end-organ sensitivity and women. Classically. a severe emotional stress pre­ explains why testosterone blood levels are not higher cedes the onset of marked seborrhea which is then in acne patients. This study suffered. however. by rapidly followed by the onset of deep nodular and not matching controls to sebum production. and pustular lesions. This form of acne is extremely diffi­ until such studies are performed. the inviting concept cult to control. and in addition to the usual thera­ of end-organ sensitivity to normal levels of test­ peutic maneuvers. some form of tranquilizer or seda­ osterone is not yet proven. Future investigations of tion is necessary. this end-organ hypersensitivity promise to reveal U/1raciole1 Lighl. Most dermatologists would basic secrets of the acne process. agree that ultraviolet light is helpful in acne therapy. Currently. researches are being made for topi­ Acne patients in general appear to improve in the cally effective agents which act to produce a local summer. However. such improvement may more ac­ suppression of sebum production. If an agent or curately reflect seasonal variation in the disorder agents can be found which are free of systemic effects. which is unrelated to ultraviolet light. Recently. Klig­ a major advance will have been made. man and Mills have incriminated ultraviolet light in IV. Miscellaneous Factors. that erythemic radiation actually enhances the com­ Dier. No evidence exists to incriminate dietary edogenic activity of materials such as coal tar and factors. The few studies on this subJect have all come free fatty acids in both humans and in the rabbit-ear 19 0 to the conclusion that diet does not play a role. ·' model." Further work is needed in this area to dis­ Dietary restrictions do not constitute rational meas­ cern just what happens to the acne patient who ures in an anti-acne regimen. spends his summer on the beach and appears to im­ Fric1ion and Trauma. Once one understands the prove and require less therapy. evolution of an inflammatory lesion. the adverse ef­ Cos111e1ics. Many cosmetics including cleansing fect of friction is apparent. Repeated trauma to a creams and moisturizers contain chemicals which can follicle. distended by an impaction of horny cells. aggravate acne. 22 The mechanism appears to be that promotes rupture of the follicular epithelium and the of inducing the derangement of keratinization which formation of new inflammatory lesions. The common results in horny cells sticking together and eventual sources of friction include overzealous washing. par­ impaction or the follicle. Cosmetics do not produce a ticularly with abrasive soaps. habits of leaning on or physical obstruction of the follicular orifice. rather rubbing an area of the face. pressure from helmets. the mechanism appears to be due to a chemical in­ tight collars. wrestling. and other contact sports. At duction or comedo formation. The follicular epithe­ times, local physical factors can be severe enough to lium is induced to form horny cells which stick to­ the degree that usually effective therapy appears at gether and eventually result in comedones. best to be merely containing the process instead of Therapy. suppressing the formation of new inflammatory le­ With the basic concepts of pathogenesis as out­ sions. Failure to perceive the role of friction often lined above. our approach to acne therapy is as fol­ leads the therapist to switch from one antibiotic to lows: another in a fruitless search for the "best antibiotic." 1. Diel. No evidence exists to substantiate the Emo1ional Fae/ors. While rigorously controlled common belief that certain foods aggravate studies with endocrinological monitoring have not the acne process. Dietary restrictions are use­ been done, there is general agreement that emotional less and ineffective. factors can play a significant role. The probable 2. Skin care. Acne patients are oily and want to mechanism is the production of adrenal androgens remove the objectionable feel that excess oil which lead to increased seborrhea followed by crops produces. No "special soaps" are necessary. of inflammatory lesions. Women appear to be more Patients should be instructed to wash gently susceptible, possibly because their sebaceous glands two or three times daily to remove surface oil, LEYDEN: ACNE YUi.GARiS 19

but under no circumstances should they scrub nesis to insure confidence and cooperation with the or abrade their skin. This leads to an in­ now quite successful therapeutic maneuvers avail­ tensification of the inflammatory aspects of able. acne. Blackheads are 4 mm deep and cannot REFERENCES be washed away-as most acne patients even­ tually discover. Local friction to the acne I. NIERMANN H: Bericht iiher 230 Zwillinge mit Hautkrankhei­ areas is to be avoided at all costs. tcn. Z 111enschl Vererb Konsrirlehre 34:483. ( 1958). 3. A primary and perhaps the central thera­ 2. KI.IGMAN AM· An overview of acne. J Invest Dermatol peutic maneuver involves the topical use of 62:268-288. 1974. retinoic acid (Retin-A') which reverses the abnormality in follicular keratinization. This J. KrsuTso;-.; A: Ultrastructural observations in acne vulgaris. material is applied once daily to the entire The normal seb�iceous follicle and acne lesion. J Invest Derma­ area of involvement. not just to clinical le­ rol 62:n8-308. 1974. sions. Application must be only to bone dry 4. HASHIMOTO K: Cementsome. J new interpretation of the mem­ skin (no closer than 15 minutes to the last brane-coating granule. Arch Der111a10/ Forsch 240:349-364. facial washing) to avoid unnecessary local ir­ 1971. ritation. Patients who also have atopic der­ matitis may be able to apply this agent only 5. BLAIR C. LEWIS CA: The pigment of comedones. Br J Derma­ 82:572-58.l. 1970. once or twice a week. Retinoic acid unseats rol existing comedones in 8 to 12 weeks and pre­ 6. KL1G'1A!\ AM. Fu, TO!\ JE. PLEWIG G: Topical vitamin a acid vents the formation of new lesions. As such it. in acne vulgaris. Arch Dermarol 99:469-476. 1969. is the backbone of acne therapy. It is contin­ ued till the patient is free of new lesions for 7. MARPLES RR:The microllora of the face and acne lesions. J lnL"es/ Der111a10/ 62:326-332. 1974. several months and then slowly withdrawn. 4. Antibiotics are indicated for patients who 8. LEYDE>I J. MCGINLEY K. K1.1GMA>I AM. Propionibacterium have moderate to severe intlammatory le­ kvcls in the race of acne and non-acne subjects. J Invest sions. Tetracyclines and erythromycin have Dennarol. to be published. been time-proven safe and efficacious choices. 9. K1 l(i.\l,\� AM. KATZ AG: Palhogenesis of acne vulgaris. I. The usual dose is 500 to 1.000 mg/day in Comedogenic properlies of human sebum in lhe external canal divided doses initially and then gradual with­ of the rabbit. Arch Der111a10/ 98:53-57. 1968. drawal as inflammatory lesions disappear. In combination with topical retinoic acid, most 10. STRA�SS JS. Poc111 PE: lntracutaneous injection ofsebum and patients will not need antibiotics for more comcdones. H islological observations. Arch Derma to! 92:4-1.1--156. 1965. than 3 or 4 months. More recently. properly formulated topical antibiotics have been in­ 11. MARPLES RR. K LIGMAN AM Ecological effectsof oral antibi­ troduced. Currently, there are several formu­ otics on lhe microllora of human skin. Arch Dermatol lations of benzoyl peroxide which are ex­ 103:148-153. 1971 tremely effective. Many patients, however. 12. KRUGER G. CHRISTIAN GL: Clindamycin vs. placebo as ad­ cannot use both benzoyl peroxide and reti­ junclivc therapy in moderately severe acne. Arch Dermatol noic acid simultaneously because of excessive 111:997-1001. 1975. local irritation. More recently, 2% erythromy­ cin free base has been shown to be effective, 13. FULTON JE. WEEKS, JB. MELARTY L: The inability of a bacte­ but it is not yet readily available. rial lipase inhihitor to control acne vulgaris. Read before the Society of lnvestig

ROBERT B. SCOGGINS. M.D.

