Oral manifestations of connective tissue disease and novel therapeutic approaches.

Connective tissue diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren syndrome (SS) have presented many difficulties both in their diagnosis and treatment. Known causes for this difficulty include uncertainty of disease etiology, the multitude of clinical presentations, the unpredictable disease course, and the variable cell types, soluble mediators, and tissue factors that are believed to play a role in the pathogenesis of connective tissue diseases. The characteristic oral findings seen with these specific connective tissue diseases may assist with more swift diagnostic capability. Additionally, the recent use of biologics may redefine the success rate in the treatment and management of the disease. In this review we describe the oral manifestations associated with SLE, SSc, and SS and review the novel biologic drugs used to treat these conditions.

Dermatologic manifestations of zoonotic diseases transmitted by dogs: "Spot" could give you spots.

The bond between humans and dogs is precious and has been treasured since ancient times. Dog ownership is linked to numerous health benefits, such as increased physical activity and social functioning and decreased depression and cardiovascular events. However, dogs can transmit zoonotic diseases to humans, many of which present with cutaneous findings. This review summarizes the dermatologic manifestations, transmission routes, diagnosis, and treatment of zoonotic diseases transmitted by dogs, including vector-borne, bacterial, viral, fungal, and parasitic infections. This review emphasizes the significance of clinicians obtaining a comprehensive exposure history when patients exhibit a rash of unknown origin. Such an approach can provide valuable epidemiological clues related to diagnosing a zoonotic disease transmitted by a pet dog. Furthermore, identifying the dog as an infection source and subsequent veterinary treatment can help prevent recurrent infections in dermatologic patients.

Coexistence of oral lichen planus and vulvar lichen sclerosus.

OBJECTIVE: Oral lichen planus (OLP) is a mucosal variant of lichen planus. Lichen sclerosus (LS) is an inflammatory disorder with a predilection for genital skin. We aimed to identify the characteristics of patients with both mucosal diagnoses. STUDY DESIGN: This retrospective study included 86 women with both OLP and vulvar LS diagnosed from June 1, 1991 through November 30, 2020 at a Mayo Clinic campus in Rochester, Minnesota; Scottsdale, Arizona; or Jacksonville, Florida. Data included treatments, other cutaneous diagnoses, comorbidities, and information on patch testing and malignant transformation. RESULTS: The median patient age at diagnosis was 64.5 years for OLP and 65.6 years for vulvar LS. A diagnosis of OLP before vulvar LS was most common (50.0%). The most frequently used treatment for both conditions was topical corticosteroids. Oral squamous cell carcinoma (SCC) did not develop in any patient, but vulvar SCC developed in 2 (2.3%). CONCLUSIONS: OLP and vulvar LS may coexist, commonly beginning in the patient's seventh decade. Topical corticosteroids are often used to manage both conditions. The coexistence of both diseases did not seem to portend a greater malignancy risk.

Pemphigoid nodularis: a case report.

Several variants of bullous pemphigoid have been reported including pemphigoid nodularis. Patients with pemphigoid nodularis have clinical features of prurigo nodularis in combination with clinical or immunologic characteristics of bullous pemphigoid. We report the case of a 71-year-old woman with pemphigoid nodularis. The diagnosis was suspected clinically and established by positive indirect immunofluorescence (IIF) findings characteristic of pemphigoid. Results of direct immunofluorescence (DIF) testing were negative, which emphasizes the importance of conducting both DIF and IIF when pemphigoid nodularis is suspected.

Reactive nonsexually related acute genital ulcers: review of cases evaluated at Mayo Clinic.

