COM July 2005 Diagnosis

Multiple Oral Ulcerations and Skin Rash

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This is a 48-year-old white female who presented to the University of Washington School of Dentistry DECOD Clinic complaining mainly of soreness under her upper partial denture, which was constructed three months prior to this episode.

1. Drug Reaction/Stevens-Johnson Syndrome

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Stevens Johnson Syndrome (SJS) Any drug, including over the counter drugs, can cause Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), both of which represent a severe form of erythema multiforme. SJS is a skin and mucous membrane disease that can cause rashes, bullae, ulcers and epithelial sloughing (skin peeling which is more common in TEN). It is an IgE immune-mediated hypersensitivity reaction most frequently caused by drug intake, especially sulfa drug, as is the case with our patient who used bacterim for a urinary tract infection. SJS may also be a sequel to viral or mycoplasma infections, and occasionally to an underling malignant neoplasm or a gastrointestinal disease. It affects both the skin and mucous membranes. Skin lesions are usually the first to appear followed by the mucous membrane blistering and ulcerations, although the reverse is also possible. They present with a rash on the extremities, progressing to the back, buttock, chest and other skin areas. The mucous membrane includes the mouth, eyes (may lead to blindness), genitalia, the gastrointestinal tract and the respiratory tract. The latter two are serious, especially if they lead to esophageal stricture and respiratory failure because of sever epithelial sloughing. In the oral cavity, SJS is more related to drug reaction, especially sulfa drugs. It presents as acute and chronic types with varying degrees of severity. It may be life-threatening, especially in children. The antibodies target the epithelium and the superficial blood vessels leading to epithelial ulceration, sloughing and vascular leakage. Clinically, it is most common in young males (2:1 M:F ratio) between ages 20-40. It may also affect children. Diagnosis is often made on the basis of the clinical presentation. Neither the hematoxyline and eosine histology nor the immunofluoresence stains are specific. Treatment includes the withdrawal of the causing drug if determined, fluids, supportive care, systemic steroids and immune suppressants dependent on severity (1-3). The bullae and ulcers may continue to appear even after the causative agent (bacterim in this case) is discontinued. It takes six to eight weeks for the epithelial lesions to heal. The prognosis is determined clinically on a scoring system known as SCORTEN (grades 1-5); the higher the number, the worse the prognosis. For example the mortality rate of grade 5 is over 90%.

Treatment

Use of Bacterim was discontinued and the patient was placed on simple time and symptomatic treatment with no need for systemic steroid treatment. She was, however, placed on triamcinolone cream applications for the skin rash.

References

  1. Ayangco L Dermatol Clin. 2003 Jan;21(1):195-205.
  2. Scully C. Practitioner. 2001 Nov;245(1628):942-4, 946, 949-52.
  3. Axell T. Acta Odontol Scand. 2001 Oct;59(5):315-9.
  4. Sapp P, Eversole LR. Contemporary Oral pathology. Second Edition, Mosby, 2004.
  5. Weedon D. Skin Pathology. Churchil-Livingston, 2001.
  6. Williams DM.Vesiculo-bullous diseases: J Oral Pathol Med. 1990 Jan;19(1):16-23.
  7. Burgess JA et al Drugs. 1990 Jan;39(1):54-65.
  8. Kaplan RP. Clin Dermatol. 1987 Jan-Mar;5(1):43-51.
  9. Robinson NA et al Aust Dent J. 2003 Dec;48(4):206-11.
  10. Edwards PC Oral lichen planus: J Can Dent Assoc. 2002 Sep;68(8):494-9.
  11. Sugerman PB The pathogenesis of oral lichen planus. Crit Rev Oral Biol Med. 2002; 13(4):350-65.
  12. Abdollahi M J Contemp Dent Pract. 2003 Feb 15;4(1):10-31.
  13. Stoopler ET N Y State Dent J. 2003 Oct;69(8):28-31.
  14. Boyd AS Lichen planus. J Am Acad Dermatol. 1991 Oct;25(4):593-619.

2. Pemphigus Vulgaris

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This is a chronic immune-mediated condition that causes sloughing of the epithelium of both skin and mucous membranes, including the mouth. The IgG and C3 antibodies target the intercellular desmosomal adhesion molecules called desmogleins. This results in the breakdown of the middle part of the spinous layer, leaving the basement membrane intact. This disease is less common in the oral cavity than the lichen plan, oral mucous membrane pemphigoid and erythema multiforme. It is, however, a serious and life-threatening disease if untreated. Patients with this condition also develop circulating antibodies with the titre, which reflects the severity of the local disease. Drugs such as penicillamine can induce PV. Neoplasms such as leukemia and lymphoma can induce paraneoplastic PV (4-5). The protein targeted in the latter type is known as desmoplakin. This disease has a high prevalence in patients of Mediterranean origin, such as Jews, Greeks, and Italians. Females are affected more commonly than males (2:1 F:M ratio). It occurs more in patients ages 40 to 60, and rarely in children. Oral lesions are not common. 50% of the time PV presents first in the oral cavity; in such cases the skin lesions appear within a few weeks to months after the oral lesions. Four types have been described; pemphigus vulgaris is the most common constituting 80% of all pemphigus cases. Skin lesions frequently present as vesicles and bullae. Breaking into ulcers and sloughing of the epithelium, the palate is a common area. Nikolsky sign is positive. A biopsy would demonstrate a supra-basilar clefting, leading to splitting of the epithelium above the basal cell layer. Epithelial cells undergo acantholysis. The immunofluoresence stain is positive with IgG and C3 complement demonstrating a chicken wire appearance of the intercellular area above the basal cell layer. It is usually treated with systemic steroids and immune suppressants depending on the severity (4-5). The rapid onset of this case is not compatible with pemphigus vulgaris which is a slow and progressive disease.