Clinical Associale Professor of Derma1ology, Medical College of Virginia, Heallh Sciences Division, Virginia Conm1onll'eallh Universily, Richmond, Virginia

The subject or this McGuire Lecture series. the They may be grouped by pathogenetic mechanisms. skin. is a relatively enormous organ vulnerable to an by organ systems. or by various conventional cate­ enormous variety of external and internal insults. Its gories of disease. Some of the skin findingsare rather total visibility is both a blessing and a curse. Its very nonspecific and some may appear in a variety of size and the protean nature of its disorders may para­ associations. while others may be very specifically doxically make it easy to ignore: it may so overwhelm related to a disease state. the neophyte that he is discouraged from the proper First. let us consider some disorders grouped by training of his retina. organ system. those neurocutaneous syndromes with A famous and wise Chicago dermatologist. Dr. rather specifically associated skin lesions. Neurofi­ W. A. Pusey. wrote many years ago ...Skin diseases bromatosis is a classical example: we all can recog­ occur on the surface of the body. where everyone can nize from a block's distance the patient with dozens see them but few recognize them." Indeed. there is to thousands of varying sized and shaped soft tumors often a great gulf between seeing and recognizing. that tend to invaginate the skin when pressure is seeing and comprehending. For example. I wonder applied ( .. buttonholing"). We know that this patient how many of us have passed the site of these lectures may also have neuromas wherever neural tissue is numerous times and failed to recognize the distinctive found in the body. that there is a 2% to 5% incidence abstract mummy design of the cast iron fence posts of malignant degeneration of those tumors, and that outside? Or how many of us have somehow missed there may be other associated defects. We know. too. knowing about the significance of this landmark that the patient will have numerous macular areas of Egyptian Building in American architectural history'l hyperpigmentation called cafe au lait spots, and will Our powers of recognition are easily overwhelmed by also have axillary freckling. There will be little help to all of the other buildings. people. and traffic around offer this patient. Had we been able to diagnose the here. just as our recognition of skin disorders and disorder in infancy, we might have prevented the their significance may be impaired by the plethora or birth of a younger sibling who would also have the things that can appear upon the skin. disease. Therein lies the greatest significance of the In this lecture. I want to point out a few impor­ cafe au lait spots: 5% to I 0% of the normal popu­ tant landmarks on the skin that should attract our at­ lation may have one or a few. and such spots are also tention no matter what else is around, lesions we found in Albright's syndrome. but the presence of six should be able to select out of the morass of 600-odd or more spots of greater than 1.5 cm diameter and of skin disorders to warn us that something may also be the freckling is almost pathognomonic of Reck­ amiss elsewhere in the body. There are numerous linghausen's disease. and they may be found early in ways of classifying these dermadromes. these associa­ infancy. Informing the parents of the dominant in­ tions of skin pathology with pathology elsewhere. heritance of this disorder may properly dissuade them from further childbearing. Knowing the diag- · nosis may also give ready explanation for bizarre Presented by Dr. Scoggins al the 47th Annual McGuire Lec­ neurological findings that can appear, sometimes in ture Series. 17 October. 1975. al the Medical College of Virginia. Richmond. the relative absence of skin tumors.

MCV QUARTERLY 12(1): 21-26. 1976 21 SCOGGINS: SKIN SIG ·s OF SYSTEMIC DISEASE 22 Another neurocutaneous syndrome in which freckles are so vividly described by Shelley as early recognition is of crucial importance in genetic .. entrance signs to tell us there are polyps counseling is tuberous sclerosis. Patients with this within'"' The benign ha111artomatous polyps may be disorder also may have a few cafe au !ail spots. but anywhere in the bowel (and also in the nose. bronchi. the significant dermatologic l'inding is at the other and genitourinary tract). They get the patient into end of the pigmentary spectrum: 90%, or these trouble because of intussusception or bleeding: recog­ patients will at birth have macular hypopigmented nition of the skin freckling may readily explain the areas of varied size and contiguration. some of them trouble when one is confronted with a patient who with a characteristic ash leaf outline. Examination has unexplained abdominal colicky pain or melena. with a Wood's lamp facilitates their discovery in Despite the benign nature of the polyps. these light-skinned individuals. Early in life these "hite patients do have a greater-than-normal tendency to patches (they are not true vitiligo: some melanocytes develop carcinoma of the colon and stomach. There are present) may be the only cutaneous manifesta­ is also a I O"f incidence or ovarian tumors in women tions. because the lesions of adenoma sebaceum. un­ \\'ho have the PeutL-Jeghers syndrome. gual and gingival fibromas. and shagreen patches Another useful "entrance sign" is found in the appear much later. Here again is a dominantly inher­ Rendu-Osler-Weber syndrome. in which superficial ited disorder in which early recognition and proper telangiectases of the skin signal the presence of sim­ parental counseling may prevent further tragedy. ilar lesions in bowel as well as other internal struc­ Here also is a clue to otherwise unexplained neuro­ tures. Again. recognition of the skin component pro­ logical phenomena: a child with these light spots and vides immediate explanation for internal bleeding. A unexplained seiLures very likely has tuberous scle­ further vascular association is the correlation of spi­ rosis. der angiomas and red palms with the failing liver. A Considering the neural crest origin or mela­ most specific correlation. this time involving unex­ nocytes. it is not surprising that yet another neurocu­ plained occlusion of s111all blood vessels. is found in taneous disorder. ata.,ia-telangiectasia (Louis-Bar Degos· disease (111alignant atrophic papulosis). The syndrome) occasionally displays hyperpigmented and atrophic. porcelain-11hite skin papules surrounded by hypopigmented macuks. Here. however. they are not a telangiectatic border are matched by similar bowel the leading clues to the diagnosis. Rather. the appear­ (and other organ) lesions which are prone to per­ ance of telangiectases of the skin. particularly in sun­ forate and cause death from peritonitis within a short exposed areas. and of the cornea provides the diag­ time of onset of this rare disease. nosis in the patient who has cerebellar ataxia and Cutaneous signs or endocrine malfunction are choreoathetosis. That patient will also have recurrent unparalleled for playing the ga111e or diagnosing­ sinopulmonary infections. related to his low levels of from-thc-foot-of-the-bed. Few things can be as lgA (and. in 30%. of lgG ). which may cventually grossly visihlc as the striae. atrophy. acne. hypertri­ cause his death. if he does not die sooner of lymph­ chosis. moon f'acies. and buffalo hu111p or Cushing's oma. Genetic counseling is or lesser importance here. syndrome. or the cool. dry. puffy. carotenemic skin this disease being inherited in a n::cessive fashion. and thc loss of hair (including sometimes the lateral but earlier recognition may benefit the patient by one-third of the eyebrows) of hypothyroidis111. In causing heightened awareness and more cffectivc rnntrast. the hyperthyroid patient exhibits ,,arm. management of the complicating illnesses. moist. soft. smooth. !lushed skin which is occasion­ Structures as contiguous and continuous as skin ally overlaid with acne papules. distal onycholysis and gut could well be expected to share close disease ( Plummcr·s nails). hyperpigmentation and even viti­ associations. The most dramatic example is pyo­ ligo: hair groll'th may also decrease. More dramati­ derma gangrenosum in which the painful. chronic cally. the hyperthyrnid patient. 111ost likely after skin ulcers are counterparts or gut ulceration. most trcatment. may develop llesh-colored or erythe- ol'ten ulcerative colitis (50% ). but sometimes also re­ 111atous or bro\\'nish nodules or plaques ,in the shins gional ileitis or even gastric and duodcnal ulceration. and clsc,,·here. callcd pretibial llr localized 111yxe­ It is worth noting that thc skin ulccr may precedc dcma. Thc sa111c patient usually has exophthalmos. clinical evidence of the bowel lesions. Another clear­ l'aticnts with diabetes mellitus also have a pro­ cut association is found in Peutz-Jeghers syndrome. pcnsity to devclop pretibial lesions of two types. One. dominantly inherited. in which acral and periorilicial nccrobiosis lipoidica. is characterized by sharply de- SCOGGINS: SKIN SIGNS OF SYSTEMIC DISl'I\SI' 23