BACKGROUND: Reactive nonsexually related acute genital ulcers (RNSRAGU) occur in pubertal girls after an acute systemic infection. OBJECTIVE: We sought to characterize RNSRAGU by reviewing the medical records of patients with this disorder. METHODS: We searched our medical index database from 1997 to 2007 for RNSRAGU cases. Questionnaires were mailed to identified patients. RESULTS: The study included 10 patients; 5 responded to the questionnaire. The mean age at onset was 11.5 years. Vulvar ulcers were preceded by viral gastroenteritis (n = 3), viral upper respiratory tract infection (n = 3), streptococcal pharyngitis (n = 1), influenza (n = 1), and other nonspecific febrile illnesses (n = 2). Seven patients had oral involvement also; 6 had at least one recurrence; and 3 were hospitalized for pain control. Analgesics and topical corticosteroids were the most common treatments. Ulcerations resolved within several weeks in all patients. LIMITATIONS: Retrospective study design, small study size, and 50% questionnaire response rate are limitations. CONCLUSIONS: Although rare, RNSRAGU should be considered when genital ulceration follows an acute systemic illness.

Ulcus vulvae acutum in a 13-year-old girl after influenza A infection.

A 13-year-old otherwise healthy premenarchal girl presented with acute onset of painful vulvar ulcerations. One day before developing vulvar ulcerations, she experienced flu-like symptoms, including a low-grade fever, cough, sore throat, and myalgia. Results of a throat swab were positive for influenza A infection (polymerase chain reaction [PCR] assay), and the patient was treated with oseltamivir. The patient's constitutional symptoms improved slightly, but within 2 days after her initial presentation, she returned to her primary care provider and described 24 hours of dysuria and vulvar swelling. She had a history of herpes labialis (cold sores) and rare episodes of minor oral aphthae (canker sores) that occurred less than twice a year. The patient denied a history of sexual activity, sexual abuse, or physical trauma. Physical examination showed ulceration and swelling of the labia minora, and the patient received an empiric dose of acyclovir (200 mg 4 times daily) for presumed autoinoculated herpes simplex virus (HSV) infection. An ulcer swab was performed, and urinalysis revealed no evidence of infection. Two days later, the patient presented to the emergency department with increasing vulvar pain and vaginal discharge. The previous ulcer swab findings were negative for HSV (PCR assay), and consequently, acyclovir was discontinued after 1 day of therapy. She received topical viscous lidocaine and an empiric dose of oral fluconazole. The lidocaine provided temporary symptomatic relief. Results of DNA amplification studies were negative for Chlamydia trachomatis and Neisseria gonorrhoeae. A potassium hydroxide preparation was negative for fungi, and an ulcer swab for bacterial culture revealed usual flora. Of note, the PCR assay for Epstein-Barr virus was not performed on ulcer cells. The patient was referred to the department of dermatology, and results of a physical examination showed copious white mucoid discharge and a 2-cm ulceration of the left labia minora (Figure, panel A). Two smaller pinpoint ulcerations and swelling of the left labia minora were also noted. The lesions were clinically indistinguishable from the genital aphthous ulcers of patients with complex aphthosis (recurrent, severe aphthous ulcers on oral or genital mucosa). A diagnosis of ulcus vulvae acutum was made, and treatment was started with clobetasol 0.05% ointment (4 times daily) and lidocaine gel as needed. Four days later, the patient reported marked symptomatic improvement. Physical examination showed near resolution of the large vulvar ulceration (Figure, panel B). The patient tapered use of clobetasol ointment over the next several days until the ulcerations healed completely. Two months after her initial episode, the patient again had 3 small vulvar erosions after symptoms that included low-grade fever, malaise, and vomiting. She did not receive oseltamivir for this illness; clobetasol ointment was applied 4 times daily, and the vulvar erosions ameliorated within a few days. Her constitutional symptoms resolved without treatment. The patient has not experienced any further episodes of vulvar ulcerations in the 18 months after the most recent treatment.

A new model for dermatitis herpetiformis that uses HLA-DQ8 transgenic NOD mice.

