Simple And Complex Aphthosis

The presence of the lesions of RAS is critical to the diagnosis of BD12. The diagnosis is rarely made in the absence of oral aphthosis. Aphthosis can be classified as simple aphthosis or complex aphthosis (Table 1). Patients with BD typically have complex aphthosis. Simple aphthosis is a common, episodic, short-lived type of RAS affecting 20-50% of the population in their youth1,6,7. Complex aphthosis is an uncommon, persistent, chronic type of RAS which may be associated with systemic diseases1,4,5,8. Complex aphthosis patients may have anogenital aphthae. The presence of oral plus anogenital aphthae does not constitute a diagnosis of BD. The condition might be considered a forme fruste of BD5, but the diagnosis of complex aphthosis is preferable to making an inaccurate diagnosis of BD.

Table 1. Classification of Recurrent Aphthous Stomatitis

Simple Aphthosis

Complex Aphthosis




Episodic or continuous

Short-lived lesions


Few lesions

Few to many lesions

3-6 episodes/year

Frequent or continuous


Prompt healing

Slow healing

Minimal pain

Marked pain

Little disability


Limited to oral cavity

May have genital lesions

The recurrent aphthae of both simple and complex aphthosis are classified morphologically as minor aphthous ulcers (MiAU), major aphthous ulcers (MjAU), and herpetiform ulcers (HU)6,9. Some authors note an increased prevalence of MjAU in patients with BD when compared to all patients with RAS10.

Successful management of patients with complex aphthosis requires an accurate diagnosis, classification of the disease, and recognition of causal or associated conditions. It is incumbent on the clinician to evaluate the patient with complex aphthosis for these conditions. Correction of the underlying condition such as gluten-sensitive enteropathy (GSE) by a gluten-free diet can result in a substantial diminution of disease activity or a remission11.

Ulcus vulvae acutum represents an acute severe episode of oral and vulvar aphthae often associated with an infectious gastroenteritis such as tuberculous enterocolitis, typhoid fever, or Yersinia enterocolitis. Upon recovery, simple aphthosis may remain as the only remnant of the disease. Patients with rare combinations of signs and symptoms in the context of complex aphthosis have been reported as the MAGIC syndrome (mouth and genital ulcers with inflamed cartilage), the FAPA syndrome (fever, aphthosis, pharyngitis, and adenitis), and cyclic neutropenia. Aphthous-like oral ulcerations have been reported in HIV-positive patients. Lesions tend to be large and disabling. These lesions of complex aphthosis tend to occur in individuals with CD4+ counts<100 cells/mL. The differential diagnosis of this profound immunosuppressive state includes infectious or drug-induced oral ulcers. The diagnosis of HIV-associated aphthous-like oral ulcers is one of exclusion.

Anemia and hematinic deficiencies have been associated with lesions of RAS for many years. Several studies have confirmed the presence of a subset of patients who may be deficient in iron, folic acid, zinc, vitamins B1, B2, B6, and B12 and whose disease remits or improves dramatically with replacement of their deficiencies12-14. Hematological screening should be considered for all patients with complex aphthosis, those patients with persistently troublesome signs and symptoms, and any patients with signs or symptoms of malabsorption or nutritional deficiency. Screening includes a complete blood count with red blood cell indices; serums levels of iron, zinc, and vitamin B12; red blood cell or serum folate; and anti-endomysial, anti-gliadin antibody, or tissue transglutaminase studies.

Gastrointestinal diseases have been associated with lesions of RAS for many years. Indeed, according to DuBois and van den Berghe15, the word "sprue," signifying the gastrointestinal disease, is derived from the Dutch word "spruw" which means aphthosis. The association of lesions of RAS with GSE/sprue has been recognized previously11. The malabsorption associated with GSE can lead to deficiencies of B vitamins and folate. Some authors report that both oral and gut lesions resolve with a gluten-free diet. Furthermore, some patients with lesions of RAS may not have symptoms of GSE, but yet the oral lesions will improve with a gluten-free diet16. Thus, patients with RAS may have symptomatic or asymptomatic GSE with gluten hypersensitivity and/or nutritional deficiencies, either or both of which may be related to the development of the lesions of RAS. However, Hunter and co-authors17 report that, in the absence of documented GSE, a double-blind controlled study of patients with RAS did not confirm that a gluten-free diet or a gluten-supplemented diet consistently yielded benefit or worsening for patients, but did show a large placebo effect.

The lesions of RAS may be associated with inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease. Simple or complex aphthosis may antedate, coexist, or serve as a marker for increasing intestinal disease activity. Patients with IBD not only have lesions of RAS but may also have erythema nodosum, papulopustular lesions or lesions of pustular vasculitis, and inflammatory ocular disease such as iritis and uveitis. Thus the distinction between multisystem IBD and BD may be difficult18-21.

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  • Florian
    Do not overdiagnosed complex aphthosis?
    3 years ago

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