marcated. brownish-yellow. atrophic areas. Sixty-five flammatory plaques with atrophic centers, the ex­ percent of patients with necrobiosis lipoidica have panding red borders, and the follicular plugging of overt diabetes. Of the remainder. three-fourths have the characteristic discoid lupus erythematosus lesion abnormal glucose tolerance tests or a family history can be readily recognized. It is most reassuring to be of diabetes. The second type or lower leg lesion is able to tell the patient he has only a 1% to 5% chance found in 46% of diabetics and is characterized by of ever developing the systemic form of the disease, smaller brown, somewhat atrophic patches called but discoid and systemic lupus truly form a contin­ "brown spots" or "diabetic dermopathy." The spots uous spectrum and the possibility of development tend to look like ordinary trauma scars. but probably must always be remembered. The availability of the represent yet another manifestation or diabetic mi­ LE cell test and antinuclear antibody determinations croangiopathy. There is a multitude or other visible have greatly aided in the differentiation. At some problems associated with diabetes: lipodystrophy: ex­ point in their disease history. as many as 83% of coriations because of itching: carotenemia: ulcers and patients with systemic LE will have skin lesions. Fif­ gangrene: Dupuytren's contracture: bacterial. mo­ teen percent will have what appear to be typical dis­ nilial. and dermatophytic infections; acanthosis nigri­ coid lesions. only one-third will ever have the "but­ cans: hirsutism: vitiligo: idiopathic bullae: xan­ terfly rash" (most patients we see with something in thomas: flushing and anhidrosis as complications of the butterflydistribution have only seborrheic derma­ neuropathy. Then. there is "bronze diabetes": he­ titis or rosacea), and some will have only what may mochromatosis. Therapy of diabetes introduces other be passed off as sunburn or urticaria. The skin lesions problems. ranging from localized and systemic reac­ of dermatomyositis may be equally vague to the care­ tions to insulin preparations through photoderma­ less observer. and the prime clue is again the distribu­ toses induced by oral hypoglycemic agents. tion. Another helpful sign in both systemic lupus and The photodermatoses occupy a niche or particu­ dermatomyositis is periungual telangiectasia. Either lar clinical and research interest in dermatology. of these diseases may at some time exist in a crossover There is always one great clue to their diagnosis: the form with sclerodermatous manifestations, but distribution of the dermatosis must be in sites ex­ scleroderma is not a photodermatosis. Scleroderma·s posed to light. Beyond that. the differential diagnosis many manifestations, including turgid. bound-down may be tedious and taxing. because one must con­ skin. telangiectasia. and hyperpigmentation. occur sider all the topical and systemic agents capable of without respect to light exposure. producing a light eruption. the entities such as poly­ Let us now consider that most nonspecific of all morphous photodermatitis and solar urticaria that cutaneous indicators of systemic disease: pruritus exist unto themselves without known cause or sys­ without primary skin lesions. The great problem is temic consequence, and the several diseases with in­ always to rule out a primary dermatosis. because its ternal correlates which may be triggered or worsened hallmark may have been eradicated by the ex­ by light exposure. Pellagra is a classical example or coriations. abrasions. lichenification. crusts, and ec­ the last group: we still expect to see it every spring chymoses superimposed by the uncomfortable when the poorly nourished emerge from their hiber­ patient's hands. One must always consider partic­ nation to enjoy the warmth of the sun. but find them­ ularly dermatitis herpetiforrnis. glass fiber dermatitis. selves developing acutely inflammatory skin lesions. scabies and other infestations. and simple dry skin, perhaps even with bullae. Those with any variety of which will be the most common cause of unexplained porphyria other than the acute intermittent form find itching in the winter months. Psychogenic causes will themselves similarly afflicted. explain the problem in another large group of Two of the collagen vascular diseases, lupus er­ patients. Once the foregoing have been considered ythematosus and dermatomyositis, are notable for and eliminated, and the itching is unresponsive to the development of characteristic lesions as a result or usual measures. the clinician must proceed to careful sun exposure and indeed for having internal manifes­ physical and laboratory evaluation of other possi­ tations worsened by that exposure. Although only bilities. Pruritus may be associated with and may be 40% of lupus patients are at any one time photosensi­ the presenting symptom in a variety of disease states: tive, one cannot readily know which patients will be internal neoplasms: diabetes mellitus: chronic renal so or when. Therefore, all must be carefully taught failure; hepatic disease; hyperthyroidism and, rarely, that sun is poison. The well-circumscribed in- hypothyroidism; polycythemia vera; systemic lupus SCOGGINS: SKIN SIGNS OF SYSTEMIC DISEASE 24

Fig I-Partial and lOlal .inonychia in paticnl with dyskcratosis congl!nita.

