ZESPÓŁ CHURG-STRAUSSA: OPIS PRZYPADKU
Vyacheslav М. Zhdan, Yevdokiia М. Kitura, Oksana Ye. Kitura, Maryna Yu. Babanina, Maksym V. Tkachenko, Volodymyr G. Lebid
higher state educational establishment of Ukraine “ukrainian medical stomatological academy”, POLTAVA, UKRAINE
A clinical case of Churg-Strauss syndrome has been reported on the 53-year-old female patient Ts. with bronchial asthma and allergic rhinitis. The main clinical signs and syndromes depending on the stage of the disease are presented, as well as therapeutic treatment of patients with this disease.
Wiad Lek 2017, 70, 5, 992-994
Churg-Strauss syndrome (CSS) is granulomatous eosinophilic inflammation of the respiratory tract and necrotizing vasculitis of small and medium vessels, frequently associated with bronchial asthma and eosinophilia . CSS is an autoimmune disease, characterized by hypereosinophilia, sustained by elevated level of interleukin-5 (IL-5) and Т-В- lymphocytes. The prevalence of CSS constitutes 10,7-14 cases per 1 million people, and the annual incidence is 0,5-6,8 of the new case. Churg-Strauss syndrome was first described in 1951 by J.Churg and L. Strauss, who presented the cases of necrotizing vasculitis in patients with severe bronchial asthma, fever and eosinophilia . Antineutrophil cytoplasmic antibodies (ANCA) and especially antibodies to myeloperoxidase were found in this syndrome. Presence of bronchial asthma, eosinophilia and elevated level of eosinophils in tissues is specific to CSS that differentiates it from other systemic vasculitides.
The prevalence of CSS is 10,7-14 cases per 1 million of population, the annual incidence is 0,5-6,8 of the new case; it can develop both in children and adults, and the peak of incidence falls between the ages of 35-50 years.
The etiology of Churg-Strauss syndrome is still unknown. Vaccination, medications, including agonists of leukotriene receptors, used in the treatment of patients with bronchial asthma and antimonoclonal antibodies (Omalizumab); bacterial or viral infection, excessive exposure to cold, pregnancy and childbirth can be the triggering events. The clinical case of progression of the diseases has been described after introduction of macrolides and Chinidinum . CSS is an autoimmune disease, characterized by hypereosinophilia, sustained by elevated level of interleukin-5 (IL-5) and Т-В- lymphocytes. Vasculitis, proliferation of eosinophils, granulomatosis causes deterioration of the general condition.
The 53-year-old female patient Ts. has been admitted to Rheumatological Unit with complaints on the recurrent pain in knee joints, shortness of breath during physical activity, dry coughing, attacks of asphyxiation, a sense of numbness and goose-flesh, weakness in the lower extremities, nausea, heartburn, and abdominal distention. From the past medical history it is known that she has been suffering from allergic rhinitis for 10 years, followed up with dyspnea, cough, recurrent “whistling” in the chest. Urticaria-like skin lesions occured several times. In 2016 she was diagnosed with bronchial asthma. Physical examination demonstrated satisfactory general condition and deformation of knee joints. Respiratory rate was 18 breaths per minute; vesicular harsh breathing with prolonged exhalation, wheezes. Heart rate was 90 beats per minute; blood pressure: 140/80 mm Hg. Tones were weakened and rhythmic. The abdomen was soft, painful in the epigastric area and right upper quadrant; the liver and the spleen was not enlarged.
Complete blood count: Red Blood Cell (RBC):3,61×1012/l; Hemoglobin (НB): 106 g/l; Erythrocyte Sedimentation Rate (ESR): 33 mm/h; Eosinophil (Eos): 72%; Stab n.: 5%, Segment. n.: 15%; Lymphocyte (Lymph): 7%; Monocyte (Mono): 1%.
Urinalysis test: within normal; CRP:12 ml/l; ALT – 30 mmol/l; AST:16 mmol/l; Creatinine: 68 micromol/l; Fibrinogen: 3,0 g/l; ANCA content: 0,73 U/ml (N< 1,0).
