An Unusual Presentation of Acute Sarcoidosis: Erythema Nodosum, Fever, Arthritis and Normal Chest X-Ray
An Unusual Presentation of Acute Sarcoidosis: Erythema Nodosum, Fever, Arthritis and Normal Chest X-Ray
Lamprini Tina1, Panagiotis Andriopoulos2*, Panagiotis Kourkoulis3, Dimitris Koutoufaris3
1Respiratory Department, Sparta General Hospital, Sparta, Greece
2Faculty of Nursing, University of Peloponnese, Orthias Artemidos & Plataion, Sparta, Greece
3Department of Internal Medicine, Sparta General Hospital, Sparta, Greece
*Corresponding author: Panagiotis Andriopoulos, Faculty of Nursing, University of Peloponnese, Orthias Artemidos & Plataion, Sparta, Greece, E-mail: firstname.lastname@example.org
Citation: Tina L, Andriopoulos P, Kourkoulis P, Koutoufaris D (2015) An Unusual Presentation of Acute Sarcoidosis: Erythema Nodosum, Fever, Arthritis and Normal Chest X-Ray. J Resp Dis 1(1): 101.
A 45 year old woman with an unusual form of acute sarcoidosis is presented. The patient had a week history of fatigue, fever, cough and arthritis and developed erythema nodosum, anterior uveitis and symmetrical ankle arthritis on admission. She had stage 0 radiological findings and normal computerized tomography (CT) scan of the thorax. Sarcoidosis was suspected and diagnosis was based on history, clinical presentation and bronchoalveolar lavage results. Treatment was conservative and all co existent symptoms resolved. Acute sarcoidosis may present in various forms and severity and the clinician must always have in mind that the classic radiographic findings on chest X ray may not be present in all patients.
Keywords: Acute sarcoidosis; Erythema nodosum; Anterior uveitis; Bronchoalveolar lavage
Sarcoidosis is a systemic granulomatous disease of unknown etiology that may involve many tissues and organs in the body. The clinical presentation of sarcoidosis ranges from an incidental chest radiographic finding in an asymptomatic patient to chronic progressive organ dysfunction . The disease usually appears between ages 20 to 50 . The vast majority of patients (> 90%) have some form of pulmonary involvement .
Acute sarcoidosis can present as Lofgren's syndrome with acute erythema nodosum, bilateral hilar lymphadenopathy, fever and polyathritis. Symptoms are typically abrupt in onset and have a transient course . Other features of acute disease can include vesicular or maculopapular rash, anterior uveitis with acute iritis and/or conjunctivitis and Bell's palsy . However, a significant number of patients (< 10%) present only with extrapulmonary manifestations of the disease that may involve any organ . We present here a case report of a patient with fever, arthritis, anterior uveitis and erythema nodosum without any radiologic evidence of the disease.
A 45-year old white woman with no significant medical history presented to the emergency department of our hospital. She reported fatigue, fever up to 38.5 ?C and dry paroxysmal cough during the previous week, pain and swelling in both ankles. She had already received azithromycin 500 mg/day for 3 days with no clinical improvement by her physician who treated her for suspected acute bronchitis. The day prior to her visit to the hospital, she consulted again her physician because her symptoms had not resolved. He then started treatment with montelukast 10 mg once daily, because he suspected that her cough was due to allergic rhinitis. The next day she reported immediate appearance of erythema on anterior surfaces of both legs and came to the hospital.
Clinical examination revealed erythema nodosum skin lesions pretibially. Musculoskeletal system examination revealed synovitis in both ankles. Cardiovascular examination was normal. The patient had no pallor cyanosis or digital clubbing. Physical examination of the chest revealed a bilaterally symmetrical thorax with a respiratory rate of 16 per minute without abnormalities on respiratory movements. There was no pain or swelling on palpation and auscultation revealed bilateral ronchi. Abdominal examination revealed no tenderness, organomegaly or masses. No peripheral adenopathy was noted. Neurological examination was also normal. Her temperature was 39 ?C, with normal blood pressure (120/80 mmHg) and she had 97% spO2 while breathing ambient air. Chest radiography did not show any evidence of lung disease or hilar lymphadenopathy (Table 1). summarizes laboratory results on admission, and on discharge. Apart from C Reactive protein (CRP), Erythocyte Sedimentation Rate (ESR) and a mild elevation of white blood cells all other tests were normal. The patient was admitted in the internal medicine department of our hospital.
Table 1: Basic laboratory results of the patient
After blood and urine cultures, sputum cultures after sputum induction and a tuberculin skin test the patient was treated as a lower respiratory tract infection, with a respiratory fluoroquinolone (moxifloxacin), 400 mg/day and inhaled salbutamol (2.5 mg 3 times daily) and budesonide (250 μgr. twice daily) while montelukast was discontinued. Her fever persisted until the fifth day of hospitalization. Blood and urine cultures remained negative as-well as sputum test for acid fast bacilli and the tuberculin skin test performed on admission. Cardiological, ophthalmological and respiratory consultation was requested. Ophthalmological examination revealed anterior uveitis in the form of iridocyclitis and she received topical corticosteroid drops. Transthoracic ultrasonography was normal and a 24h Holter ECG monitoring revealed no arrhythmias. Respiratory consultation suggested a possible diagnosis of acute sarcoidosis and suggested that vasculitis syndroms and autoimmune disorders such as primary biliary cirrhosis, systemic lupus erythematosus or rheumatoid arthritis should be excluded.
A CT scan of the thorax revealed no abnormalities of lung parenchyma and mediastinum or any lymph node enlargement. Tests for autoimmune diseases imcluding Wegener’s granulomatosis were negative (Table 1). Spirometry test of lung function and bronchoscopy was performed. Table 2 summarizes the lung function tests and the bronchoscopy results. The bronchoalveolar lavage results were suggestive of the presence of granulomatous disease.
Table 2: Presents the spirometry and bronchoscopy results. The patient was on bronchodilators and inhaled corticosteroids during her hospital stay, the results are post bronchodilation. BAL was suggestive of granulomatous disease .
The erythema nodosum and arthritis symptoms gradually resolved. The patient improved and left the hospital with no arthritis or erythema nodosum after 10 days of hospitalization on inhaled corticosteroids. Sputum cultures were negative for common pathogens and eventually mycobacteria. Her cough had almost disappeared one month after initial presentation. Three months later ophthalmological examination was normal and steroid drops were discontinued. Six months later in a follow up visit she was free of symptoms with normal pulmonary function tests, chest x ray, ECG and blood tests. She is followed up on a six month schedule by the hospital’s respiratory department and remains well ever since.
Sarcoidosis is a multisystem disease of unknown etiology that may affect any organ or system in the body and is characterized by non caseating (non-necrotizing) granulomas on biopsy . The biopsy results together with chest radiographic evidence and compatible clinical features are necessary to establish the diagnosis when all other causes of granulomas have been ruled out . Histological confirmation is not needed for Lofgren's syndrome or asymptomatic bihilar lymphadenopathy . Sarcoidosis is often a diagnosis of exclusion when no definitive imaging study or diagnostic test is available .
Pulmonary involvement may include symptoms as cough, shortness of breath and/or chest pain. The lung examination can be normal or reveals crackles and/or wheezing. Patients may have normal lung function, even with radiographic abnormalities, or may demonstrate obstruction, restriction, abnormal gas exchange or a combination of these . The most frequent abnormalities found are reductions in vital and diffusing capacity, suggesting a restrictive pathophysiology, although airflow limitation is also reported as a common defect . The radiologic patterns in sarcoidosis are classically described by Scadding staging (0-IV) based on the chest radiography. They do not correspond to chronologic progression of disease, but correlate to future symptomatic and radiographic resolution. Stage 0 is seen in 5% - 10% of patients at presentation. Stage 0 disease has a low likelihood to disease progression . Definite diagnosis of intrathoracic involvement requires biopsy. The procedure of choice in most cases is transbrochial biopsy that yields diagnosis in 40 - 90% depending on operator experience, the number of biopsies taken and the Scadding stage . Bronchoalveolar lavage (BAL) lymphocyte differential count > 25% suggests granulomatous diseases while a CD4+/CD8+ > 4 is highly specific for sarcoidosis in the absence of an increased proportion of other inflammatory cell types [13,14]. Our patient did not have any evidence of lung involvement in order to proceed to biopsy and the decision for a bronchoscopy was based on the other clinical features of her disease.
The patient had erythema nodosum. Erythema nodosum is an acute inflammatory dermatosis characterized by painful nodules which are generally symmetrical and non ulcerative and are mainly located to the extensor surface of the lower legs. The nodules, due to septal panniculitis, are often accompanied by fever and resolve without permanent sequelae . Arthralgia occurs in more than 50% of patients and begins during the eruptive phase or precedes the eruption by 2-4 weeks. Erythema nodosum is presumed to be a hypersensitivity reaction and may appear in the clinical course of several systemic diseases and drug therapies, or may be idiopathic. Peak incidence occurs at age 18-34 years. Age and sex distributions vary according to etiology and race; women are affected more often than men. Twenty five percent of sarcoidosis patients present with erythema nodosum on diagnosis. These patients are more likely to be young females with early stage radiological disease [16,17].
Our patient also had anterior uveitis, which is the most common manifestation in sarcoidosis, accounting for 65% of all ophthalmologic involvement of the disease . Uveitis may precede the non ocular signs of sarcoidosis in 30% of the patients while more than 80% of uveitis cases manifest before or within one year after the onset of systemic disease [19,20]. Conjunctival biopsy may be performed to establish the diagnosis but it is not routinely recommended . Topical corticosteroids are used as treatment, while systemic administration is necessary in patients with optic neuritis and resistant posterior uveitis . Our patient’s symptoms resolved with application of topical agents.
Finally our patient presented with arthritis of both ankle joints. Arthritis in sarcoidosis is well documented in the literature  and is very common in the acute form of the disease (Lofgren’s syndrome) . Visser et al.  describe acute sarcoid arthritis as a cluster of four clinical features: symmetrical ankle arthritis, symptoms of less than two months, age below 40 years, and erythema nodosum. Also in most cases, acute sarcoid arthritis is self-limited with minimal or no joint destruction .
Presentation of sarcoidosis without apparent lung involvement on x-ray or CT is not a common presentation of sarcoidosis. Bauhman et al.  in a large case series reported 95% lung involvement (699/734 patients) but with 8.3% (61/734) stage 0 x-ray. Recent guidelines suggest that in patients with no apparent lung involvement 18F-fluorodeoxyglucose positron-emission tomography (18FDG PET) is useful in identifying sites for diagnostic biopsy . However, the cost and availability of PET scan is a drawback to implement the test in everyday practice and the clinical course of our patient did not mandate such a procedure. In any case biopsy is not routinely recommended for patients with Lofgren’s syndrome and for the other alternative site of biopsy in our patient, the conjunctiva, the positive rate of patients with pathologic findings suggesting sarcoidosis in conjunctival biopsy ranges from 38 to 55% . Since in some patients BAL can be used for diagnosis  no biopsy was performed.
Differential diagnosis of sarcoidosis includes infectious diseases (predominantly tuberculosis), occupational disorders such as berylliosis, drug induced granulomatosis (anti TNFa, interferon a and b etc.), proliferative disorders (lymphomas and solid neoplasias) and autoimmune diseases such as Wegener’s granulomatosis, Crohn’s disease and primary biliary cirrhosis . Our patient did not have any history of occupational hazard or use of any such drugs. Immunological essays were negative and no tumor was identified. Tuberculosis is always a puzzle however negative sputum smears and cultures, negative tuberculin test and no other symptoms of infection ruled out the diagnosis.
It is not known why some patients recover and others progress. Even after an apparent recovery, a proportion of patients may relapse months to years later. Factors associated with worst prognosis include older age at the time of diagnosis, African American race, pulmonary infiltrates, splenomegaly, lupus pernio, the number of organs involved and duration of sarcoidosis more than six months .
Treatment of most patients with Lofgren's syndrome requires only short term bed-rest and nonsteroidal anti-inflammatory drugs. These patients have an excellent prognosis . Most patients do not require treatment . The use of oral corticosteroids for the cough of patients has been described in the literature . Monitoring of pulmonary function tests, blood test including serum creatinine and calcium, ECG and x-ray are recommended for follow up of patients with sarcoidosis together with ophthalmological consultation for recurrent uveitis . Our patient is on follow up and free of symptoms and findings .
In conclusion we report an acute presentation of a patient with sarcoidosis presenting with erythema nodosum, fever, anterior uveitis and arthritis but with stage 0 radiological presentation. The treatment was conservative and all coexistent symptoms resolved. The patient is on routine follow up in an outpatient basis.
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