Lecture 7 - Vesiculobullous lesions II.pdf

DENT4008 ORAL MEDICINE 7. Vesiculobullous Lesions II Assist. Prof. Elif ÇELEBİ School of Dental Medicine Department of Oral and Maxillofacial Radiology [email protected] LEARNING OUTCOMES • Enlist various diseases that can manifest as vesicular and bullous lesions • Discuss the etiopath...

DENT4008 ORAL MEDICINE 7. Vesiculobullous Lesions II Assist. Prof. Elif ÇELEBİ School of Dental Medicine Department of Oral and Maxillofacial Radiology [email protected] LEARNING OUTCOMES • Enlist various diseases that can manifest as vesicular and bullous lesions • Discuss the etiopathogenesis, clinical features, investigations, differential diagnosis and management of vesiculobullous lesions of the oral cavity OUTLINE 1. Viral Herpes simplex Varicella Zoster Hand Foot Mouth Disease Herpangina Rubella (measles) 2. Immunological diseases Pemphigus Vulgaris Mucous Membrane Pemphigoid Bullous Pemphigoid Dermatitis Herpetiformis Linear Immunoglobulin A Disease 3. Hereditary Diseases Epidermolysis bullosa Dermatitis Herpetiformis Dermatitis herpetiformis is a chronic autoimmune dermatosis associated with a gluten-sensitive enteropathy. Patients with gluten-sensitive enteropathy develop dermatitis herpetiformis in approximately 15 to 25% of the cases. Cutaneous vesiculopapular disease characterized by intense pruritus. The disease is associated with granular IgA deposits in the papillary dermis Clinical features The disease occurs at any age, but is more common between ages 15 and 50, Males are more frequently affected than females with a ratio of 2:1 Lesions are usually symmetric in their distribution over the extensor surfaces, especially the elbows, shoulders, sacrum, and buttocks. Of diagnostic significance is the frequent involvement of the scalp and face. The oral mucosa can be involved in approximately 5 to 10% of the cases. Clinical features Cutaneous lesions are papular, erythematous, vesicular, and often intensely pruritic. Lesions are usually symmetric in their distribution over the extensor surfaces, especially the elbows, shoulders, sacrum, and buttocks. Of diagnostic significance is the frequent involvement of the scalp and face. Lesions usually are aggregated (herpetiform), but often are individually disposed. Oral lesions follow the skin eruption. Lesions may involve both keratinized and nonkeratinized mucosa Erythema, maculopapular lesions, and vesicles are observed in a centrifugal or hemicircular pattern. The vesicles rupture leaving superficial painful erosions resembling small aphthous ulcers. The most frequently affected sites are the palate, tongue, and buccal mucosa and more rarely the gingiva, lips, and tonsils Histopathology and immunopathology Dermatitis herpetiformis is characterized by papillary neutrophilic microabscesses and subepithelial vesicle formation. When an intact vesicle is biopsied, a subepidermal/subepithelial blister containing predominantly neutrophils are seen. Direct immunofluorescence reveals granular IgA deposits in the dermal papillae of perilesional skin. Treatment Dermatitis herpetiformis generally is treated with dapsone, sulfoxone, and sulfapyridine. Because patients often have an associated enteropathy, a gluten-free diet may also be part of the therapeutic regimen. Linear Immunoglobulin A Disease (LAD) LAD is a rare acquired subepithelial autoimmune blistering disease characterized by the deposition of predominantly IgA in the basement membrane. LAD occurs in children below the age of 10 (historically referred to as chronic bullous disease of childhood) and adults older than 60. The clinical manifestations may resemble MMP, BP, and EBA. Etiology and Pathogenesis The cause of the majority of cases is unknown, but some reported cases have been; drug‐induced (e.g., vancomycin, anti-inflammatory agents) amiodarone and nonsteroidal systemic diseases, including hematologic malignancies, ulcerative colitis, or connective tissue diseases, such as dermatomyositis. Clinical Manifestations ‐ General The skin lesions of LAD are characterized by annular pruritic papules and blisters, giving a “cluster of jewels” appearance. Oral Findings Oral lesions are common in LAD and may be seen in up to 70% of patients. These lesions are clinically indistinguishable from the oral lesions of MMP, with blisters and erosions of the mucosa frequently accompanied by desquamative gingivitis Linear immunoglobulin (Ig)A disease showing subepithelial separation with neutrophils and eosinophils. Histologically, separation at the basement membrane zone (subepithelial separation similar to MMP) is seen. Neutrophils and eosinophils often fill the separation. With DIF, linear deposits of IgA are found at the epithelium–connective tissue interface. Management The majority of patients will have a disease triggered by a drug and therefore identification is key. As in MMP, topical corticosteroids may be helpful. More severe cases may require a combination of systemic corticosteroids and immunosuppressive drug therapy. Epidermolysis bullosa Epidermolysis bullosa is a general term of diseases that are characterized by the formation of blisters at sites of minor trauma. Encompasses one acquired and many genetic or hereditary varieties In hereditary forms of epidermolysis bullosa, pathogenesis appears to be related to genetic defects in basal cells, hemidesmosomes, or anchoring connective tissue filaments, depending on the disease subtype. Epidermolysis