erythematosus; paraproteinemias; juvenile rheuma­ Some of the genodermatoses in particular are of such toid arthritis; parasitic infestations; certain nutri­ complexity that many years of study by multiple in­ tional deficiencies; gout; neurological disease includ­ vestigators are required to unveil the whole picture. ing tabes, thalamic tumors, pre-eruptive herpes Even then, the discovery of a basic defect. that one zoster, and the syndrome of hereditary localized pru­ hopes is correctable. often awaits the discovery of ritus. Drug history must also be evaluated: itching some new piece of basic biochemical or physiological may be the only evidence of drug allergy or may knowledge. For example, we were asked several years precede the obvious eruption; cocaine and opium ago to see a patient on another service because of her derivatives are pruritogenic; amphetamines can in­ peculiar fingernails. This teen-aged girl had been hos­ duce repetitive picking and scratching of the skin. pitalized for treatment of a recurrently fractured fe­ Like urticaria, erythema nodosum, and erythema mur. Her fingernails were most unusual, being par­ multiforme, unexplained itching must be considered tially to totally absent (Fig I). Further examination a symptom complex, demanding a foray into the revealed a distinctive pattern of reticulated hyperpig­ etiological forest. mentation of the skin (Fig 2), intraoral patchy hyper­ Certain syndromes involve such a multiplicity of pigmentation and leukokeratosis. poor dentition. organ systems that they defy easy categorization. sparse hair. palmar and plantar hyperkeratoses. ab- SCOGGINS: SKIN SIGNS OF SYSTEMIC OISEASI' 25 sent dermatoglyphics. and absent lacrimal punctae. She also had chronic. refractory pancytopenia. This constellation of findings added up to the diagnosis or a very rare disorder. dyskeratosis congenila. More investigation uncovered five other involved family members in three generations and some previously undiscovered unique features: dominant inheritance. chromosomal abnormalities. and certain immunolog­ ical defects.' Studies of this family have involved dermatologists. orthopedic surgeons. hematologists. biochemists. immunologists. radiologists. patholo­ gists, and geneticists. Despite all of these studies. we have not yet uncovered a basic unifying defect. Nei­ ther have we been able to offer much therapeutic benefit. One family member has died of carcinoma. another eventual component of this disorder. and another has died of accidental injuries. his death probably being related in part to his profound throm­ bodytopenia. To offer a more successful example. Dr. Lowell A. Goldsmith, a dermatologist-biochemist al Duke University. has recently shown what therapeutic ben­ efits may grow from careful observation and study of a similarly rare disorder. Earlier he had found rather serendipitously that patients with the Richner-Han­ Fig 2-Distinctivc rat tern of rctil..'ulatcd hypcrpigmentation \\ ith hart syndrome had extremely elevated plasma tyro­ intcrspcr..;t:d isbnds ()fnorrnal ;ind h�popigmcnted skin in dyskcra­ sine Jevels.3 At a regional dermatology meeting last tosis congcnita. year he found an infant who had the typical findings of herpetiform corneal ulcers that eventuate in blind­ lance. for perhaps the most important functions of ness. punctate palmar and plantar keratoses so pain­ medicine after all are to reduce the annoyance of ful that they limit use of hands and feet. and mental common alllictions. make our brief passage more retardation. This child had plasma tyrosine levels comfortable. palliate in the highest sense. fifty times that of normal. Following biochemical There is. nevertheless. a peculiar excitement gen­ logic. he placed the patient on a low tyrosine-low erated by the recognition of a skin lesion that imme­ phenylalanine diet. Now. several months later. this diately tells us that something. perhaps very specific. child has normal vision and healed keratoses. which in a Jess accessible site may also be diseased. Even should allow normal walking and development of the more exciting is the realization that the whole saga is lower extremities.' It isn't every day we enable the not and never will be written. Any of us on any day blind to see and the lame to walk. but it is the hope of may have the opportunity to recognize a new correla­ that sort of result that keeps us inquisitive. tion between skin and systemic disease and. as a In concluding this review of some dermadromes. result. may be able lo do more to benefit the patient I do not want to leave the impression that it has been who has the disease. comprehensive. Many other skin-systemic disease 1 correlates may be pursued further in genentl'- " and specific reference sources. Neither do I want lo leave REFERENCES the impression that we dermatologists devote most of our practice hours to diagnosing such rare enlilies as I. Slll·I I l·Y WB: ('rmsultafions in Dermarologr II. Philadelphia. W l:l Saunders Company. 1974. p 98. tuberous sclerosis or Degas' disease. On the contrary. we expend most of our efforts on the common derma­ 2. SnH;c;1:,..,1s RH. P•nsco1 r KJ. /\s111·1< GH.1-1 At Dyskerall)Sis toses which fortunately have no relationship to dis­ congcnita with F,rnconi-typc anemia: investigatinns of immu­ ease elsewhere. That does not lessen their impor- nolngil· and other dcfccts. abstracted. C/in Res 19:409. 1971 26 SCOGGl:'JS: SKIN SIGNS OF SYSTEMIC DISEASE · J. Grn D\\11111 Li\. K ·\'<, I:. B11-"\1-,,c, DC. 1-1 ,1 · T� rn:-.inc.:mi,1 7. hi/1'\IHIC, TB... ,""" KA. C1 ._., 11 H Js. 1-·1 ·\I (eds): \\ ith plantar and pal mar kcratusi:- and J..cratiti:-.. .I P<'dimr Oama10/ug_r in (it'naa/ .\ledicinC'. Ne.:,, York. McGr�m-Hill 8.1:798-805. 197.1. Boo\.. Compan�. 1971.

-L Go11,.,,1. 1111 L•\. Rt·l·ll J: T�ru:-.inc-indu1.:c.:d c.:�1:. anti ,\..in lc.::-.inrh in human:-.: .'\ tn:atahlc gcnl'lk di:-.ca:-.c.:. J:l.\l.-1.l ) X. l)( ,,i« ,, h.( J\ :\ i'\': A m/n·11·., · Oisea.H'., n) the Skin. cd 6. Phila­ be puhli,hed. lh:lphi:1. \\'l3 Saunder, Cnmpan�. 1971.

5. Jofl.\:\()' S led): The S/...in a11d lnl<'ma/ Di.H'W<'. Ne,, York. 9. Dl·\11" DJ. I I ,1 (t.:d..,): Clinical Dermatology. Hagerstown. rvh:Gr;rn-Jlill Boo\.. Compan� 1967. J/;1rpt.:r & Rn\\ Puhli:-.ht.:r:-. lnc ll)7-:,_

6. BK,, 1 K\\,, I �I: SJ..i11 Sign, of S_1·s1c111ic /Ji.,<'a.w. PhibJdphia. HI. ,\I""< 111 tr, SI.. P11 1 "BL K\ IJ�L HL Kl I·\ HJ (t.:d:-.): Derma· \\'B Sau111..kr.., Com pan�. 1970. rolug_i- Philalklphia. \\"l3 Saundt.:r:-. Cvmpan�. 1975. Cutaneous Manifestations of Venereal Disease

CHARLES M. CARAVATI. JR , M.D.

Clinical Assistant Professor of Dermatology. Medical College of Virginia. Health Sciences Division. Virginia Commonwealth University. Richmond. Virginia

There has been a dramatic increase in the inci­ what he has. Diagnosis under these circumstances is dence of venereal disease. and these disorders have not difficult. become one of our major national health problems. The problem is the female who is asymptomatic It is obvious that if this chain of infection is to be in many instances.' She has only mild vulvovaginitis broken. individuals with these diseases must be treated or cervicitis. and she has very little in the way of as early as possible in the course of the infection symptoms. It is obvious that she will not be treated before there is a chance for it to spread to others. We unless the physician makes sure that she is through have been implored to help tind the sexual contacts of his treatment of her male contact who presents with these individuals, and it is essential that we use the symptoms. Internal involvement may occur with this excellent epidemiological investigators of our health disorder in the form of progression of the organism departments for this purpose. to the internal genitalia resulting in salpingitis. Some­ From the physician's viewpoint. it is particularly times this may lead to pelvic inflammatory disease important to recognize these disorders early and treat and sterility. them as soon as possible, and in order to do this we There are very few lesions on the skin and need to recognize the lesions we see. Many of these mucous membranes. Rarely. there will be localized disorders have their first manifestations on the skin cutaneous lesions in and around the genitalia. These and mucous membranes, and our purpose is to pre­ may involve the lower abdomen. the upper medial sent a somewhat panoramic view of the many and thighs. and the genitalia themselves. and may take the varied types of skin lesions that may lead to the form of pyoderma-Jike infections. These lesions may diagnosis of one of these disorders. appear as folliculitis or abcesses. The first part of this discussion will deal with About I% or 2% of individuals with gonorrhea, gonorrhea because it is the most common of venereal if left untreated. will develop generalized cutaneous diseases. It not only has the highest incidence among gonorrhea.3 These lesions usually begin as erythe­ venereal diseases, but it has also become one of the matous macules and progress to papules or vesiculo­ most common of all infectious diseases. There were at pustules (Fig I). They most frequently are located on least two and a half million cases in the United States the distal extremities and sometimes take on a hem­ last year.' The disorder usually begins with genital orrhagic appearance. Organisms reach this destina­ infection and in the male is a relatively simple prob­ tion apparently by hematogenous spread, and these lem. There is urethral discharge, marked dysuria. and lesions are commonly associated with fever and arth­ the patient is so uncomfortable that he rapidly pre­ ralgia. The arthritic involvement most frequently oc­ sents for treatment. Most of the time he even tells you curs in the large joints, particularly the knees. wrists. and ankles. The typical hemorrhagic papules on the distal extremities though few in number should be Presented by Dr. Caravati at the 47th Annual McGuire Lecture enough to suggest this diagnosis without any of the Series. 17 October. 1975. at the Medical College or Virginia. Rich· mond. other lindings. but if they are accompanied by fever

MCV QUARTERLY 12(11: 27-31. 1976 27 CARAVATI: CUTANEOUS MANIFESTATIONS OF VENEREAL DISEASE 28 and arthritis, the diagnosis is almost certain, and it is located on the penis, frequently on the glans or on the basically a clinical one. Unfortunately, Neisseria area of the coronal sulcus. They have a clean base, gonorrhea usually cannot be cultured from the cu­ slightly rolled edge, and are firmly indurated if pal­ taneous lesions, but frequently can be identified by pated with the gloved hand of the examiner. Typical means of fluorescent staining techniques.' Therefore, lesions in this area are readily suspected. Most of us we have to depend on the clinical combination of would immediately think of primary syphilis. On the these three manifestations, and sometimes a culture other hand, the primary lesion in the female is most can be obtained from the cervix of the female. frequently on the cervix, and if it is not suspected and While gonorrhea actually has very little in the an examination with a vaginal speculum is not done, way of findings on the skin, syphilis probably has it will be missed.' In addition, the lesion may appear the most varied number of cutaneous lesions of any as almost any nonspecific type of erosion. The second infectious disease. The primary phase has an in­ most common location of lesions in the female is on cubation period which averages about three to six the external genitalia. weeks. but may stretch all the way from ten to ninety Another problem is the increasing incidence of days. The firstsign is an indurated papule which soon extragenital primary lesions. These do not occur on becomes eroded and leaves an ulcer. Most patients the genitalia, but may occur anywhere on the anat­ will have regional lymphadenopathy or so-called sat­ omy. They are frequent in the perianal region, and ellite buboes. In the male, most of these lesions are this is particularly true in our ever-increasing homo-

Fig 1-Hcmorraghic vesicopustulcs or generalized cutaneous gonorrhea. CARAVATI: CUTANEOUS MANIFESTATIONS OF YFNl'RFAI. DISh'\SF 29 sexual population.• These lesions may appear as al­ TABLE I most any nonspecific erosion of the anal area, ap­ Cutaneous Lesions of Secondary Syphilis pearing to be an anal fissure or erosion. Another common extragenital location is the perioral region Annular Maculopapular including the mouth, pharynx. lips, and tongue. Split papules PuslUlar Paln.wr and rlantar Follicular Again. because of the location, many would never Alopccia Squamous suspect the diagnosis of even a classical lesion. Extra­ M ucnus pah.:ht:-" Pigmented genital lesions can occur in rare locations such as Condylomata l..ila Nodular fingers where they are sometimes seen in medical, Marni'ar Rupial dental, and- paramedical personnel. Papular Ulcerative Secondary syphilis is by far the most varied cu­ taneous phase. The incubation period is a great deal triginous areas particularly around the genitalia and longer. and the patient is not as suspicious of any in the perianal region. These lesions are flat-topped contacts he may have had because the average in·­ and this appearance helps to differentiate them from cubation from the time of infection to the beginning the pointed lesions of condylomata accuminata or of the secondary phase is somewhere around two to venereal warts which may occur in the same area. three months and may be as long as six months. Condylomata lata may become quite massive and be There are sixteen different types of cutaneous lesions surrounded by marked hyperemia, and if a dark field listed in Table I. and the main point to emphasize is is done from these lesions, it is readily positive be­ that almost any type of cutaneous lesion can occur in cc1use they are mois.t• and usually teem with spiro­ the secondary phase of syphilis. The one major ex­ chetes. ception to this rule is that in adult secondary syphilis Annular lesions- are among the most character­ vesicles and bullae rarely. if ever. occur.6 istic type for this phase of syphilis. These are lesions Some types of lesions are more characteristic with an active advancing border and a healed center. than others. Annular lesions, split papules. palmar Th-ey may occur in other disorders such as sarcoidosis and plantar lesions, alopecia, mucous patches. and or granuloma annulare, but once again, if they are condylomata lata fall into this category. seen. secondary syphilis should be included in the The patient in Figure 2 has an erythematous differential diagnosis. Split papules may occur at any macular, morbilliform type of eruption which could crevice such as along the corner of the nose. behind an easily be mistaken for a drug eruption or any viral ear. or at the- corners of the mouth where they may be exanthem. A V DR L was reactive at I: 128. Lesions on diflicult to separate from perleche. Mucous patches the palms and soles are probably the hallmark of are white stuck-on-appearing lesions that may occur secondary syphilis. These lesions may take any form: o-n :my mucous membrane such as the cervix or oral macules, papules, pustules, and even an exfoliative area. Sometimes these lesions are difficult to differen­ process may be seen. Most of them are hyperpig­ tiate from hchen planus. moniliasis. and even leuko­ mented macules with an overlying fine white scale. plakin. but they may be much more impressive with pustules Because of its varied forms of presentation. leading almost to exfoliation. If one sees a patient with secondary syphilis is often confused with several lesions on the palms and soles that are symmetrical o-ther disorders. Pityriasis rosea is one of the most and are not vesicular or bullous, this diagnosis should difficult to separate from secondary lues. A patient at least come to mind. who does not have the classical herald patch and Alopecia is usually described as being patchy in the classical Christmas tree distribution of pityriasis nature or, classically, as being moth-eaten in appear­ rosea. is suspect. The palms and soles should be ex­ ance.• Once again, almost any patchy type of alopecia amined and if they are clear, the patient probably should be suspected. There are some exceptions to does not have syphilis, but the physician should be this rule, and probably the most common type of thinking about the possibility and a serologic test patchy alopecia is alopecia areata. However, without should be done.' a ready explanation or diagnosis such as alopecia Having talked about the so-called major vene­ areata, the physician should consider secondary lues. ri:al diseases bi:cause they have the highest incidence, Condylomata lata begin with flat-topped pap­ I would like to turn 1he discussion to those that are ules which coalesce to form masses, usually in inter- sometimes considered minor. but are certainly not CARAVATI: CUTANEOUS MANIFESTATIONS OF VENEREAL DISEASE 30