Dermatitis herpetiformis (DH) is an autoimmune blistering skin disorder that is associated with gluten sensitivity. It presents as a papulovesicular rash and is often associated with enteropathy. The rash resolves when the patient is placed on a gluten-free diet and/or dapsone. DH, as well as celiac disease, is tightly associated with DQ2 and DQ8. A novel mouse model for DH is described that utilizes the NOD background and the HLA-DQ8 transgene. The addition of DQ8 contributes sensitivity to gliadin, and the addition of the NOD background contributes to autoimmunity and pathogenesis. Fifteen NOD DQ8+ mice of 90 that were sensitized to gluten developed blistering pathology similar to that seen in DH. Neutrophil infiltration of the dermis, deposition of IgA at the dermal-epidermal junction, and a complete reversal of the blistering phenomenon with the administration of a gluten-free diet with or without dapsone were observed. None of the 3 blistering mice examined had small-bowel pathology. This animal model of DH will be useful to determine the specificity of the IgA deposits, as well as the pathogenic mechanisms that occur in the skin as a result of gluten ingestion.

Contact allergy in oral disease.

BACKGROUND: The role of contact allergy in oral cavity disease processes is unknown. OBJECTIVE: We sought to determine the prevalence of contact allergy to flavorings, preservatives, dental acrylates, medications, and metals in patients with oral disease. METHODS: Patients were tested with an 85-item oral antigen screening series. Data were analyzed retrospectively. RESULTS: We evaluated 331 patients with burning mouth syndrome, lichenoid tissue reaction, cheilitis, stomatitis, gingivitis, orofacial granulomatosis, perioral dermatitis, and recurrent aphthous stomatitis. Positive patch test results were identified in 148 of the 331 patients; 90 patients had two or more positive reactions. Allergens with the highest positive reaction rates were potassium dicyanoaurate, nickel sulfate, and gold sodium thiosulfate. Of the 341 positive patch test reactions, 221 were clinically relevant. LIMITATIONS: No follow-up data were available in this retrospective analysis. CONCLUSION: The positive and relevant allergic reactions to metals, fragrances, and preservatives indicated that contact allergy may affect oral disease.

Contact stomatitis.

Contact stomatitis occurs in up to 10% of the population. Mechanical or chemical irritation, ill-fitting dentures, and dental fillings can induce irritant contact stomatitis. Type I hypersensitivity and type IV hypersensitivity to dental products and foods are frequently responsible for the allergic types of contact stomatitis. We review the causal agents of contact stomatitis, the differential diagnoses, diagnostic testing, and potential treatment.

A Diagnostic Approach to Recurrent Orofacial Swelling: A Retrospective Study of 104 Patients.

OBJECTIVE: To identify patients evaluated in an outpatient setting at our institution with a presentation of recurrent orofacial swelling and to review the spectrum of causes to outline a diagnostic approach. PATIENTS AND METHODS: A retrospective study of 104 patients with more than 1 episode of orofacial swelling lasting for more than 5 days identified through a keyword search of the electronic health record from January 2, 2000, through July 5, 2011. RESULTS: Patients were categorized according to final cause of orofacial swelling: idiopathic orofacial granulomatosis, solid facial edema due to rosacea and acne vulgaris, Crohn disease, contact dermatitis, sarcoidosis, exfoliative cheilitis, lichen planus, actinic cheilitis, cheilitis glandularis, lymphedema, miscellaneous, and multifactorial. Granulomatous inflammation was noted on biopsy in 40 of 85 patients (47%). Oral involvement was associated with Crohn disease (P<.001), and facial and periorbital swelling was associated with solid facial edema in the setting of rosacea and acne vulgaris (P<.001). CONCLUSION: The broad range of diagnoses responsible for recurrent orofacial swelling underscores the diagnostic challenge and importance of a thorough multidisciplinary evaluation to identify underlying causes.

Childhood stye and adult rosacea.

BACKGROUND: Little is known about how individuals with a predisposition for rosacea appear in childhood. This retrospective, matched control, longitudinal study examined the relationship between childhood stye and adult rosacea. METHODS: The records of the Rochester Epidemiology Project were examined to identify patients who received care for stye or blepharitis between ages 2 and 17 years, and received care for any cause at age 40 years or older. Patients were matched by group to control subjects (1:2). RESULTS: Patients with stye during childhood (N = 201) had a higher prevalence of adult rosacea than did control subjects (5.5% vs 1.5%, P = .01). Patients who had other childhood eye conditions without stye (N = 504) were not at higher risk. LIMITATIONS: The study population included few minority patients. CONCLUSIONS: The association between childhood stye and adult rosacea appears to be significant and should be examined further. Rosacea prevalence in adults may be lower (2.1%) than previously reported.

