To the Editor:
Recurrent aphthous stomatitis (RAS) is a mucocutaneous condition characterized by single or multiple, painful,1,2 round ulcerations of variable sizes with a tendency for recurrence, most commonly located in nonkeratinized areas of the oral mucosa. Pathergy commonly is observed.3 Although many authors consider the terms RAS andaphtha to be synonymous,4,5 differentiating the clinical lesion (aphthous ulceration) from the disease (aphtha or RAS) can be useful, as several other diseases can at times manifest with similar ulcers (called aphthoid lesions), such as pemphigus vulgaris, mucous membrane pemphigoid, and erythema multiforme.6
It is estimated that approximately 20% of individuals worldwide have at least one episode of aphtha during their lifetime,7 and it is considered the most common disease of the oral mucosa.8,9 However, only patients presenting with severe acute outbreaks or frequent relapses typically seek medical treatment. Clinically, aphthous ulcers are classified as aphtha minor (small number of small lesions), aphtha major (large deep lesions that also can affect the minor salivary glands with intense necrosis, difficulty in healing, and mucosal scarring), and aphtha herpetiformis (innumerous tiny lesions that reappear in recurring outbreaks).1-3 The term complex aphthosis was introduced in 198510 and is defined as recurrent oral and genital aphthous ulcerations or recurring multiple oral aphthous ulcers in the absence of systemic manifestations or Behçet disease11,12; however, complex aphthosis also has been reported as frequent episodes of ulcerations that may be associated with systemic diseases including Behçet disease.13,14
Currently, RAS is considered an immunologically mediated alteration in cutaneous mucosal reactivity with a multifactorial systemic cause. Underlying conditions such as Behçet disease, inflammatory bowel disease (IBD), iatrogenic immunosuppression (eg, following solid organ transplantation), AIDS, and cyclic neutropenia may or may not be detected.11-13
Our retrospective study explored the systemic nature of RAS. We reviewed patient records to evaluate underlying systemic conditions associated with the diagnosis of RAS and the use of oral medications in managing the disease. Medical records from the Department of Dermatology of the University of São Paulo, Brazil, from 2003 to 2017 were reviewed to identify patients with a diagnosis of RAS. Clinical classification of RAS—minor, major, or herpetiform—as well as the presence of aphthous lesions in other locations and the presence of other associated inflammatory cutaneous manifestations also were noted. Associated systemic diseases and treatments for RAS were recorded. Patients for whom the diagnosis of RAS was changed during follow-up were excluded. Because this was a retrospective analysis of medical records and without any patient risk, informed consent was not needed.
Medical records for 125 patients were reviewed; 63 were male (50.4%), and 62 were female (49.6%). The age at onset of symptoms, which ranged from a few months after birth to 74 years, was reported in only 92 (73.6%) patient medical records. Of these, 30 (32.6%) reported onset before 20 years of age, 39 (42.4%) between 20 and 39 years, 17 (18.5%) between 40 and 59 years, and 6 (6.5%) at 60 years or older. Morphologically, 72 (57.6%) had minor, 42 (33.6%) had major, and 11 (8.8%) had herpetiform aphthous ulcers. None of the patients presented with sporadic lesions; the disease was long-standing and persistent in all cases (complex aphthosis).
Regarding the location of the ulcers, 92 (73.6%) patients had lesions on the oral mucosa only. Some patients had lesions in more than one site in addition to the oral mucosa: 32 (25.6%) had aphthae in the genital/groin region and 4 (3.2%) presented with perianal/anal aphthae. Nineteen patients (19.2%) presented other cutaneous manifestations in addition to aphthae: 11 (45.8%) had folliculitis/pseudofolliculitis, and 8 (33.3%) had erythema nodosum (EN). Eight patients (33.3%) presented with uveitis, and 6 (25%) presented with concomitant arthralgia/arthritis. Fifty-four patients (43.2%) had confirmed or suspected associated disease: Behçet disease (21 [38.9%]), IBD (10 [18.5%]), solid organ transplantation (7 [13.0%])(kidney, 4 [57.1%]; heart, 2 [28.6%]; liver, 1 [14.3%]), HIV infection (6 [11.1%]), lymphoma (1 [1.9%]), aplastic anemia (1 [1.9%]), or myelodysplastic syndrome (1 [1.9%]). Ten patients (18.5%) presented with other diseases under investigation (eg, unidentified rheumatologic disease, unexplained neutropenia, undiagnosed immunodeficiencies, autoinflammatory syndromes, possible cyclic neutropenia).
Biopsies of the oral mucosa were performed in 31 patients. Histopathologic findings will be discussed in a future publication (unpublished data).