3. Mucous Membrane Pemphigoid

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This is a chronic autoimmune disease affecting predominantly mucous membrane and rarely the skin (bullous pemphigoid). The most commonly affected mucous membranes are the oral cavity and the eyes, the latter of which tends to scar. It may also affect the nose, oro and nasopharynx and the esophagus. The skin lesions are rare and in the form of single or multiple bullae affecting mostly the head and neck area. 85% affect the oral cavity, especially the gingiva. The immune system recognizes proteins BP-1 and 2, laminin in the hemidesmosomes along the basement membrane as foreign. It targets them with IgG and C3 antibodies forming complex attracting neutrophils and other inflammatory cells leading to sloughing of the epithelium via the clean separation of the surface epithelium from the connective tissue. Gingiva is the most commonly affected location presenting as thin, atrophic or with sloughing epithelium (desquamative gingivitis) therefore rendering the dentist as the first clinician to see these patients. If the gingival lesions are not treated, they will slowly and progressively involve other areas such as the tongue and the buccal mucosa. The gingiva loses its stippling. There may be sloughing and desquamation of the epithelium, especially to mechanical pressure (positive Nikolsky sign) such as from brushing and denture irritation. The oral mucous membrane pemphigoid (OMMP) is believed to be different from that of the eyes, in that it does not scar, while the lesions of the eyes usually heal with scarring and are thus referred to as cicatricial (scar forming) pemphigoid. The eye lesions may cause blindness. Patients with OMMP have circulating antibodies but the antibody titer does not reflect the severity of the disease, as is the case with pemphigus vulgaris. The most common age is over 40 years. However, it is also described in children, especially females. The biopsy shows a sub-basilar split of the intact surface epithelium from the underlying fibrous connective tissue. Many inflammatory cells, including eosinophils are present. Immunoflourescent staining is positive with IgG and C3 in form of a uniform line along the basement membrane. Treatment is usually systemic steroids and immune suppressants and is dependent on severity. Antibiotics are also used to prevent or treat secondary infections. While the oral lesions may be supportive of this diagnosis, the skin lesions are not.

4. Lichen Planus

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Lichen planus is a common skin and mucosal disease, affecting up to 3% of the population. It is a chronic disease that comes and goes over the years. It is an immune-mediated reaction by T-lymphocytes to epithelial cells, especially those of the basal cell layer. It can occur in the mouth alone, on the skin alone, or on both. Clinically, LP occurs in adults between 30 & 70 years of age with a strong female predilection. It is often associated with stressful life styles. 40% of cases patients have both oral and skin lesions. On the skin, the presentation is referred to as the 4 Ps (polychnal, pruritic, purplish, papules). The papules are covered by a white and keratotic surface. Skin lesions are usually itchy and oral lesions can be either asymptomatic or involve burning sensations and pain. On the skin, they most commonly present on the flexor surfaces of the wrist the trunk and the thighs, while in the mouth they present over 80% of the time as bilateral and symmetrical buccal mucosa and vestibule followed by the tongue. Oral LP are classified as reticular (most common), erosive (thin and ulcerated mucosa) and hyperplastic (plaque). The plaque type is difficult to distinguish from leukoplakia. Reticular LP is the most common type in the mouth and is easy to identify since it presents with thin lines interlacing against an erythematosus bluish background. The lines are known as the striae of Wickham. Reticular LP is usually asymptomatic but it can become symptomatic if it progresses to erosive LP. Erosive LP is the second most common type in the mouth. Patients usually complain of sensitivity to hot and cold food and beverages, spicy food and alcohol. Clinically, it is hard to distinguish it from candidiasis and other mucocutaneous diseases such as Mucous Membrane Pemphigoid and Pemphigus Vulgaris. The mucosa appears red, thin and ulcerated. At times, radiating white striae are present at the periphery of the lesions. Hyperplastic (plaque) LP is uncommon and presents as confluent white areas simulating Leukoplakia. The dorsal surface of the tongue is the most common location for this type. LP has a distinct and well-defined histology. The immunofluorescence features include positive fibrinogen along the basement membrane in over 80% of cases. Fibrinogen, however, is not a specific antibody. It is present in ulcerated and any irritated tissue as well. Lichenoid Drug Reaction is a common condition, especially in elderly patients and presents mostly in the mouth as an erosive LP with a central ulcer and white striae radiating at the periphery in a vertical manner to the ulcerated center. They are present mostly on the posterior buccal mucosa. They are associated with the ingestion of a number of medications such as antibiotics, antihypertensive drugs, allopurinol (gout), diuretics, antidiabetics, gold, mercury, antibiotics, and antihistamines. Treatment ranges from doing nothing to treating with topical steroids, e.g. betamethasone 0.1% cream, and rarely intralesional steroids. Systemic steroid therapy can be used if severe, such as in erosive LP. For lichenoid drug reaction, the best treatment is replacement of the causing medication with another one. Both skin and oral lesions can spontaneously heal, leaving a pigmented areas on the skin and sometimes in the mouth. Skin lesion can heals within a year or two while mouth lesions can last much longer, at times past five years. Neither the oral lesions nor the skin lesions in this case are supportive of a diagnosis of lichen planus.