Q:

10/30/2012
A 35 yo Caucasian woman was referred to me for eval of chronic stomatitis. Prior w/u in Atlanta by an allergist IgG616, IgG1 312, Dipth/tetanus titers wnl, pneumococcal titers 12of23 poor response (<1.3)buccal bx c/w "suspicious" for autoimmune bullouse disease with HandE stained specimins and direct IF 1+ IgG staining. PMH + celiac disease; 4 dental abcesses in past 12 months, no other non oral infections. CT sinus with minimal mucosal thickening R max but otherwise wnl; repeat IgG and IgG1 still mildly low 631/323 respectively. CH50 nl with low C3 (80), C4 (14), and properdin (17); lyphocyte subset with low CD3+ 747 (840-3060) low CD4+ 431 (490-1740), and low CD19+ 83 (110-660), nl helper supressor ratio (1.35) Negative HIV 1/2 antibodies. ESR 4 , neg ROS for connective tissue disease, renal, or hepatic disease. PE non contrib except somewhat malnourished appearing, oral exam no bullous lesions seen, non-specific aphthous like areas, but visibly painful to patient. Historically she has had these since puberty. Celiac disease manifest primarily with "bloating", not bx proven, repeat TTA negative (but avoids gluten). exam non contrib.

Do you have any suggestions for further work-up/ treatment options (IVIG?). Thanks.

A:

Thank you for your inquiry.

There are actually two syndromes which may be clinically distinct in which recurrent aphthous stomatitis is a problem. One of these, periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome (PFAPA syndrome), was reviewed recently on the “Ask the Expert” website. That review was posted on 5/14/2012, and contains a discussion of this syndrome and its therapy along with a test that might be ordered such as an IgD and evaluation for mevalonate kinase deficiency.

You did not mention whether your patient had fever, pharyngitis, or adenitis associated with the aphthous stomatitis, but if she does, this entry, which can be reached by typing “aphthous stomatitis” in the search box on the Academy Ask the Expert website, would be helpful to you.

I am assuming, however, since you did not mention the other manifestations of this syndrome, your patient has only the recurrent aphthous stomatitis as a manifestation of her condition. In this case such additional workup would not be indicated, and I think, with the exception of a Tzanck smear, you have done a sufficient evaluation. In terms of a Tzanck smear and the workup of a gingivostomatitis patient, you might also find an entry on this condition posted on 3/30/2012 helpful. You may access this entry by typing “recurrent gingivostomatitis” in the search box on our website.

The “bottom line,” however, in terms of looking for an etiology and a specific therapy that is universally effective is that such are rarely found. In most instances, the treatment is prednisone. As you can see from the abstract copied below of the most recent Cochrane Database Systematic Review, there is no specific therapy that fits all patients.

In summary, if your patient does not have PFAPA syndrome, then I think no further workup with the exception of a Tzanck smear would be indicated, and therapy would probably best be done with prednisone. If she does have the accompanying symptoms characteristic of PFAPA syndrome, then the article posted on 5/14/2012 will be helpful to you. However, this syndrome is also treated with prednisone for the most part.

Thank you again for your inquiry and we hope this response is helpful to you.

Cochrane Database Syst Rev. 2012 Sep 12;9:CD005411. doi: 10.1002/14651858.CD005411.pub2.
Systemic interventions for recurrent aphthous stomatitis (mouth ulcers).
Brocklehurst P, Tickle M, Glenny AM, Lewis MA, Pemberton MN, Taylor J, Walsh T, Riley P, Yates JM.
Source
School of Dentistry, The University of Manchester, Manchester, UK.
Background: Recurrent aphthous stomatitis (RAS) is the most frequent form of oral ulceration, characterised by recurrent oral mucosal ulceration in an otherwise healthy individual. At its worst RAS can cause significant difficulties in eating and drinking. Treatment is primarily aimed at pain relief and the promotion of healing to reduce the duration of the disease or reduce the rate of recurrence. A variety of topical and systemic therapies have been utilised.
Objectives: To determine the clinical effect of systemic interventions in the reduction of pain associated with RAS, a reduction in episode duration or frequency.
Search Methods: We undertook electronic searches of: Cochrane Oral Health Group and PaPaS Trials Registers (to 6 June 2012); CENTRAL via The Cochrane Library (to Issue 4, 2012); MEDLINE via OVID (1950 to 6 June 2012); EMBASE via OVID (1980 to 6 June 2012); CINAHL via EBSCO (1980 to 6 June 2012); and AMED via PubMed (1950 to 6 June 2012). We searched reference lists from relevant articles and contacted the authors of eligible trials to identify further trials and obtain additional information.
Selection Criteria: We included randomised controlled trials (RCTs) in which the primary outcome measures assess a reduction of pain associated with RAS, a reduction in episode duration or a reduction in episode frequency. Trials were not restricted by outcome alone. We also included RCTs of a cross-over design.
Data Collection and Analysis: Two review authors independently extracted data in duplicate. We contacted trial authors for details of randomisation, blindness and withdrawals. We carried out risk of bias assessment on six domains. We followed The Cochrane Collaboration statistical guidelines and risk ratio (RR) values were to be calculated using fixed-effect models (if two or three trials in each meta-analysis) or random-effects models (if four or more trials in each meta-analysis).
Main Results: A total of 25 trials were included, 22 of which were placebo controlled and eight made head-to-head comparisons (five trials had more than two treatment arms). Twenty-one different interventions were assessed. The interventions were grouped into two categories: immunomodulatory/anti-inflammatory and uncertain. Only one study was assessed as being at low risk of bias. There was insufficient evidence to support or refute the use of any intervention.
Authors' Conclusions: No single treatment was found to be effective and therefore the results remain inconclusive in regard to the best systemic intervention for RAS. This is likely to reflect the poor methodological rigour of trials, and lack of studies for certain drugs, rather than the true effect of the intervention. It is also recognised that in clinical practice, individual drugs appear to work for individual patients and so the interventions are likely to be complex in nature. In addition, it is acknowledged that systemic interventions are often reserved for those patients who have been unresponsive to topical treatments, and therefore may represent a select group of patients.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology