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Oral Manifestations of a Possible New Periodic Fever Syndrome Soraya Beiraghi, DDS, MSD, MS, MSD1 • Sandra L

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Oral Manifestations of a Possible New Periodic Fever Syndrome Soraya Beiraghi, DDS, MSD, MS, MSD1 • Sandra L PEDIATRIC DENTISTRY V 29 / NO 4 JUL / AUG 07 Case Report Oral Manifestations of a Possible New Periodic Fever Syndrome Soraya Beiraghi, DDS, MSD, MS, MSD1 • Sandra L. Myers, DMD2 • Warren E. Regelmann, MD3 • Scott Baker, MD, MS4 Abstract: Periodic fever syndrome is composed of a group of disorders that present with recurrent predictable episodes of fever, which may be accompanied by: (1) lymphadenopathy; (2) malaise; (3) gastrointestinal disturbances; (4) arthralgia; (5) stomatitis; and (6) skin lesions. These signs and symptoms occur in distinct intervals every 4 to 6 weeks and resolve without any residual effect, and the patient remains healthy between attacks. The evaluation must exclude: (1) infections; (2) neoplasms; and (3) autoimmune conditions. The purpose of this paper is to report the case of a 4½- year-old white female who presented with a history of periodic fevers accompanied by: (1) joint pain; (2) skin lesions; (3) rhinitis; (4) vomiting; (5) diarrhea; and (6) an unusual asymptomatic, marked, fi ery red glossitis with features evolving to resemble geographic tongue and then resolving completely between episodes. This may represent the fi rst known reported case in the literature of a periodic fever syndrome presenting with such unusual recurring oral fi ndings. (Pediatr Dent 2007;29:323-6) KEYWORDS: PERIODIC FEVER, MOUTH LESIONS, GEOGRAPHIC TONGUE, STOMATITIS The diagnosis of periodic fever syndrome is often challeng- low, mildly painful ulcerations, which vary in number, and ing in children. Periodic fever syndrome is composed of a resolve completely along with other signs and symptoms. heterogeneous group of often hereditary disorders, charac- Aphthous ulcerations also occur in CN and may progress in terized by recurrent fevers in otherwise healthy individuals.1 size to become deep and painful.3 Major aphthae (periadeni- Recurrent infections or neoplasms, along with known auto- tis mucosa necrotica recurrens or Sutton’s disease), gingi- immune disorders, must be ruled out as possible underlying vitis and periodontal involvement have been reported with causes. There are 5 main types of periodic fever syndromes CN.3 Aphthous ulcers have been observed in a minority of reported in children that have been identifi ed based on hyper Ig-D cases, but oral lesions have not been reported as a their clinical presentations: (1) periodic fever, aphthous sto- signifi cant fi nding in either FMF or TRAPS. Tongue lesions, matitis, pharygitis and cervical lymphadenopathy (PFAPA); other than aphthous ulcers, have not been documented as a (2) cyclic neutropenia (CN); (3) hypergammaglobulinemia signifi cant fi nding in any periodic fever syndrome. The pur- D (hyper-IgD); (4) familial Mediterranean fever (FMF); and pose of this report was to describe a case of periodic fever (5) tumor necrosis factor receptor-associated periodic fever syndrome in a child with a symptomatic, recurrent, fi ery red (TRAPS). Main clinical features of these conditions are sum- glossitis, which evolved to resemble geographic tongue and marized in Table 1. then resolved completely between episodes. Oral conditions reported in patients with the periodic fever syndromes previously described include: (1) oral ulcer- Case description ations; (2) gingivitis; and (3) periodontal destruction. Intra- A 4½-year-old, well-nourished Caucasian girl was referred oral aphthous ulcers are a hallmark of PFAPA and present in to the Pediatric Dental Clinic of the University of Minnesota, up to 68% of cases.2 These are generally minor, small, shal- Minneapolis, Minn, for evaluation of an unusual recurrent asymptomatic glossitis. The patient’s medical history re- vealed the presence of periodic fevers, occurring at regular 3½ to 4½ week intervals, always with an asthma exacerba- 1Dr. Beiraghi is professor, Department of Developmental and Surgical Science, and head, Division of Pediatric Dentistry, 2Dr. Myers is associate professor and Director of the Na- tion. Clinical signs and symptoms included: (1) arthralgia in tional Institute of Dental and Craniofacial Research’s Temporomandibular Joint Im- the hands and knees; and (2) a fever of 101°F to 104°F lasting plant Registry and Repository (TIRR) Laboratory, Department of Diagnostic and Biologi- for 2 to 3 days. 3 cal Sciences, Dr. Regelmann is associate professor, Department of Pediatrics, Division of Signifi cant intraoral fi ndings included a fi ery red glos- Pediatric Pulmonology and Infectious Diseases, and 4Dr. Baker is associate professor, Department of Pediatrics, Division of Hematology-Oncology and Blood and Marrow Transplant, all at the University of Minnesota School of