It's Not So Sweet

Carol Rudy, MPH, ARNP, CPNP

J Pediatr Health Care. 2008;22(6):387-389. 

Introduction

Sixteen-year-old Lucy initially was seen in mid October with symptoms of fatigue, anorexia, and upper respiratory symptoms including a sore throat. Results of laboratory tests, including a complete blood cell count (CBC), were unremarkable, and a mononucleosis screen and throat culture were negative. She returned 2 weeks later and had been in bed since she was last seen with increasing symptoms of fever, headache, total body aches, and 5 days of dysphagia. She had noted a lesion on her labia that day. She denied urinary frequency, urgency, and dysuria and stated unequivocally that she was not sexually active. Lucy has been an excellent student and normally is very active in school sports and extracurricular activities. On examination she appeared to be ill, was adequately hydrated, and was significantly fatigued. Her examination was within normal limits with the exception of shotty bilateral anterior cervical and inguinal nodes and a small, approximately one-half centimeter, eroded lesion on the left labia majora. A mononucleosis screen and bacterial and viral cultures of the labial lesions were negative. A CBC, Epstein-Barr virus screen, and immunoglobulin G and A were within reference range. Her bacterial culture of the labial lesion was negative for any growth.

Her medical history was noncontributory. She was taking no regular medications and had no known drug allergies. She lives with both parents and a sister and is a junior at a private high school. Her family history reveals no history of rheumatologic disease, and her grandmother had breast cancer.

Her progress was followed closely by telephone contact, and her symptoms cleared after approximately 5 weeks. She did well for about 3 weeks; then a fever up to 104°F developed, along with night sweats, myalgias, arthralgias, and multiple blister-type lesions on her labia. She had no oral ulcers.

She was hospitalized and underwent an extensive evaluation, including computed tomography (CT) scans of her abdomen and pelvis, which were normal. Her rheumatologic workup included a normal antinuclear antibody, rheumatoid factor, and Complement 3 and 4. A colonoscopy showed no sign of inflammatory bowel disease. Her labial lesions were biopsied and found to be consistent with Sweet's syndrome or acute febrile neutrophilic dermatosis, a skin disorder characterized by fever and painful skin lesions that occurs most frequently in women 30 to 50 years of age (Sweet's Syndrome, 2006). Lucy was treated with a tapering dose of steroids and did well. All her symptoms resolved following her steroid course.

Two weeks later a cough and sore throat developed, which was thought by her primary care provider to be due to influenza, even though an influenza test was negative. Tamiflu was prescribed. She began having fevers and night sweats and a new labial lesion developed, which was extremely painful. She described her throat as hurting very low in her neck, feeling different than most sore throats. She again was admitted to the hospital because of concerns that the Sweet's syndrome could be a marker of lymphoma. A pediatric oncology consult was done.

Her admission examination showed some weight loss, a 1-cm erosive lesion at the base of the vulva, and a small punctate lesion on the right mid labia. Results of her examination were otherwise normal. Findings of laboratory tests included a normal CBC and differential, an erythrocyte sedimentation rate of 6 mm/hour, and an elevated C-reactive protein of 4.1 mg/L. CT scans of her neck, chest, abdomen, and pelvis were done to rule out adenopathy that might be associated with lymphoma and showed a subglottic soft tissue density compatible with secretions, a right upper lobe infiltrate, and a small amount of free fluid in the right pelvis. After admission, Cefotaxime and subsequently Indomethacin were prescribed, and she had marked improvement, with regression of her labial lesions and improved appetite.

A rheumatology consult was obtained, and the diagnosis remained Sweet's syndrome/acute febrile neutrophilic dermatosis. She had no occult malignancy associated with Sweet's syndrome, nor did she have any other rheumatologic disorders such as inflammatory bowel disease, systemic lupus erythematosus, Sjögren's syndrome, or rheumatoid arthritis. Lucy was referred to a pediatric rheumatologist at a tertiary children's hospital where her diagnosis was changed.

Case Study Questions

  1. What was her new diagnosis?

  2. What is the etiology of this disease?

  3. How is the diagnosis made?

  4. What is the treatment?

  5. What is Lucy's prognosis?

Case Study Answers

Her final diagnosis was Behcet's disease. "Behcet's disease is a systemic vasculitis characterized by recurrent oral and genital ulcers, and ocular inflammation, and which may involve the joints, skin, central nervous system and gastrointestinal tract" (Marshall, 2004, p. 291). A multicenter study of 661 patients showed that nearly 100% had oral ulcers, which is considered the sine qua non of Behcet's disease, and may precede the onset of systemic symptoms by many years. Genital ulcers are the second most common manifestation, occurring in approximately 85% of the patients, and are morphologically similar to the oral lesions but frequently scar when they heal (Alpsoy et al., 2007; Marshall). Ocular involvement will develop in 30% to 70% of patients, with an increased frequency and severity in men (Marshall). Additional manifestations include skin disease such as erythema nodosum, joint symptoms including synovitis, arthritis, or arthralgias, vascular disease, and a wide spectrum of gastrointestinal symptoms such as anorexia, vomiting, dyspepsia, diarrhea, and abdominal pain. Central nervous system involvement is less common, occurring in 5% to 10% of patients, but it carries a 5% to 10% mortality rate. Constitutional symptoms such as fatigue, malaise with or without fever, and weight loss are common.

