White : Diseases of the Skin - Oral and Genital Disorders

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Gary M. White & Neil H. Cox

Diseases of the Skin

20	Oral and Genital Disorders

ORAL MUCOSA

See also lupus erythematosus (Ch.13), cicatricial pemphigoid (Ch.16), and lichen planus (Ch. 8).

Aphthous ulcers

Etiology and pathogenesis

Aphthous ulcers are a common cause of painful ulcers of the mouth. In women, they may correlate with the menstrual cycle. Extensive and painful aphthosis may occur in patients with HIV. The majority of cases are idiopathic. Some have suggested that recurrent aphthous stomatitis may have an immunogenetic background owing to cross-reactivity with Streptococcus sanguis . A small percentage of patients have a hematinic deficiency (e.g. iron, folate, or vitamin B12). Case reports of isolated causes include zinc deficiency and fluoride allergy.

Clinical

Several clinical variants are described.

•	Minor aphthous ulcers. These are the most common; the lesions appear as 3–10-mm diameter, grayish white ulcers with a red margin (Fig.20.1). They are usually quite tender and may occur in crops.
•	Major aphthous ulcers—these are larger, more painful, and recurrent.
•	Herpetiform ulceration (Fig. 20.2)—this is extremely painful and recurs quite frequently. The lesions appear as tiny (2mm) vesicles that rapidly ulcerate and may coalesce to form a ragged ulcer. There is no relation to herpes simplex infection.

Figure 20.1 Aphthous ulcers. A gray-white oval ulcer with a bright-red margin is typical. These lesions are usually quite painful.

Figure 20.2 Herpetiform mouth ulcers. This patient had lost 10 kg because of inability to eat. He gained 4 kg within a month of starting tetracycline.

Differential diagnosis

See Table 20.1.

Treatment

No treatment is necessary for minor and transient lesions. For more severe disease, amlexanox is US Food and Drug Administration-approved for
the treatment of recurrent aphthous ulcers. Alternatively, sucralfate (an aluminum salt of sucrose octasulfate) suspension has been used successfully in patients with Behçet disease and aphthous stomatitis. It may be applied intraorally to each lesion up to four times per day. Routine use of a hypoallergenic toothpaste is helpful in some patients. If more therapy is needed, a high-potency topical steroid three to four times a day may be tried.

For patients who resist these interventions, colchicine (1.5mg/day) prophylactically may be administered. Other reported treatments include topical tetracycline (e.g. oral suspension held in the mouth for 2min and swallowed, four times a day), thalidomide, and 5-acetylsalicylic acid cream. Finally, systemic steroids are an extreme intervention but have also been shown to work well in adults.

For herpetiform mouth ulcers, oral tetracycline is effective.

Behçet disease

Etiology and pathogenesis

Behçet disease (BD; see also Ch.14) is an inflammatory condition that classically presents with both oral and genital ulcers. Since the original description, it has been recognized as being able to affect many organ systems, including the eye (e.g. relapsing iridocyclitis), central nervous system (e.g. meningoencephalitis), joints, and skin (e.g. erythema nodosum-like, vasculitic, or papulopustular lesions). The heart and lungs may rarely be affected. Its cause is unknown, but many consider it an autoimmune disease that may be triggered by infectious antigens. Geographic areas of high incidence include Japan, the Mediterranean, and countries of the Middle East.

Clinical

The lesions of BD begin as small erythematous or pustular lesions, which erode to form painful ulcerations. Lesions in men are usually painful, but the pain experienced by women is variable. The diagnosis is usually made clinically by the presence of oral aphthae (Fig.20.3) and at least two of the following: genital aphthae (Fig.20.4), posterior uveitis, pustular vasculitis (Fig.20.5), and arthritis. One characteristic clinical finding that is sometimes used to support the diagnosis is that of pathergy (a typical lesion occurring at the site of trauma). Pathergy may be elicited by oblique sterile insertion of a 20-gauge or smaller needle in normal skin. Look for a pustule 4–48h later. Recurrent oral ulcerations may pre-date the full syndrome by months to years (a 7.7-year average was found in one study of 67 patients presenting with recurrent oral ulcerations).

