Mutations in IL36RN are associated with geographic tongue.

Geographic tongue (GT) is a benign inflammatory disorder of unknown etiology. Epidemiology and histopathology in previous studies found that generalized pustular psoriasis (GPP) is a factor associated with GT, but the molecular mechanism remains obscure. To investigate the mechanism of GT, with and without GPP, three cohorts were recruited to conduct genotyping of IL36RN, which is the causative gene of GPP. In a family spanning three generations and diagnosed with only GT ("GT alone"), GT was caused by the c.115+6T>C/p.Arg10ArgfsX1 mutation in the IL36RN gene. An autosomal dominant inheritance pattern with incomplete penetrance was observed. In the cohort consisting of sporadic cases of "GT alone" (n = 48), significant associations between GT and three IL36RN variants (c.115+6T>C/p.Arg10ArgfsX1, c.169G>A/p.Val57Ile and c.29G>A/p.Arg10Gln) were shown. In the GPP patient cohort (n = 56) and GPP family member cohort (n = 67), a significant association between the c.115+6T>C mutation and the simultaneous presence of GPP and GT was observed when compared to the presence of GPP without GT (P < 0.05). Biopsies revealed similarities among GT patients with different genotypes (AA, Aa and aa), with the neutrophils prominently infiltrating the epidermis. Western-blot analysis showed that the expression ratio of IL-36Ra/IL-36γ in lesioned tongues with individuals harboring different genotypes (AA, Aa and aa, n = 3, respectively) decreased significantly compared to controls (n = 3). We describe the mechanism of GT for the first time: some cases of GT are caused by IL36RN mutations, while those lacking mutations are associated with an imbalance in expression between IL-36Ra and IL-36γ proteins in tongue tissue.

[Erythema migrans as a patognomic symptom of lyme disease]. / Rumien wedrujacy jako patognomoniczny objaw boreliozy z lyme.

Erythema migrans (EM) is an early localized form of Lyme borreliosis (LB). EM appears 3-30 days after tick bite and presents as annular homogenous erythema, marked from unaffected skin. Typical EM has more than 5 cm in diameter, but there are reports of mini-EM in literature. Moreover, multiple or bullous EM are described. Diagnosis is based on clinical picture. In treatment antibiotics must be used. The aim of this paper was to draw attention to still existing problem of LB in Poland, not only in endemic areas and to the necessity of proper diagnosis, early implementation of antibiotics. It may prevent from late form of LB development, which may lead to irreversible damage, especially in nervous system or joints. EM presence in history increases the probability of subsequent LB forms such as neuroborreliosis or arthritis. Otherwise, symptoms may be misinterpreted, as they resemble the other in the course of more common diseases.

Treatment of erythema migrans with doxycycline for 10 days versus 15 days.

BACKGROUND: The efficacy of 10-day doxycycline treatment in patients with erythema migrans has been assessed in the United States but not in Europe. Experts disagree on the significance of post-Lyme borreliosis symptoms. METHODS: In a noninferiority trial, the efficacies of 10 days and 15 days of oral doxycycline therapy were evaluated in adult European patients with erythema migrans. The prevalence of nonspecific symptoms was compared between patients with erythema migrans and 81 control subjects without a history of Lyme borreliosis. The efficacy of treatment, determined on the basis of clinical observations and microbiologic tests, was assessed at 14 days and at 2, 6, and 12 months. Nonspecific symptoms in patients and controls were compared at 6 months after enrollment. RESULTS: A total of 117 patients (52%) were treated with doxycycline for 15 days, and 108 (48%) received doxycycline for 10 days. Twelve months after enrollment, 85 of 91 patients (93.4%) in the 15-day group and 79 of 86 (91.9%) in the 10-day group had complete response (difference, 1.6 percentage points; upper limit of the 95% confidence interval, 9.1 percentage points). At 6 months, the frequency of nonspecific symptoms in the patients was similar to that among controls. CONCLUSIONS: The 10-day regimen of oral doxycycline was not inferior to the 15-day regimen among adult European patients with solitary erythema migrans. Six months after treatment, the frequency of nonspecific symptoms among erythema migrans patients was similar to that among control subjects. CLINICAL TRIALS REGISTRATION: NCT00910715.