bullosa The acquired nonhereditary autoimmune form, known as epidermolysis bullosa acquisita, often is precipitated by exposure to specific drugs. In this type, IgG deposits are commonly found in sub–basement membrane tissue and type VII collagen (the main constituent of anchoring fibrils) antibodies located below the lamina densa of the basement membrane. Clinical features Bulla formation from minor trauma, usually over areas of stress such as the elbows and the knees. Onset of disease is seen during infancy or early childhood for the hereditary forms, and during adulthood for the acquired type. Blisters may be widespread and severe and may result in scarring and atrophy. Nails may be dystrophic in some forms of this disease. Oral lesions are particularly common and severe in the recessive forms of this group of diseases and uncommon in the acquired form. Oral manifestations include; 1. Bullae that heal with scar formation, 2. A constricted oral orifice resulting from scar contracture, 3. Hypoplastic teeth. Epidermolysis bullosa in a child. Note ulcers, constricted opening, and atrophic tongue mucosa. Treatment Therapy includes avoidance of trauma, supportive measures, and chemotherapeutic agents (none of which is consistently effective). Corticosteroids, vitamin E, phenytoin, retinoids, dapsone, and immunosuppressive agents all have been suggested as providing some benefit to patients. Erythema Multiforme Erythema multiforme (EM) is an acute self-limiting hypersensitivity reaction characterized by target skin lesions and/or ulcerative oral lesions. The Etiology of EM is unknown, although a hypersensitivity reaction is suspected like infections and drugs. It has been divided into two subtypes: Minor form, usually associated with an HSV trigger Major severe form, triggered by certain systemic drugs. Clinical features EM is usually an acute, self-limited process that affects the skin or mucous membranes or both. Between 25% and 50% of patients have oral manifestations. It may on occasion be chronic, or it may be a recurring acute problem. In recurrent disease, prodromal symptoms may be experienced before any eruption. Young adults are most commonly affected. Clinical features The term erythema multiforme indicates the multiple and varied clinical appearances that are associated with cutaneous manifestations of this disease. The classic skin lesion of EM is the target or iris lesion. Typically, the extremities are involved, usually in a symmetric distribution. Other types of skin manifestations of EM include macules, papules, vesicles, bullae, and urticarial plaques. Erythema multiforme cutaneous target lesions. It consists of concentric erythematous rings separated by rings of near-normal color. Within the mouth, EM characteristically presents as an ulcerative disease Short-lived vesicles or bullae are infrequently seen at initial presentation. Lips, buccal mucosa, palate, and tongue Recurrent oral lesions may appear as multiple painful ulcers Histopathology The microscopic pattern of EM varies but consists of epithelial hyperplasia and spongiosis. Basal and parabasal apoptotic keratinocytes are usually seen. Vesicles occur at the epithelium–connective tissue interface, although intraepithelial vesiculation may be seen. Epithelial necrosis is a frequent finding. Treatment In EM minor, symptomatic treatment, including keeping the mouth clean with bland mouth rinses, may be all that is necessary. In EM major, topical corticosteroids with antifungals may help control disease. The use of systemic corticosteroids remains controversial and is believed by some to be contraindicated, particularly as maintenance therapy. Acyclovir may be effective in preventing recurrences in patients who have an HSV-triggered disease. Supportive measures, such as oral irrigation, adequate fluid intake, and use of antipyretics, may provide patients with substantial benefit. Stevens‐Johnson Syndrome Stevens-Johnson syndrome is a relatively rare, acute, life-threatening mucocutaneous disease of an immune complex– mediated hypersensitivity, which is nearly always drug-related. Prodromal symptoms include fever, cough, fatigue, malaise, sore throat, arthralgia, myalgias, diarrhea, photophobia, etc. usually precede by 1 to 3 days the development of mucosal and skin manifestations. Clinical features The oral mucosa is almost always involved, with extensive formation of vesicles or bullae that rupture quickly to leave extensive and painful erosions that are covered by grayis-white or hemorrhagic pseudomembranes/crusts. Clinical features The lesions usually extend to the pharynx, larynx, esophagus, and respiratory system. The ocular lesions follow in frequency and consist of severe conjunctivitis. Pathology Histopathologic examination of skin biopsy is useful for confirming the diagnosis. It reveals subepidermal bullae with epidermal cell necrosis. Treatment Early diagnosis, cessation of the causative drug, and rapid start of supportive and specific treatment are recommended. References Jean M. Bruch; Nathaniel Treister. Clinical Oral Medicine and Pathology: Springer. 2016. Joseph Regezi, James Sciubba, Richard Jordan. Oral Pathology Clinical Pathologic Correlations. 7th Edition. Saunders; 2016 George Laskaris. Color Atlas of Oral Diseases: Diagnosis and Treatment. Thieme Medical Publishers; 4th editon Edward W Odell. Cawson's Essentials of Oral Pathology and Oral Medicine E-Book (9th ed.). Elsevier Health Sciences; May 2017