Figure 20.3 Oral ulcerations in Behçet disease.

Table 20.1 DIFFERENTIAL DIAGNOSIS OF ORAL ULCERS

Process	Examples	Comments
Aphthous ulcers	Minor, major, and herpetiform patterns	Note also that numerous medications and other ingested chemicals have been implicated as a cause of aphthae
Bullous diseases	Especially pemphigus vulgaris and other autoimmune bullous diseases; also ruptured lesions of angina bullosa hemorrhagica	Usually large erosions in pemphigus desquamative gingivitis
Other autoimmune diseases	For example lichen planus, lupus erythematosus	Oral lichen planus is discussed in Chapter 8
Viral infections	For example herpangina, herpetic gingivostomatitis	Especially in children
Other infections	Secondary syphilis, mucous patches	Classically have a ‘snail track’ pattern
Vasculitides and neutrophilic dermatoses	Behçet disease Wegener granulomatosis Pyoderma gangrenosum	A prerequisite for diagnosis of Behçet disease Wegener granulomatosis usually involves nasal mucosa A rare pattern of pyoderma gangrenosum
Allergic contact dermatitis	For example to dental amalgam	Causes oral lichenoid eruption, see Chapter 8
Physical	Bitten cheek, trauma from rough dental ?llings, etc.	Occasionally occurs as a form of dermatitis artefacta
Others	Cyclic neutropenia	Recurrent aphthous-type ulcers every few weeks

Figure 20.4 Non-oral manifestations of Behçet disease (a,b) Genital ulceration may be multiple or solitary, and may occur as the first manifestation of Behçet disease or in established cases. Infective causes of genital ulceration must be excluded. (c) A pustular vasculitis may also occur; this image is actually a pustular vasculitis secondary to ulcerative colitis but the clinical morphology is similar to that seen in Behçet disease.

Figure 20.5 Vasculitic lesions on the ear in a patient with Behçet disease.

Figure 20.6 Mucous patches of secondary syphilis. Round or oval white plaques may occur on the tongue in secondary syphilis.

Differential diagnosis

See Table 20.1.

Treatment

Minor forms of BD may be treated with a potent topical steroid. More severe cases may need systemic therapy. A variety of agents have been used. Infliximab infusion can be incredibly effective in healing both oral–genital and ocular manifestations. Prednisone (1mg/kg per day) and azathioprine (100–200mg/day) have been used. Ciclosporin has been reported very effective in treating both ocular and cutaneous manifestations. Interferon-alpha-2a also appears to be quite effective. The following have also been employed: dapsone (100–200mg/day), methotrexate (15g/week), colchicine (0.6mg three times a day), intralesional or topical steroids, pentoxifylline, and thalidomide.

Secondary syphilis

A variety of changes may occur in the mouth of patients with secondary syphilis (Figs 20.6 and 20.7). For example, whitish grey papules and plaques may occur on the tongue or other mucosal surfaces. Shallow erosions may occur as well. See Sexually transmitted diseases section later in this chapter for a further discussion of secondary syphilis.

Figure 20.7 Ulceration of secondary syphilis. Ulcerations may occur on the lips in the later stages of secondary syphilis.

Figure 20.8 Pemphigus vulgaris. This patient presented with oral ulcerations only. The differential included Behçet disease and severe aphthosis.

Pemphigus vulgaris

Etiology and pathogenesis

See Chapter 16.

Clinical

Oral erosions commonly occur in the patient with pemphigus vulgaris, and indeed are the presenting complaint in up to 60% of patients (Fig.20.8). This may be because there is a large amount of the pemphigus antigen in the buccal mucosa, although more recent studies suggest that the predominant autoantibody determines the site involved (those with mucosal-only disease having anti-desmoglein (Dg)3 and those with skin and mucosal disease having anti-Dg1 and anti-Dg3; see Ch.16). The esophagus may be involved rarely, and sloughing of its entire surface has been reported. Eating may become difficult. Herpes simplex infection may coexist. Childhood cases may occur rarely.