Chest computed tomography showe lung fields without changes, the compressed roots of the lung with emphysema-like alterations. Lymphadenopathy was not expressed. The heart was normal. Conclusion: the signs of chronic bronchitis. Spirography demonstrated obstructive-like impairment of the functions of the external respiration.
Ultrasound examination of the abdominal cavity revealed the signs of chronic cholecystitis.
ECG showed sinus rhythm, heart rate was 64 beats per minute, accelerated AV-conductivity (CLC-phenomenon ). Echo cardioscopy demonstrated regular size of the heart; the aorta was moderately compressed without dilatation. Contractility was preserved (EF 69%); relaxation process was impaired. Esophagogastroduodenoscopy demonstrated erythematous gastropathy, gastroesophageal reflux disease. No pathology was found on colonoscopy (60 cm) and irrigoradioscopy.
Myelogram revealed cellular bone marrow with increased number of eosinophilic leucocytes in the myeloblastic process. Hematologist’s consultation showed eosinophilic leukemoid reaction.
Neurologist’s report revealed osteochondrosis of the spine with severe pain syndrome.
ENT’s consultation showed allergic rhinitis.
Pulmonologist’s consultation showed moderate persistent bronchial asthma; controlled phase of remission (eosinophilic).
Diagnostic concept of eosinophilia (swellings, allergy, helminthic invasion, lymphoproliferative disorders, etc.) has been discussed. After thorough examination other causes of eosinophilia were gradually being excluded. On the basis of the analysis of the progress of the disease, results of additional methods of examination the clinical diagnosis was made: systemic granulomatous vasculitis (Churg-Strauss syndrome (CSS)), chronic course, the second stage with the lesions of vessels (syndrome of bronchial asthma with frequent attacks of asphyxiation, the second stage of respiratory distress), allergic rhinitis; lesions of joints (polyarthritis, polyarthralgia). The patient was treated with Methylprednisolonum at 16 mg, Endoxan® at 50 mg twice daily for 3 months and thereafter the doze was at 50 mg protractedly, Seretide® at 50/500 mcg/day. After one month the general condition of the patient improved; the blood count demonstrated white blood cells – 6,8×109/l, eosinophils – 9%, ESR – 16 mm/h. The reported dynamic clinical observation demonstrates a typical progression of CSS, allowing making the diagnosis despite of absence of morphological confirmation.
The clinical picture of CSS is characterized by the big polymorphism of manifestations depending on the stage of the disease. In 1984 J.Y. Lanham distinguished 3 phases in the progression of the disease . At the prodromale phase the clinical presentation, which can last up to 10 years, shows various allergic manifestations, including allergic rhinitis, polyposis and asthma. The most typical manifestation is bronchospasm, which eventually transforms into the severe form of asthma, refractory to bronchial spasmolytics and requires introduction of glucocorticosteroids (GCS). In most patients bronchial asthma is the major clinical syndrome for many years [4,5]. In 70% of patients the clinical presentation often begins with manifestations of allergic rhinitis, which is often complicated by recurring polyposis and subsequent sinusitis.
The characteristic feature of the second phase of the disease is peripheral and interstitial eosinophilia with lesions of different organs, most frequently the lungs, stomach and intestines: Loeffler’s syndrome, eosinophilic pneumonia, gastroenteritis.
The clinical picture of the final third phase is typically presented by the symptoms of systemic necrotizing vasculitis with lesions of the lungs, skin, heart, peripheral nerves, kidneys. In CSS generalization the severity of bronchial asthma reduces. Transient eosinophylic infiltrations of lungs have been found in 2/3 of the patients, which quickly regress in the introduction of GCS and can be developed at different stages of the disease. Pleural changes have been noted relatively often. And pleurisy with eosinophilia is revealed in 1/3 of patients.
Initially granulomatous eosinophilic gastroenteritis is manifested by the pain in the abdomen, diarrhea, gastrointestinal haemorrhage, and, thereafter, the subsequent vasculitis of the vascular wall with ischemia, which can be the cause of perforation, occur.