Medicine, Minneapolis, Minn. Correspond with Dr. Beiraghi at [email protected] PERIODIC FEVER SYNDROME 323 PEDIATRIC DENTISTRY V 29 / NO 4 JUL / AUG 07 Table 1. PERIODIC FEVER SYNDROME DIFFERENTIAL DIAGNOSIS Periodic fever, Familial Tumor Necrosis Clinical Aphthous stomatitis, Cyclic Hypergammaglobulinemia Mediterranean Factor Receptor- Presentation Pharyngitis, and Neutropenia D Fever Associated Periodic Fever Cervical Adenopathy Age of Onset <5 <1 <1 <10 <1 (years) Abdominal Pain X X Amyloidosis X X Aphthous X X Stomatitis Arthralgia/ X X X Arthritis Cervical X X X Lymphadenopathy Chills X Conjunctivitis X Diarrhea X Elevated IgD/IgA * X Elevated ESR † X Hereditary X X X X Malaise X Mild X Leukocytosis Myalgia X X Oral Ulcers X X Pericarditis X Periodic X Neutropenia Periodicity <4 weeks 21 days Variable ? Variable Periorbital X Edema Peritonitis X Pharyngitis X X Pleuritis X Rash X Serositis X Skin lesions X X Vomiting X Therapy Prednisone RG-CSF ‡ None Colchicine Prednisone * IgD/IgA: Immunoglobulin D/ Immunoglobulin A † ESR: erythrocyte sedimentation rate ‡ recombinant granulocyte colony stimulating factor 324 PERIODIC FEVER SYNDROME PEDIATRIC DENTISTRY V 29 / NO 4 JUL / AUG 07 sitis, which over time evolved to resemble geographic tongue fever conditions described. PFAPA was ruled out, since the and then resolved between episodes (Figures 1-3). Phar- patient did not exhibit aphthous ulcerations or signifi cant yngitis and signifi cant lymphadenopathy were not present. cervical lymphadenopathy. Cyclic neutropenia was a consid- Unusual red cutaneous lesions with crusting were present on eration because of the unconfi rmed family history of neutro- the face, arms and nose. The child was the second-born (41 penia in a maternal uncle. weeks gestation) to nonconsanguineous parents. Prenatal, Repeated laboratory testing, however, did not confi rm perinatal, and postnatal histories were unremarkable, and all the presence of neutropenia, and the patient did not exhibit developmental milestones were within normal ranges. The destructive oral ulcerations or repeated severe infections. Hy- patient was hospitalized at age 1½ years for vomiting/diarrhea per-IgD was considered but laboratory testing never indicated and resultant dehydration. She was hospitalized twice for re- sustained high levels of IgD. The skin lesions did not resemble spiratory syncytial virus (RSV) at ages 2½ and 3½ years. the erythematous papules, which may be seen in hyper-IgD Figure 1. Fiery red glossitis Figure 2. Geographic tongue appearance Figure 3. Appearance of tongue between episodes In 2002, the patient was hospitalized for respiratory distress disease. FMF and TRAPS exhibit less clock-like periodicity with tachypnea and a diagnosis of acute exacerbation of severe than this case and do not have recurrent oral manifestations. persistent asthma. She required intubation and mechani- Skin lesions, which are erysipelas-like in FMF, and in TRAPS cal ventilation and remained hospitalized for 10 days. The occur as a rash which migrates distally, were not present. In patient’s asthma was subsequently controlled with albuterol addition, none of the main periodic fever syndromes identi- and a fl uticasone 220 mcg/discharge inhaler (2 puff s twice fi ed presented with a recurrent glossitis. Her eosinophilia, daily). The family history was signifi cant for asthma (mother increased IgE, increased specifi c IgE, and asthma are sug- and maternal uncle). A maternal fi rst cousin’s daughter had gestive of Churg-Strauss angiitis. The glossitis progressing a low level of IgA, IgE, and IgG. In addition, a paternal uncle to geographic tongue, however, has not been described in this reported frequent colds and infections as a youth. A maternal disease, and she did not have elevated sedimentation rate.6 uncle has a diagnosis of neutropenia (not cyclic) as a child, Glossitis in children may result from a host of local as and the maternal grandfather has reactive airways disease. well as systemic factors. Some local factors include trauma All laboratory results, including repeated neutrophil counts, due to injury or burns, sensitivities to foods, topical medi- erythrocyte sedimentation rate, IgA, IgG, IgM, and IgD, were cations, or oral hygiene products such as toothpastes and normal. The patient had slightly increased eosinophil counts mouthwashes.7 Infections such as candidiasis or primary (13%). Total IgE was increased (514 mg/dl), as was the IgE herpetic gingivostomatitis may also produce a pronounced specifi c for dog, cat dander, and dust mites. stomatitis and glossitis. Glossitis due to these local factors is most often symptomatic and transitory, and there is com- Discussion plete resolution without repeating episodes. More persistent Pediatric patients with periodic fevers of unknown origin can forms of glossitis occur with systemic conditions, such as: (1) present a diagnostic challenge for clinicians.4,5 This
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