Oral manifestations of psoriasis. Clinical presentation and management.

Psoriasis is a chronic immune-mediated disease of unknown etiology that affects the skin and mucous membranes. According to the National Institutes of Health (NIH), approximately five million Americans, 3% of the population, have been diagnosed with psoriasis. Oral manifestations of psoriasis are less well recognized than skin lesions, and treatment for oral lesions is not standardized. This article will review the clinical presentation of skin and mucous membrane psoriasis, along with the therapeutic modalities available to oral health-care providers.

Antimicrobial action of calprotectin that does not involve metal withholding.

Calprotectin is a potent antimicrobial that inhibits the growth of pathogens by tightly binding transition metals such as Mn and Zn, thereby preventing their uptake and utilization by invading microbes. At sites of infection, calprotectin is abundantly released from neutrophils, but calprotectin is also present in non-neutrophil cell types that may be relevant to infections. We show here that in patients infected with the Lyme disease pathogen Borreliella (Borrelia) burgdorferi, calprotectin is produced in neutrophil-free regions of the skin, in both epidermal keratinocytes and in immune cells infiltrating the dermis, including CD68 positive macrophages. In culture, B. burgdorferi's growth is inhibited by calprotectin, but surprisingly, the mechanism does not involve the classical withholding of metal nutrients. B. burgdorferi cells exposed to calprotectin cease growth with no reduction in intracellular Mn and no loss in activity of Mn enzymes including the SodA superoxide dismutase. Additionally, there is no obvious loss in intracellular Zn. Rather than metal depletion, we find that calprotectin inhibits B. burgdorferi growth through a mechanism that requires physical association of calprotectin with the bacteria. By comparison, calprotectin inhibited E. coli growth without physically interacting with the microbe, and calprotectin effectively depleted E. coli of intracellular Mn and Zn. Our studies with B. burgdorferi demonstrate that the antimicrobial capacity of calprotectin is complex and extends well beyond simple withholding of metal micronutrients.

Successful treatment with cyclosporin administration for persistent benign migratory glossitis.

We herein describe a 54 year-old female patient with a 5-year history of persistent and painful benign migratory glossitis (BMG), which was remarkably improved by systemic administration of cyclosporin. She had noted some white patches leaving smooth denuded red areas with whitish elevated borders on the dorsum of her tongue, and finally felt strong pain. The lesion was refractory to the previous treatment with topical corticosteroid treatment for the last 2 years. Because clinicopathological findings were compatible with BMG, systemic administration of 20 mg/day prednisolone and topical 0.1% dexamethasone application were started, however, she suffered a severe relapse after tapering the dosage of prednisolone to 10 mg/day. Because some investigations have suggested that BMG is an oral manifestation of psoriasis, we introduced cyclosporin administration. The systemic treatment of cyclosporin microemulsion pre-concentrate, 3 mg/kg/day, resulted in a satisfactory improvement. Two months later, we could reduce cyclosporin microemulsion pre-concentrate dosage to 1.5 mg/kg/day for maintenance therapy, and the disease has been well controlled so far.

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).

Dilemma in treatment of patients suffering from orofacial dysaesthesia.

A retrospective study of 64 patients with orofacial dysaesthesia is presented. Special emphasis is placed on the patients' symptoms and on the manipulative treatments they received before they were referred for psychiatric consultation. The patients had suffered from chronic orofacial pain or feelings of discomfort for periods ranging from 6 months up to 25 years. The patients had visited several specialists and had received numerous manipulative or medical treatments, the most common of which were repeated medication (drug treatment), TMJ dysfunction treatment, endodontic or exodontic treatment, and surgical explorations. However, the success of all these clinical efforts was very limited because of the apparent psychosomatic origin of the complaints. This study clearly shows that psychiatric consultations are still too seldom made in patients with chronic orofacial dysaesthesia, that many patients have a mental disorder, and that most chronic psychosomatic pain disorders are treated as acute specific pain.

The treatment of geographic tongue with topical Retin-A solution.

A new treatment for geographic tongue with topically applied tretinoin is suggested and its effective use on three patients is described.

Treatment approaches to common symptomatic oral lesions in children.

