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Recurrent aphthous stomatitis (RAS) is the most common idiopathic intraoral ulcerative disease in the USA. Aphthae typically occur in apparently healthy individuals, although an association with certain systemic diseases has been reported. Despite the unclear etiopathogenesis, new drug trials are continuously conducted in an attempt to reduce pain and dysfunction. We investigated four controversial topics: (1) Is complex aphthosis a mild form of Behçet’s disease (BD)? (2) Is periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome a distinct medical entity? (3) Is RAS associated with other systemic diseases (e.g., celiac disease and B12 deficiency)? (4) Are there any new RAS treatments? Results from extensive literature searches, including a systematic review of RAS trials, suggested that: (1) Complex aphthosis is not a mild form of BD in North America or Western Europe; (2) Diagnostic criteria for PFAPA have low specificity and the characteristics of the oral ulcers warrant further studies; (3) Oral ulcers may be associated with celiac disease; however, these ulcers may not be RAS; RAS is rarely associated with B12 deficiency; nevertheless, B12 treatment may be beneficial, via mechanisms that warrant further study; (4) Thirty-three controlled trials published in the past 6 years reported some effectiveness, though potential for bias was high.

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It is strange that the existence of oral psoriasis seems so rare. Other papulosquamous disorders, such as lichen planus, are frequently associated with oral manifestations, yet oral psoriasis is rare given the prevalence of cutaneous disease. One explanation is that oral lesions are asymptomatic and do not come to the clinician's attention. Other explanations, however, are necessary. Epithelial turnover time is significantly increased in psoriatic plaques and may be as rapid as 3 to 7 days, whereas normal epithelial turnover is 28 days. Some have suggested that this abnormally increased turnover time in psoriasis approximates that of the normal regenerative time of the oral epithelium, and this possibility may account for the apparent lack of changes in the oral mucosa of patients with psoriasis [1]. It is also possible that oral lesions of psoriasis are altered both clinically and histologically by other factors within the oral microenvironment and are not recogized. Although controversy has appeared in the literature about whether lesions of oral psoriasis exist, there is sufficient evidence that a subset of patients have oral lesions in association with skin disease. This occurrence is more common in patients with the severe forms of psoriasis, such as generalized pustular psoriasis. The diagnosis of oral psoriasis should be based on good clinical and histologic evidence, and, in general, the clinical course of the oral lesions should parallel that of the skin disease. Exclusion of other causes is important, particularly if cutaneous lesions are absent and a diagnosis of isolated oral psoriasis is entertained. Because neither the clinical nor the histologic changes are absolutely specific for psoriasis, the patient requires holistic evaluation. That being said, in day-to-day practice it is most likely not practical to obtain a biopsy of asymptomatic oral lesions for definitive histologic or immunofluorescence studies. The clinician, however, must have a high degree of awareness and pay close attention to the oral mucosa in patients with psoriasis. A thorough examination is imperative, because asymptomatic oral lesions may be found more frequently in patients with psoriasis if clinicians habitually check mucous membranes during the generalized skin examination. Conversely, in patients with troublesome oral lesions, a cutaneous examination that reveals subtle changes suggestive of psoriasis may provide clues to the oral diagnosis. A detailed history remains the cornerstone of diagnosis, because a family history of psoriasis or a history of psoriasis now in remission may guide physicians when they note oral lesions.

Oral mucositis (OM) is a debilitating early adverse effect of allogeneic hematopoietic stem cell transplantation (HSCT). The intensity of the conditioning regimen correlates with the incidence and severity of OM, but no studies have analyzed this relationship among various conditioning regimens. We performed a systematic review on the incidence and outcomes of OM in allogeneic HSCT patients and analyzed this association. A comprehensive search of several databases (Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Cochrane CRCT, Cochrane DSR, Scopus) from 1990 to 2014 for studies of OM in allogeneic HSCT patients was conducted. Professional societies' meeting abstracts were also searched. Grade of OM was analyzed based on the World Health Organization (WHO) or National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events scales. Severe mucositis was defined as either grades 2 to 4 or grades 3 and 4, depending on the studies' definition of severity. Cohorts were analyzed based on regimen intensity; ie, reduced-intensity conditioning (RIC) (including nonmyeloablative) and myeloablative (MA). Random effect (RE) and standard logistic models weighted by the number of patients in each cohort were used for comparisons. A total of 624 studies were generated from the search. Of the 395 patients in 8 eligible MA regimen studies, 73.2% experienced any OM, whereas in 245 patients in the 6 eligible RIC regimen studies, 86.5% experienced any OM (chi-square P < .0001; RE, P = .05). Severe (grades 2 to 4) OM occurred among 79.7% of the WHO/NCI-graded MA patients and 71.5% of RIC patients (chi-square, P = .0421; RE, P < .01). In comparing graft-versus-host disease (GVHD) prophylaxis, only 55.4% of patients receiving nonmethotrexate regimens experienced OM; this was lower (chi-square, P < .0001; RE, P = .06) than that found among patients who received methotrexate (83.4%), either standard or reduced dose. Besides NCI and WHO grading scales, other scales included in the studies were Oral Mucositis Index, the Southwest Oncology Group Criteria, and Eastern Cooperative Oncology Group scale. To our knowledge, this is the first analysis on OM in allogeneic HSCT patients with respect to conditioning regimens, and we observed that RIC regimens led to a high incidence of OM similar to that of MA regimens. Clinical trials on treatment of OM are lacking, emphasizing the essential need for prospective studies in this arena. A significant variance in the criteria for grading OM underscores the importance of establishing a standard grading system for OM measurement in future allogeneic HSCT clinical trials.

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