DOI: 10.1111/pde.
14003
BRIEF REPORT
Severe recurrent aphthous stomatitis treated with adalimumab:
A case report in a teenage patient
Abstract
Recurrent aphthous stomatitis (RAS) is a chronic disorder of un‐
known etiology characterized by recurring ulcers involving the oral
mucosa in patients with no other manifestations. It is a common
cause of oral ulcers in children. In its major form, RAS can be a severe
and disabling disorder due to pain and scarring, and poses a thera‐
peutic challenge. Therapies for major RAS include prednisone, tha‐
lidomide, colchicine, and dapsone. However, many patients do not
achieve adequate control of the disease with them (J Clin Diagn Res,
10, 2016 and ZE08). We report a case of severe RAS in a teenager
with a dramatic response to adalimumab.
1 |  C A S E R E P O RT
A 5‐year‐old male with no remarkable personal or familial history
was seen because of recurrent attacks of painful, deep, round ul‐
cers in the tongue, 1‐3 cm in size. He had no genital ulcers, fever, or
systemic symptoms.1 Complementary tests were normal, including
hemogram, serum chemistry, extensive endocrine laboratory test‐
ing, serum vitamin levels, immunologic studies, and viral serologies.
A genetic panel for monogenic autoinflammatory diseases showed
no pathogenic variant. A biopsy specimen showed non‐specific
mucosal ulceration, with negative direct immunofluorescence. The
F I G U R E 1   Large ulcers and erosions with fibrinous base and
erythematous border on the tongue, after treatment with oral
corticosteroids and colchicine for 3 mo
Pediatric Dermatology. 2019;00:1–2. © 2019 Wiley Periodicals, Inc. |  1
wileyonlinelibrary.com/journal/pde
Pediatric
Dermatology
patient received several cycles of oral corticosteroids and sustained
oral colchicine, achieving satisfactory control of the lesions. Twelve
years later, at the age of 17, he presented with an intense attack of
large, painful ulcers on the tongue, with severe dysphagia (Figure 1).
Oral prednisone 1 mg/kg/day and colchicine were reintroduced for
3 months, without clinical control. Treatment with adalimumab was
begun, with an induction dose of 80 mg subcutaneously and sub‐
sequently 40 mg every two weeks. Six weeks after initiating treat‐
ment, all active lesions had cleared up, and the patient remains free
of aphthae after 12 months of follow‐up with adalimumab therapy.
No adverse effects from treatment have been observed; however,
the tongue has severe residual scarring. (Figure 2).
2 | D I S CU S S I O N
A role for cell‐mediated immune response with a production of vari‐
ous cytokines, including tumor necrosis factor‐α (TNF‐α), has been
suggested in RAS. 2 Increased expression of TNF‐α has been ob‐
served in saliva and serum of RAS patients compared with healthy
F I G U R E 2   The patient after treatment with adalimumab.
Scarring remains, but no active aphthous ulcers
 
 |
2       Pediatric BRIEF REPORT
Dermatology
1
controls. These levels are higher in major RAS compared with the Department of Dermatology, Hospital Universitario Ramón y Cajal,
3
minor form and decrease outside of recurrences. Adalimumab is Madrid, Spain
2
a recombinant human IgG1 monoclonal antibody against TNF‐α. Department of Dermatology, Hospital Infantil Universitario Niño Jesús,
Among its pediatric indications are juvenile idiopathic arthritis, pso‐ Madrid, Spain
riasis, Crohn's disease, and hidradenitis suppurativa.4 Possible side
effects include infections, tuberculosis reactivation, and reaction at Correspondence
injection site. However, these adverse effects are milder than the Darío de Perosanz‐Lobo, MD, Resident of dermatology at Hospital
observed with other anti‐TNF‐α such as etanercept or infliximab. Ramón y Cajal, Carretera de Colmenar Viejo km 9, 100, 28034 Madrid.
Several adult patients with recalcitrant RAS have been success‐ Email: dario.perosanz@gmail.com
1,2
fully treated with TNF‐α inhibitors. The observed response is
rapid, within 2‐6 weeks, and maintained over time. To our knowl‐
ORCID
edge, there are no children with major RAS treated with anti‐TNF‐α
therapy, although children with aphthous stomatitis associated with Dario de Perosanz‐Lobo  https://orcid.
certain systemic diseases (eg, Crohn's disease, Behçet disease) have org/0000-0003-1857-5964
shown good responses.1,5 Irene Latour  https://orcid.org/0000-0002-5669-2283

Antonio Torrelo  https://orcid.org/0000-0002-5940-6916

3 |  CO N C LU S I O N
REFERENCES
Anti‐TNF therapy should be considered as a valid therapeutic option
1. Ranganath SP, Pai A. Is optimal management of recurrent aph‐
on the treatment of recalcitrant RAS. Treatment should be promptly
thous stomatitis possible? A reality check. J Clin Diagn Res JCDR.
established in severe cases to avoid invalidating scars. However, fur‐ 2016;10:ZE08‐ZE13.
ther experiences are required to evaluate the efficacy and safety in 2. Sánchez‐Cano D, Callejas‐Rubio JL, Ruiz‐Villaverde R, Ortego‐
the pediatric population. Centeno N. Recalcitrant, recurrent aphthous stomatitis success‐
fully treated with adalimumab. J Eur Acad Dermatol Venereol JEADV.
2009;23:206.
KEYWORDS 3. Hegde S, Ajila V, Babu S, et al. Evaluation of salivary tumour necrosis
adalimumab, anti‐TNF, aphthous stomatitis, RAS, TNF‐α factor–alpha in patients with recurrent aphthous stomatitis. Eur Oral
Res. 2019;52:157‐161.
4. Poddighe D, Romano M, Gattinara M, Gerloni V. Biologics for
Dario de Perosanz‐Lobo MD1
the treatment of juvenile idiopathic arthritis. Curr Med Chem.
Irene Latour MD2 2019;25(42):5860‐5893.
Daniel Ortega‐Quijano MD1 5. Poddighe D, Mukusheva Z, Dauyey K, Assylbekova M. Adalimumab
Montserrat Fernández‐Guarino MD, PhD1 in the treatment of pediatric Behçet’s disease: case‐based review.
Rheumatol Int. 2019;3:1107‐1112.
Antonio Torrelo MD, PhD2