Fig 2-Palmar and plantar lesions are extremely suggestive of secondary syphilis. minor to persons who have them. Chancroid has the field examination and negative serologic tests. If these so-called soft chancre, as opposed to the hard chancre are not done, the clinical diagnosis of chancroid can­ of syphilis, because it is not usually indurated. The not be made.' lesions are multiple and extremely tender and all of Next, are two disorders which are frequent.ly these characteristics help clinically to separate it from confused because their names are similar: lympho­ syphilis. The lesions are usually located on the gen­ granuloma venereum and granuloma inguinale. They italia, and most of these patients will have inguinal really are not very much alike except that they occur adenopathy. The ulcers frequently have a dirty, ne­ on or around the genitalia. Both are considered to be crotic, shaggy base. They are extremely tender and venereal in nature. In lymphogranuloma venereum, because there is so much necrosis they may emit a the primary lesion is a papule or erosion of brief foul odor. Often it is difficult to differentiate this duration and is not very impressive. Most physicians disorder from syphilis, and unfortunately the avail­ have never seen one and probably never will because able laboratory tests for chancroid are not satisfac­ it is small and often overlooked by the patient. Soon tory. Occasional patients will have fairly clean-based after the primary phase in the male, large, tender lesions unlike the typical lesions of chancroid, but if lymph nodes appear. These are referred to as buboes. these lesions are multiple, there is less chance of In the female, lymphatic drainage is partially to the primary syphilis which usuallyis solitary. Tenderness perianal area, and therefore proctitis may occur as also suggests chancroid, but one cannot be sure with­ well as resultant stricture. The lymph nodes are usu­ out ruling out syphilis by means of a negative dark ally large, fluctuant, and tender. They may be unila- CARAVATI: CUTANEOUS MANIFESTATIONS OF VENERl'AL DISEASE 31 teral or bilateral. and both the inguinal and femoral physician's office. and only simple small erosions are nodes may be involved. seen. Then the physician has to depend on the history Granuloma inguinale, on the other hand. does that vesicles have occurred previously. not primarily involve the lymphatics. It is basically a One final point: there has been an increasing disease of large slowly growing ulcers which have a amount of evidence in recent years that there may be beefy red appearance.• and there is not usually lym­ some relationship between carcinoma of the cervix phatic involvement unless secondary bacterial in­ and herpesvirus type 2. This was initially discovered fection with other organisms supervenes. These le­ by cytological exams of individuals who had both sions may be markedly destructive. The beefy red. premalignant and malignant lesions of the cervix. granulomatous appearance is typical as is partial des­ These exams were noted to have the cytological ap­ truction of the genitalia. pearance typical of herpes infections, and there is also It should be noted that occasionally individuals an increased number of these patients who have more with one venereal disease may have another. l t is not antibodies to herpesvirus type 2 than do control rare to see a patient with gonorrhea and syphilis at groups.• The significance of these findings is not the same time. and any combination of these disorders clear. but some workers now feel that at least women is a possibility. Consequently. appropriate investiga­ with this type of infection should have more frequent tion should be done to rule out such simultaneous pap smears. maybe one every six months. occurrences. Finally, there is another problem which is in­ REFERENCES creasing rapidly in numbers of cases. This problem is I. Toda_r's VD control proble111. American Social Health Associa­ genital infections with herpesvirus. This is almost tion. New York. 1974. always with herpesvirus type 2, although occasionally type I will become involved." The lesions most fre­ 2. Cos

PEYTON E. WEARY. M.D.

Professor of Dermatology. University of Virginia School of Medicine. Charlouesville. Virginia

Skin cancer i, the most frequent type or cancer. atyrical. The so-called superlicial basal cell carci­ accounting r,ir about 20"; or all cancer, in the Stale noma orten looks ,·ery much like an eczematous of Yir1!inia. and the most common type or skin cancer proces,. One could easily mistake such a lt'sion for is the �basal cell carcinoma. The basal cell carcinoma psoriasis or nummular ecLema. Ho"·e1·er. at the edge is a tumor «hich is not considered highly malignant of such a lesion one "·ill see the s111all thread-like. hecause. in general. it does not melastasi1e. although pearly or "·axy border. Boll'en·s disease also may there have been a few instances in ll'hich metastases look ven· mud1 like superlicial basal cell carcino111a. have occurred. However. such lesions may be quite but it is. in !'act. an in situ squamous cell carcinoma. destructive al times. The typical basal cell carcinoma A nother atypical type or basal cell carcinoma is the presents as a waxy. rapular or nodular lesion which morphea-like or sclerosing basal cell carcinoma. As has a gelatinous or somewhat translucent arrear­ the tu111or extends al tho.: periphery. scarring 11·ill take ance. Coursing across the surface from the normal place in tho.: ccntcr. and the center of the lesion will skin toward the center of the lesion. one will orten see actual ii· disappear and be replaced by scar tissue. It is line telangiectatic vessels. At times the lesions may be often 1101 rccogniLed that basal cell carcinomas may somewhat decertive because of their location. and h;1vc a considerable amount of' pigment. The pig­ this is rarticularly true in the inner canthus "·here mented basal cell carcinoma 111a1· be ver\· diliicult to they may be missed until they are fairly large. Some dilkrcntiatc from a malignant melanoma because it basal cell carcinomas will remain relatively quiescent has many ,ir the characteristics that ll't' associate ll'ith l'or long reriods of time: others will become much malignant melanoma. such as rseudopods or pig­ more aggressive and grow raridly. The tumor may. at ment. times. be much like an iceberg with only the tir At times \\·e sec individuals ll'ho have a very appearing. and this is particularly a rroblem with extcnsi1·c process in which many hundreds or basal lesions on the nose. In treating a lesion in this loca­ cell carcinomas may occur. starting oftentimes in tion one has to be very cautious and be rrerared to childhood. and continuing "·ith development or new rcrl'orm gral'ting, if this is required. It may. at times. lesions. into adult life. Most or these individuals do be dillicult to differentiate a basal cell carcinoma nut survivc to late adult Iii"..: because of the scverity of from small lesions which we call sebaceous ade­ this process. In addition to the presence of these basal nornas. which occur frequently on the faces of elderly ccll carcinomas. th..:re are other features which allow individuals. These are small waxy. creamy elevations us to make a diagnosis ,if the nevoid basal cell carci­ usually on the forehead and they are the result of noma syndromc. Individuals ll'ith this condition have hyperplasia of sebaceous follicles. frontal bossing. lantern ja"·· and appear grotesque. Basal cell carcinomas are occasionally quite Thcy may have jaw cysts. abrwrmalities of the ribs Presented hy Dr. Wc�,r� al the.: -l7th Annual Mi.:Guirc Lc1:turc such as bilid ribs. and small pits ,in the palms and Series. 17 01:tnhcr. 1975. at thc Medical Cnlkgc: nf Virginia, soles. R ichrnund. Trcatment or basal cell carcinoma is quite var-