A variety of oral mucosal lesions can be symptomatic in children. This article describes the classic clinical appearance of the most common oral diseases and provides treatment recommendations that are tailored to the pediatric age group. When possible, more than one drug alternative is given for each of the different oral conditions for an improved success rate. It is essential for the clinician to understand that this article should be used as a guide for managing oral and perioral lesions in children and adolescents. Specific dosages and formularies of drugs may require modification in the young child. Consultation with a primary care physician and pharmacist often is needed to ensure the best possible outcome, especially when immunosuppressive drugs are indicated. Most importantly, oral lesions that do not respond to therapeutic protocols should be referred to the appropriate specialist for definitive diagnosis and treatment.

Treatment of geographic tongue with topical tacrolimus.

Geographic tongue is an inflammatory condition of the dorsal surface and lateral border of the tongue, which may be asymptomatic. This article presents a case of geographic tongue in a 6-year-old child. Successful management was achieved with topical application of 0.1% tacrolimus.

Functional outcomes in patients with Borrelia burgdorferi reinfection.

When Lyme disease is treated with appropriate antibiotic therapy in the early stages, long-term outcomes are good. However, a few patients have persistent symptoms despite appropriate therapy. Whether these patients' symptoms are any different from those of patients with reinfection is unclear. Our objective was to compare long-term symptoms and functional outcomes of patients with Borrelia burgdorferi reinfection with those of patients with only 1 episode of infection and with no history of infection. We compared outcomes of Lyme reinfection patients, characterized by recurrent erythema migrans (EM) lesions, with those of patients with 1 episode of Lyme disease (Lyme control) and with no history of Lyme disease (non-Lyme control) by retrospective medical record review and a survey consisting of a 36-item Short-Form Health Survey (SF-36) and a 10-item symptom questionnaire. Analysis of variance (ANOVA) for continuous variables and χ(2) analysis for categorical variables were used. In cases of low cell counts, Fisher's exact tests were used. Bonferroni correction was used for multiple comparisons when ANOVA was significant. Reinfection was identified in 23/673 (3.4%) patients who had a diagnosis of Lyme disease in our health system during 2000-2004. Of the 23, 15 had long-term follow-up data and were age- and sex-matched to 45 Lyme control and 60 non-Lyme control group patients. Clinical characteristics were similar in the reinfection and Lyme control groups. SF-36 results were similar between groups for all domains except energy/vitality (VT). The SF-36 domain of VT was significantly different between groups: 63.0 vs. 54.5 vs. 64.5 in the reinfection, Lyme control, and non-Lyme control groups, respectively (p=0.047). Clinical features and long-term outcomes of patients with recurrent EM lesions were similar to those of the control groups and consistent with B. burgdorferi reinfection, not persistent infection. Patients with Lyme reinfection should be treated with antibiotic regimens similar to those used for patients with an initial episode of Lyme disease.

Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease.

Evidence-based guidelines for the management of patients with Lyme disease were developed by the International Lyme and Associated Diseases Society (ILADS). The guidelines address three clinical questions - the usefulness of antibiotic prophylaxis for known tick bites, the effectiveness of erythema migrans treatment and the role of antibiotic retreatment in patients with persistent manifestations of Lyme disease. Healthcare providers who evaluate and manage patients with Lyme disease are the intended users of the new ILADS guidelines, which replace those issued in 2004 (Exp Rev Anti-infect Ther 2004;2:S1-13). These clinical practice guidelines are intended to assist clinicians by presenting evidence-based treatment recommendations, which follow the Grading of Recommendations Assessment, Development and Evaluation system. ILADS guidelines are not intended to be the sole source of guidance in managing Lyme disease and they should not be viewed as a substitute for clinical judgment nor used to establish treatment protocols.

Geographic tongue and tenofovir.

A 55-year-old male patient with chronic hepatitis B was started on tenofovir. One month after initiating the new medication, he developed severe symptomatology with odynophagia and a very painful tongue. The physical examination reveals multiple erythematous patches on his tongue and a biopsy was performed. It allowed the diagnosis of benign migratory glossitis or geographic tongue. The patient was kept on tenofovir, but had to start topical corticoid therapy. Geographic tongue is a common condition that may be caused by drug idiosyncrasy, but has never before been associated to tenofovir. It is usually asymptomatic, but sometimes it causes severe symptoms, being an important impairment of quality of life.