One of the reasons it was so difficult to determine Lucy's diagnosis is because Behcet's disease is uncommon in children. When it does occur it affects boys and girls equally, and there is frequently a family history of disease. Symptoms in children are similar to those of adult-onset disease; however, children are more likely to have recurrent episodes of fever (Marshall, 2004).

The etiology is unknown, but current thought suggests a significant inflammatory response triggered by an infectious agent in a genetically susceptible host. Familial cases are not very common, with the highest incidence of the disease occurring along the so called "Silk Road" countries of the Mediterranean, Middle East, and Far East. The incidence is less in Western Europe and North America (Reynolds, 2008).

There is no specific test for Behcet's disease, and all of its symptoms have other possible causes. Diagnosis is based on clinical criteria, and in 1990, several classifications were amalgamated into the International Study Group Classification criteria. These criteria were developed primarily to be used in research programs; however, they also work well in the clinical setting. These diagnostic criteria require the presence of oral ulcerations plus any two of the following symptoms: genital ulceration, typical defined eye lesions, typical defined skin lesions, or a positive pathergy test (Wechsler et al., 1990).

Pathergy, one of the major criteria of the disease, is a nonspecific hyper-reactivity to minor trauma such as a needle prick and is the only specific feature of Behcet's disease. Krause and Weinberger (2008) reported that while the pathergy reaction was not found to occur in healthy control subjects, it did occur in 85.7% of patients with Behcet's disease and in 18% of patients with recurrent aphthous stomatitis. There is no standardized method of measuring pathergy (Krause & Weinberger).

The great variability in the expression of clinical and genetic manifestations in different ethnic groups and geographic locations, as well as absent symptoms of oral and genital ulcers, make early diagnosis difficult. Based on the multiple symptoms, a detailed evaluation is necessary to exclude other conditions and reveal subtle features of this complex disease (Marshall, 2004).

Laboratory results are nonspecific in Behcet's disease. Fifteen percent of patients have a neutrophil leukocytosis, and moderate anemia is common. Other laboratory results including nonspecific markers of inflammation such as C-reactive protein and erythrocyte sedimentation rate frequently are normal despite the presence of active oral or genital lesions or ocular or central nervous system disease.

Research is ongoing; however, because there is no standardized treatment protocol, current treatment is empirical and varies significantly between treatment centers. The primary goal is to control symptoms, suppress inflammation early, and prevent end-organ damage using anti-inflammatory agents and immunosuppressants. Acute exacerbations frequently are managed with intravenously administered corticosteroids. Long-term use of oral steroids is avoided if possible because of the incidence of significant adverse effects. Numerous immunosuppressants have been used, with Cyclosporine frequently the mainstay in cases of severe disease (Marshall, 2004).

The clinical course of Behcet's disease is highly variable and includes relapses and remissions. It is usually more severe in individuals of Mediterranean and Eastern descent when compared with Western populations, and it is usually more severe in males versus females. Studies indicate that mortality rates decrease over time and the prognosis improves after the initial years, supporting the need for early diagnosis and appropriate treatment. Blindness and neurologic disease are the major causes of permanent disability (Marshall, 2004). As with any chronic illness, there is a significant risk of major depression developing.

Lucy is a white female adolescent whose disease was diagnosed within 5 to 6 months of the development of symptoms. It is hoped that her prognosis will be favorable. The case study format allows for a brief overview of this uncommon disease. Additional information can be obtained from the sources listed.

References

  1. Alpsoy E, Donmez L, Onder M, Gunasti S, Usta A, Karincaoglu Y, et al. Clinical features and natural course of Behcet's disease in 661 cases: A multicentre study. British Journal of Dermatology. 2007;157:901-906.

  2. Krause I, Weinberger A. Systemic disorders with rheumatic manifestations. Current Opinion in Rheumatology. 2008;20:82-87.

  3. Marshall S. Behcet's disease. Best Practice and Research Clinical Rheumatology. 2004;18:291-311.

  4. Reynolds N. Vasculitis In Behcet's syndrome: Evidence-based review. Current Opinion in Rheumatology. 2008;20:347-352.

  5. Sweet's Syndrome. (June 19, 2006). Retrieved June 10, 2008, from www.MayoClinic.com.

  6. Wechsler B, Davatichi F, Mizushima Y, Hamza M, Dilsen N, Kansu E, et al. Criteria for diagnosis of Behcet's disease. Lancet. 1990;335:1078-1080.