32 MCV ()LIAR'[ LRl.Y lc[I ): .1c-.1<. 1976 WEARY: MANAGEMENT OF CUTANEOUS MALIGNANCY 33 ied. Lesions can be excised .surgically. are ame­ amount of recurrence is no more than one would nable to x-ray therapy, and may be adequately expect to see with the other more conventional mod­ treated by electro-desiccation and curettage. The rec­ alities. ommended way to use this latter modality is to desic­ Epidermoid or squamous cell carcinoma is the cate the lesion, curette it and then repeat the same second most common type of skin cancer. Most such procedure with a final light desiccation to control lesions arise from sun-damaged skin. The association bleeding. If this is done properly, the cure rate should of squamous cell carcinoma and actinic exposure is approach 95% to 98%, and this is as good as one can very well appreciated, and we think that the actinic get with any form of management. Many dermatol­ keratosis or cutaneous horn is oftentimes a precursor. ogists now are turning to the use of cryosurgery. Squamous cell carcinoma arising from actinic kera­ liquid nitrogen in particular. for treatment of basal toses is a much less aggressive tumor than other types cell carcinomas. One may use a large cryotherapy of squamous cell carcinoma, often remaining well unit with either a probe or spray. and the recom­ confined to a localized area for a long period of time, mended treatment is to insert thermocouples beneath being slow to metastasize and quite amenable to the skin at approximately the base of the tumor. The treatment by cryosurgery. electro-desiccation, sur­ lesion should then be frozen to the point where the gery. or radiation therapy. Surgery is probably the temperature registered by the thermocouples is - 20 best-accepted treatment for such lesions. When C, and this temperature should be maintained for squamous cell carcinoma arises in pre-existing der­ approximately one to two minutes with a very slow matoses, long-standing ulcers. burn scars or sites of thaw. With this type of approach, the cure rate old radiation dermatitis. which is not a rare sequence should be very high. of events. the lesion is much more aggressive. more For the last four years I have been treating the apt to be anaplastic. metastasize early, and has to be majority of basal cell carcinomas with a method treated. therefore. in a much more aggressive fashion. which combines cryo- and chemotherapy. It is known If one encounters an area of chronic ulceration that topical 5-fluorouracil has significant destructive (stasis. decubitus. burn) which does not show signs of effects on various cutaneous tumors. Unfortunately. healing. it is very important to consider a biopsy to be application of 5-fluorouracil alone to a basal cell sure that one is not dealing with such a tumor. carcinoma has been ineffective, probably because the Bowen's disease. a form of in situ squamous cell surface epithelium overlying the tumor is intact. My carcinoma, is a disorder which may be very slow to rationale is to combine cryotherapy with subsequent change and it may be present for many months or application of 5-fluorouracilso that one destroys the years without undergoing rapid enlargement or with­ overlying epidermis and a portion of the tumor, out becoming an invasive carcinoma. Most of these thereby allowing the 5-fluorouracil to penetrate into lesions will probably become invasive if they are al­ the depths of the lesion and destroy any pseudopods lowed to remain in place indefinitely. Lesions of this of tumor which might persist. With this approach one sort are very amenable to treatment with cryotherapy can apply the liquid nitrogen on a cotton-tipped ap­ and topical 5-fluorouracil. or in some instances. the plicator stick to the lesion for a period of perhaps one use of topical 5-fluorouracil alone. They should be to two minutes. While the lesion is frozen. we take a biopsied and followed carefully to be sure that all of small curette and simply scoop out a small portion of the lesion is removed. the tumor for histologic verification (no local anes­ There is a condition we call keratoacanthoma thesia is needed). Bleeding afterwards can be con­ which looks clinically very much like squamous cell trolled by application of aluminum chloride. The carcinoma. Microscopically. as well. it may be some­ patient commences that evening, and twice a day what difficult for the histopathologist to differentiate thereafter, application of topical 5-fluorouracilin the such lesions from squamous cell carcinoma unless he form of 5% Efudexr"' ointment to the lesion. I usually has the entire specimen or very adequate specimen. have the patient cover the site with an occlusive The one feature about keratoacanthoma which is so Blenderm6• tape dressing. Treatment is continued for distinctive is its rapid growth. A lesion may attain a a period of two to three weeks, depending upon the size of I to 2 cm in a period of three to four weeks. depth and size of the lesion. With this treatment I Characteristically, the lesion exhibits a heaped-up or have treated perhaps 400 to 500 such lesions in the rounded border with a central horny plug. Occasion­ last four years. The cosmetic result is superb and the ally, one will see multiple lesions of keratoacan- 34 WEARY: MANAGEMENT OF CUTANEOUS MALIGNANCY thoma. Keratoacanthoma is called a benign, self­ between 20 and 40 pigmented lesions on the skin so it healing epithelioma and it is true that most such is a total impossibility to remove all such lesions. lesions, if left alone, will heal spontaneously. Unfor­ Some textbooks state that all pigmented lesions on tunately, the scar that results when they heal sponta­ the hands, the feet, and genitalia should be removed. neously is often not a satisfactory one and a more This is due to the fact that lesions in this location are suitable cosmetic result is obtained if these are ex­ largely junctional in nature, and we know that malig­ cised or treated with one or another modality. In nant melanoma arises most often from junctional addition, there have been a few instances in which lesions. It is now known that one out of five individ­ keratoacanthoma seems to have progressed to the uals has a pigmented lesion on the hands, feet, and development of squamous cell carcinoma, and even genitalia and. therefore, in order to prevent one ma­ occasionally into a metastatic squamous cell carci­ lignant melanoma, one would have to remove 10,000. noma. Keratoacanthomas are usually treated by ex­ such lesions: obviously an impracticality. On areas of cision. They can also be treated by electro-desiccation the hands and feet subjected to significant degrees of and curettage, but unfortunately, with such treat­ pressure or friction, pigmented lesions probably de­ ment, one does not have an adequate specimen. I now serve removal. We have all heard the statement that freeze such lesions with liquid nitrogen and, while moles that are on areas subject to friction from cloth­ they are frozen, shave-excise a major portion of the ing should be removed. There is very little really good lesion for a pathologic specimen. I then have the evidence to substantiate this concept. In order to patient apply topical 5-fluorouracil and an occlusive establish any real association, one would have to do a dressing as with a basal cell carcinoma. The end comprehensive, prospective study to really determine cosmetic results are very good. whether rubbing from clothing is enough to cause About 2% to 3% of internal malignancies may lesions to become malignant. We do at times remove metastasize to the skin. Recognition of these lesions, such lesions if the patient shows an obvious concern, of course, may allow one to make an early diagnosis but I am not inclined to remove them simply because of an internal malignant process. Characteristically, I am worried about malignancy in general. metastatic carcinoma is stony hard to palpation Lesions which are dome-shaped. uniform in rather than doughy or rubbery like a sebaceous cyst color. lightly colored brown, tan or skin colored, with or lipoma. The color may be normal skin color or well defined edges, are usually benign. Variation in various shades of brown, pink. or red. At times these color is probably one of the most significant and lesions appear to be very vascular. When they occur important features which would cause us to be sus­ on the scalp, which is not an infrequent site, the hair picious of malignant melanoma. Small blackish areas overlying such lesions is lost. In general. the incidence occurring in a nevus which has been uniformly col­ of metastasis from an underlying malignancy paral­ ored previously, and particularly blue-black color­ lels the incidence of these tumors in the population. ation, is highly suspicious.Not all black coloration of In other words, the two most common tumors to a nevus will be due to dark discoloration in the metastasize to the skin are the two most common depths of the lesion, however, and many times dark tumors in the population-carcinoma of the breast in keratinous material may accumulate on the surface in females and carcinoma of the lung in the male. Me­ little crypts to form black plugs. Lesions which show tastasis to the skin of an internal tumor generally pseudopods of pigment at the edge, or the edges of takes place in relative proximity to the site of the which are irregular and indistinct, may be active le­ tumor. A pelvic tumor might, therefore, be expected sions and should definitely be removed. Lesions with to metastasize to the perineum, a carcinoma of the alternating color. perhaps even hypopigmentation al lung may metastasize to the chest wall. They may times, probably should be removed. metastasize either by the blood, along the lymphatic Lesions arising in the proximal nail fold which channels, by implantation at the time of surgery, or disperse pigment into the nail plate itself. producing by actual growth of the tumor in underlying tissues longitudinal pigmented bands, may indicate the pres­ out to the skin, presenting there as a nodule. ence or a pigmented nevus in the matrix of the nail. Malignant melanoma is the most malignant or Such lesions occurring in Caucasians should all be skin tumors and it is important to realize that removed, but pigmented bands in the nails of black 50% of malignant melanomas arise de novo rather individuals are common and usually benign. Pig­ than in pre-existing nevi. The average individual has mented lesions on mucus membranes or transitional WEARY: MANAGEMENT OF CUTANEOUS MALIGNANCY 35 mucosal surfaces should be removed because they not present. A biopsy should be done of the most have a high incidence of malignant alteration. Occa­ suspicious areas before one uses cryotherapy to con­ sionally. one will see a so-called bathing trunk nevus. firm the fact that one is not dealing with a malignant often quite large and hairy as well as pigmented. process. Malignant melanoma occurring prior to the age of Two other special lesions should be mentioned puberty is a very uncommon circumstance. but when in conclusion. The blue nevus because of its blue it occurs, a number of melanomas have arisen in such color may be mistaken for a melanoma. It occurs large nevi. Sometimes these bathing trunk nevi cover most often on the distal extremities and usually by 75% to 80% of the body surface, and it is very difficult the time the patient is seen he may have had it for to remove the entire lesion. but as much as can be many years. If a patient comes in with a lesion such as removed with suitable grafting should be accom­ this. of recent onset, we might be suspicious that it is plished as early in life as possible. a blue nevus. but because we cannot always be sure Lentigo maligna is a lesion which occurs mostly that it is not a malignant melanoma, we remove a in older individuals. frequently on the face. and char­ small number of benign blue nevi. Blue nevi may acteristically will be present for many years. very occasionally become malignant, but this is certainly slowly growing at the edge. oftentimes with a grayish an unusual circumstance. The halo nevus is essen­ or slate color. There may be a significant degree of tially a benign nevus about which a halo of depig­ pigment variability from one area to another. After a mentation arises usually in the process of autode­ period of many months or years the lesion may de­ struction of the nevus. Generally speaking, we do not velop very dark or jet-black areas or a small nodule. advocate removal of the lesions because we know When this happens, the lesion, which was previously that most of them will not become malignant. Occa­ benign, has crossed the border into the malignant sionally, malignant melanoma may have a surround­ category. It is important to recognize that the mela­ ing halo of depigmentation and thus each such lesion noma that arises in such lesions is a much less aggres­ should be carefully examined. If you do remove a sive type of melanoma than that which arises in the halo nevus. be sure to tell the pathologist that this is a average pigmented mole. It will metastasize first to lesion that you suspect of being a halo nevus. because the regional nodes and often fairly late in the course. microscopically such lesions have an intense in­ whereas malignant melanoma of the usual type may flammatory response around them, and the in­ bypass the regional nodes and metastasize early to experienced pathologist looking at such a lesion may distant sites. Lentigo maligna can be treated by misinterpret this as evidence for a melanoma. simple excision or by cryotherapy. if malignancy is A service to medical education from A. H. Robins: 'es�i. Excerpted from Volume 2 The A H Robins G I Series consists of six book . oft lets. designed 10 provide a quick ye1 comprehen he s1ve review of basic procedures and practices 1n G G I medicine with particular emphasis on the . I physical examination as performed 1n the oll1ce or . . at bedside If you have teaching respons1b1ht1es t1m1ted quantities are available Pan 1 /nspecr,on Part 2 Palpation Part 3 Percuss,on. Part 4 Ausculta/lon. Part 5 Series Abdominal Pam and Part 6 Dtfferent,al Q,a9nos1s of Abdommal on physical examination Disorders Wnte 10 The Medical Department A H Robins Company 1407 Cummings Dnve. Richmond V1rq1n1a 23220 of the abdomen Normally palpable organs: the edge of the liver descending, on 1nspirat1on. below the costal margin (AJ: the lower pole of the right kidney (BJ; the abdominal aorta (CJ: the descending colon and the sigmoid (DJ, the ascend­ ing colon (E); and occasionally the bladder (though rising of this organ beyond the pubis does not necessarily 1nd1cate disease)