Oral and vulvar changes in pregnancy.

The endocrinologic, immunological, and vascular changes that occur during pregnancy are far-reaching. These systemic factors produce profound local impact on the physiology and pathology of the oral cavity, vagina, and vulva. Physiological changes can be expected and tolerable or of such severity that they are viewed as pathological. Existing disease can be exacerbated and dermatoses specific to pregnancy can erupt. Each of these conditions can pose potentially challenging treatment considerations.

Atrophic glossitis from vitamin B12 deficiency: a case misdiagnosed as burning mouth disorder.

BACKGROUND: Glossodynia, or painful sensation of the tongue, can have a spectrum of etiologies, such as local infection, trauma, nerve damage, glossitis, or the enigmatic neuropathic pain syndrome, burning mouth disorder (BMD; also known as burning mouth syndrome). Careful history-taking, physical examination, and appropriate laboratory screening can differentiate these causes of glossodynia and direct further therapy. METHODS: A 73-year-old woman presented with several months of glossodynia having previously been diagnosed by her primary care physician with primary BMD. Subsequently, she consulted an otolaryngologist, who pursued further diagnostic evaluation. RESULTS: Examination revealed the presence of a beefy, red, smooth tongue, and further laboratory evaluation yielded a low serum vitamin B(12) level and macrocytosis. Three months of oral vitamin B(12) supplementation led to partial restoration of serum vitamin B(12) levels and a modest improvement in symptoms. Her final diagnoses were atrophic glossitis and glossodynia secondary to vitamin B(12) deficiency, most likely due to pernicious anemia. CONCLUSIONS: The results of this case have important clinical implications for the diagnostic evaluation and management of patients with glossodynia and apparent BMD. Pathogenic mechanisms of nutrient deficiency in atrophic glossitis are discussed.

Acute oral ulcers.

Accurate diagnosis of acute oral ulcers can be challenging. Important historic details include the pattern of recurrence, anatomic areas of involvement within the mouth and elsewhere on the mucocutaneous surface, associated medical symptoms or comorbidities, and symptomology. Careful mucocutaneous examination is essential. When necessary, biopsy at an active site without ulceration is generally optimal. Depending on the clinical scenario, supplemental studies that may be useful include cultures; perilesional biopsy for direct immunofluorescence testing; and evaluation for infectious diseases, gluten sensitivity, inflammatory bowel disease, human immunodeficiency virus infection, connective tissue diseases, or hematinic deficiencies. Clinicians should maintain a broad differential diagnosis when evaluating patients with acute oral ulcers.

Recurrent aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) is the most common acute oral ulcerative condition in North America. RAS is divided into a mild, common form, simple aphthosis, and a severe, less common form, complex aphthosis. Aphthosis is a reactive condition. The lesions of RAS can represent the mucosal manifestation of a variety of conditions. These include conditions with oral and genital aphthae such as ulcus vulvae acutum, reactive nonsexually related acute genital ulcers, and Behçet disease. The mouth is the beginning of the gastrointestinal (GI) tract, and the lesions of RAS can be a manifestation of GI diseases such as gluten-sensitive enteropathy, ulcerative colitis, and Crohn disease. Complex aphthosis may also have correctable causes. The clinician should seek these in a careful evaluation. Successful management of both simple and complex aphthosis depends on accurate diagnosis, proper classification, recognition of provocative factors, and the identification of associated diseases. The outlook for patients with both simple and complex aphthosis is positive.

Oral lichen planus.