Before the third phase multiple lesions of the heart have been found in 35-60% of patients with CSS: myocarditis, cardiomyopathy, heart failure; coronaritis with the development of clinical signs of the acute coronary syndrome or myocardial infarction that can be the cause of patient’s death [6,7]. Exudative or restrictive pericarditis is rarely detected.
Skin lesions in CSS are characterized by the polymorphism: purpura erythema, urticaria, skin necrosis, livedo reticularis. Hemorrhagic rash (from petechia to apparent ecchymosis, etc) can occur.
Pathology of the nervous system is revealed in 80% of patients and in most cases peripheral mononeuritis multiplex and polyneuropathy is diagnosed, based on affection of vasa nervorum, mainly peroneal and ulnar nerves. Peripheral polyneuropathy may be accompanied by the severe pain syndrome. Signs of lesions of the central nervous system in the form of emotional disorders, less frequently hemorrhagic stroke and brain infarction, are revealed in every fourth patient.
Renal lesions are reported in more than half of patients, more often it is focal glomerulonephritis. Necrotizing fast-growing glomerulonephritis with the development of chronic renal failure can develop in patients with ANCA to myeloperoxidase.
Churg-Strauss syndrome can be suspected in adult patient with a history of bronchial asthma, rhinitis, eosinophilia with subsequent development of systemic manifestations as well as pulmonary infiltrates, cardiomyopathy, multiple polyarthritis. Among the laboratory signs eosinophilia is the major one, which is detected in 97% of patients, more frequent during the II phase of the disease. The content of peripheral blood eosinophils is grater than 10% of all leucocytes, and some patients show 30%-85%. The nonspecific changes include normochromal anemia, accelerated ESR and elevated level of CRP, the increase of inflammatory level of immunoglobulin, hypergammaglobulinemia.
ANCA examination is crucial in the differentiated diagnosis of vasculitides, including SLE. They are revealed in 40-60% of patients with CSS. In most ANCA-positive patients with CSS antibodies to myeloperoxidase with perinuclear stain (MPO-ANCA) are found. Renal lesions, peripheral neuropathy, central nervous system damage and purpura are frequently found in ANCA-positive form of the disease; in ANCA-negative patients the cardiac and respiratory tract involvement, fever is more frequent.
A morphological study is the compulsory component in the diagnosis of CSS. Skin, lungs and kidney biopsy material is used for diagnostics. A typical morphological sign of vasculitis is a prominent eosinophil-induced infiltration of wall of small vessels.
Currently, The American College of Rheumatology (ACR) distinguishes 6 criteria for this disease:
– a history of bronchial asthma or dyspnea, expiratory rhonchi;
– eosinophilia >10% on white blood cell count;
– mononeuropathy, mononeuritis multiplex or “socks-and-gloves” polyneuropathy;
– migratory or transient pulmonary infiltrates in X-ray examination;
– sinusitis, pain in the area of maxillary sinuses and X-ray alterations;
– extravascular eosinophilia at biopsy.
The presence of 4 or more of these signs is specific in 99,7% .
The treatment of the patient with CSS should correspond to the current treatment regimens and be comprehensive and individual. To induce the remission in case of ANCA-negative form and absence of signs of progression glucocorticosteroids (GCS) are prescribed. In ANCA-positive form of CSS and fast-growing glomerulonephritis introduction of GCS is supplemented with cytostatics. Timely treatment is important as delayed diagnosis can lead to a fatal outcome. Adequate therapy ensures 5-year survival rate for patients up to 75%. The main causes of death are heart failure and myocardial infarction.
In summary, CSS cannot be easily diagnosed as it requires the integration of clinical signs, past history, laboratory findings and additional methods of examination. At the same time it is necessary to emphasize that early diagnosis of the disease and drug therapy ensures prevention of irreversible changes and improves the prognosis for such patients.
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Yevdokiia М. Kitura
Higher State Educational Establishment of Ukraine
“ Ukrainian medical stomatological academy”,
Shevchenko st.23, 36011 Poltava, Ukraine