Impossible to outline unless diseased. distended or enlarged the gallbladder. pancreas. stomach. small 1ntest1ne. trans· verse colon and spleen A service to medical education from A. H. Robins: ,,es �- - Excerpted from Volume 2 i i i i of the The A H Rob ns G I Ser es conssts of sx book lets. designed 10 provide a quick. yet comprehen ti.· G. s1ve rev1ew of bas1c procedures and practices 1n I. G I medicine with particular emphasis on the phys1calexam1na11on as performed 1n the office or at bedside If you hc1ve teaching respons1b1l111es,Inspection S limited quant1t1esPalpation. are availablePercuss,on. Part 1 Auscultation erles Abdominal Pa,n D1flerent1al of Abdornmal Part 2 Part 3 Part 4 Pan 5 on physical examination Disorders and Part 6 o,aqnos,s of the abdomen. Wnle 10 The Medical Department AH Robins Company 1407 Cummings Dnve. Richmond V1rq1rna 23220 Normally palpable organs: the edge of the liver descending, on insp1rat1on. below the costal margin (AJ. the lower pole of the nghl kidney (BJ; lhe abdominal aorta (CJ, the descending colon and the sigmoid (DJ; lhe ascend­ ing colon (EJ; and occasionally the bladder (though rising of this organ beyond lhe pubis does not necessarily 1nd1ca1e disease) I mposs1ble 10 outline. unless • diseased, distended or enlarged each tablet. Briel summary. Adverse Reactions. Blurring of v1s1on. dry mouth. the gallbladder. pancreas. capsule or 5 cc te rrlul each d1ff1cull urination. and flushing or dryness of the skin may occur stomach. small intestine. trans­ a6fe� Don natal each on higher dosage levels, rarely on usual dosage. Contraind1ca- 1 verse colon and spleen (23% alcohol) No 2 Extenlab 1tons Glaucoma; renal or hepatic disease, obstructive uropathy am1ne sullale O 1037 mg O 1037 mg 0311 t mg (for example, bladder neck obslruct10A due to pros1at1c hyper­ ,esulfate 0.0194 mg 00194 mg 0.0582 mg trophy]; or hypersens1t1v11y lo any of the ingredients. ne hydrobromide 0.0065 mg 0 006S mg. 0 0195 mg A·H· OBINS Vir oarb1tal (Y,, gr.) 16 2 mg (\1!gr)324 mg (:Y. gr) 48 6 mg 1g may be habit forming) AH Rob1nsCompany.R1chmond. g1n1a23220 each tablet. Brief summary. Adverse Reactions· Blurring of vision. dry mouth. capsule or 5 cc d1fflcult urination. and flushing or dryness of the skin may occur tea;f fxrrful each e Donna1al each on higher dosage levels. rarely on usual dosage. Contraindica­ [23% alcohol] No 2 Extentab tions: Glaucoma; renal or hepatic disease. obstructive uropathy 1am1ne sulfate O 1 037 mg 0 1037 mg 03111 mg (for example. bladder neck obstruclloA due to prostat1c hyper­ 1esulfate 0.0194 mg 0.0194 mg 00582 mg trophy); or liypersens1t1v1ty to any of the ingredients. ne hydrobrom1de O 0065 mg 0 00 65mg 00195mg oarb1tal (V,i gr.) 16.2 mg (¥.>gr)324mg (% gr.)48 6 mg 1g may be habll forming) A·H·RO BINS A H Robins Company. Richmond. Virginia 23220