Lichen planus is an inflammatory mucocutaneous disease that can affect the skin, hair, nails, and mucosal surfaces. Mucosal sites of involvement include oral, genital, ocular, otic, esophageal, and, less commonly, bladder, nasal, laryngeal, and anal surfaces. Oral lichen planus is a mucosal variant of lichen planus, which tends to affect women more often than men, with a typically more chronic course and potential for significant morbidity. Treatment can be challenging, and there is potentially a low risk of malignant transformation; however, therapeutic benefits can be obtained with various topical and systemic medications. Clinical monitoring is recommended to ensure symptomatic control. Increasing awareness and recognition of this entity have continued to fuel advances in therapy and in our understanding of the disease.

Diseases of the tongue.

The tongue is a complex organ involved in speech and expression as well as in gustation, mastication, and deglutition. The oral cavity, along with the tongue, are sites of neoplasms, reactive processes, and infections, and may be a harbinger of systemic diseases. This review includes both common and rare diseases that occur on the tongue, including: vascular and lymphatic lesions (infantile hemangiomas and oral varices), reactive and inflammatory processes (hairy tongue, pigmented fungiform papillae of the tongue, benign migratory glossitis, and fissured tongue), infections (oral hairy leukoplakia, herpes simplex and varicella-zoster virus infections, human papillomavirus, and candidiasis), premalignant lesions (leukoplakia and erythroplakia), malignant lesions (squamous cell carcinoma, Kaposi sarcoma, and lymphoproliferative diseases), and signs of systemic disease (nutritional deficiency and systemic amyloidosis).

Orofacial granulomatosis.

Orofacial granulomatosis (OFG) is an uncommon chronic granulomatous condition with a multifactorial etiology and pathogenesis. Genetic, immunologic, allergic, and infectious mechanisms have been implicated. OFG is often used as a descriptor to encompass all entities with orofacial swelling and histologic evidence of noncaseating granulomas. The diagnosis of OFG should prompt evaluation for provocative factors. The cause of most cases of OFG remains obscure. The clinician must consider mycobacterial infections, deep fungal infections, sarcoidosis, rosacea, and Crohn disease (CD). In addition, OFG should be considered synonymous with previously described conditions, including granulomatous cheilitis and Miescher cheilitis, as well as Melkersson-Rosenthal syndrome and its monosymtomatic or oligosymptomatic variants. The relationship of OFG to CD is currently debated, with recent evidence suggesting the possibility of three entities: classic oral CD (established gastrointestinal CD with oral involvement), OFG with gastrointestinal involvement (OFG with subclinical or asymptomatic gastrointestinal endoscopy changes), and OFG without bowel involvement. Childhood onset, presence of certain phenotypic features, laboratory abnormalities, or gastrointestinal symptoms may indicate the need for further evaluation to assess for concurrent or future CD. Although multiple therapies have been found to be effective in small numbers of patients, treatment should be tailored to each patient.

Clinical features of Behçet's disease: A retrospective chart review of 26 patients.

BACKGROUND: Behçet's disease (BD) is a multi-organ inflammatory disorder with mucocutaneous, ocular, neurological, musculoskeletal, gastrointestinal, and pulmonary manifestations. The aim of this study was to determine the clinical features of BD in a cohort of patients diagnosed at the University of California, Davis, United States. METHODS: The medical records of 59 patients with an ICD9-code of BD were retrospectively reviewed. The International Criteria for BD was used to identify patients with a point score ≥5. The clinical manifestations of BD were investigated over a 10-year period in this cohort. RESULTS: Twenty-six patients (20 women, six men; female:male ratio = 3.3:1.0) had a point score ≥5 based on the International Criteria. The average age of onset of BD was 29.25 ± 14.25 years. Oral ulcers (100%), genital ulcers (84.6%), articular involvement (69.2%), ocular involvement (65.3%), and skin lesions (50.0%) were the most prevalent manifestations of BD in this cohort. CONCLUSION: Oral ulcers were the most common presenting and lifetime sign of BD. In our cohort, oral and genital ulcers were hallmarks of BD, independent of patient demographics. Thus, patients with these signs require close surveillance for other manifestations of the disease.