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.