Differential diagnosis

See Table 20.1. The main diagnostic problem is in those with mild disease, those with pemphigus vulgaris limited to the mouth without subsequent skin involvement, and those with a gingivitis pattern (mucous membrane pemphigoid and lichen planus may be difficult to distinguish clinically). Diagnosis may be aided by performing immunofluorescence tests or measuring antidesmoglein antibodies.

Figure 20.9 (a,b) Fibroma. This firm nodule may occur on the lip, buccal mucosa, or tongue. It is benign but may be quite bothersome to the patient.

Treatment

Mild cases may be treated with fluocinonide gel or clobetasol propionate ointment five times per day. Clobetasol propionate has a more rapid onset of action and achieves longer remissions. However, both predispose to the development of candidiasis. If the gums are involved, the above steroids can be held in place with a mouth guard (purchased at any sporting goods store) worn for 15–20 min daily or twice a day. Intralesional triamcinolone (10–20mg/mL) has been used. Mild to moderate disease may be treated initially with prednisone (20–60mg every other day); daily or higher dosing is needed if the disease is unresponsive. For recalcitrant disease, intravenous immunoglobulin should be considered. The patient should be encouraged to have regular dental examinations.

Fibroma

A firm, smooth papule or nodule on the buccal mucosa or tongue at a site of frequent trauma is characteristic (Fig.20.9). This irritation fibroma is a very common intraoral lesion. It may be removed by simple excision or shave excision.

Bite line

The teeth may compress the inner surface of the buccal mucosa, forming a ‘bite line'. This change is common and often asymptomatic (Fig. 20.10).

Figure 20.10 Bite line. The occlusive line where the upper and lower teeth meet can form a mark on the buccal mucosa.

Figure 20.11 Torus palatine.

Kaposi sarcoma

Kaposi sarcoma is common in the mouth of HIV-positive patients (see Fig.12.64).

Torus palatine

The torus palatine is a very common, hard, midline, palatal lesion that represents a bony exostosis. No treatment is needed (Fig. 20.11).

Angina bullosa hemorrhagica

The sudden appearance of a blood blister on the oral mucosa (Fig.20.12), most commonly at the junction of the hard and soft palate, is characteristic. This painful lesion typically develops suddenly, during or immediately after hard food is eaten but sometimes after drinking liquids. Most bullae rupture spontaneously, leaving a jagged erosion that heals.

The buccal mucosa or other intraoral sites may be affected. No treatment is needed. In one unusual case, acute upper airway obstruction was caused by a rapidly expanding blood-filled bulla in the oropharynx.

White sponge nevus

The white sponge nevus is analogous to a congenital epithelial nevus but on the oral mucosa. The labial or perianal mucosa may be affected as well. A clinically similar leukokeratosis may be seen in dyskeratosis congenita. Familial cases occur with autosomal dominant inheritance. In some cases, the cause is a genetic mutation. For example, cosegregation of the disease with the keratin gene cluster on chromosome 17 was found, as well as a mutation of the gene encoding keratin 13. A mutation of the gene that codes for keratin 4 was found in two families. White, hyperkeratotic, spongy, non-tender plaques of the oral mucosa, developing in childhood, are characteristic (Fig. 20.13). Usually, no treatment is needed or effective.

Figure 20.12 Angina bullosa hemorrhagica. This benign blood blister will resolve spontaneously.

Figure 20.13 White sponge nevus.

Pigmented macules of the oral mucosa

The following should be considered.

•	Laugier–Hunziker syndrome—discussed in the section on lips (later in this chapter). Look for pigmentation of the nails and fingertips as well. There are no associated abnormalities.
•	Peutz–Jeghers syndrome—onset is in infancy or childhood. Associated with gastrointestinal polyposis
•	Addison disease—a low cortisol and poor response to synacthen test confirms this diagnosis.