BRIEF RESEARCH COMMUNICATION


https://doi.org/10.5005/jp-journals-11007-0086
The Indian Journal of Chest Diseases and Allied Sciences
Volume 65 | Issue 3 | Year 2023

Churg–Strauss Syndrome


Romman Fatima1, Dharampal Bansal2, Syed Taha Mahmood3, Afra Fatima4, Viquasuddin Mohammed5

1,5Department of Internal Medicine, Olive Hospital, Hyderabad, Telangana, India

2Department of Internal Medicine/Critical Care, Olive Hospital, Hyderabad, Telangana, India

3Department of Pulmonology, Olive Hospital, Hyderabad, Telangana, India

4Department of Internal Medicine, Shadan Institute of Medical Sciences, Hyderabad, Telangana, India

Corresponding Author: Viquasuddin Mohammed, Department of Internal Medicine, Olive Hospital, Hyderabad, Telangana, India, Phone: +91 9885625121, e-mail: drmdviquasuddin@gmail.com

How to cite this article: Fatima R, Bansal D, Mahmood ST, et al. Churg–Strauss Syndrome. Indian J Chest Dis Allied Sci 2023;65(3):167–170.

Source of support: Nil

Conflict of interest: None

Received on: 09 August 2023; Accepted on: 01 November 2023; Published on: 05 February 2024

ABSTRACT

Churg–Strauss syndrome an antineutrophilic cytoplasmic antibody (ANCA)-mediated vasculitis has an estimated prevalence of around 10.7 cases per million adults with the median age of presentation being 40 years. It is an uncommon vasculitis to be seen in pediatric age groups which when found has a poorer prognosis due to cardiac involvement and associated manifestations. Its pathophysiology is based on the immune-mediated activation of eosinophils followed by the release of chemokines, such as eotaxin-3, CCL17, major basic protein and many other intermediates that cause tissue damage. The case described, presented with recurrent sinusitis, allergic manifestations with sudden onset purpuric ankle rash and marked hypoxia-induced respiratory distress. Workup revealed marked eosinophilia and very high IgE levels pointing towards ANCA-mediated vasculitis. The patient was managed with pulse dose steroid therapy for remission and maintenance treatment with long-term steroids. The patient was discharged in stable condition with a monthly follow-up with the primary.

Keywords: Antineutrophilic cytoplasmic antibody, Corticosteroid, Hypoxia, Pulse steroid, Respiratory distress.

ABBREVIATIONS USED IN THIS ARTICLE

ANA = Antinuclear antibody; ANCA = Antineutrophilic cytoplasmic antibody; IVIG = Intravenous immunoglobulin G; VDI = Vasculitis damage index.

BACKGROUND

A case of acute asthma exacerbation with unusually elevated serum eosinophils and immunoglobulin E levels was later found to have Churg–Strauss syndrome. Churg–Strauss syndrome also called eosinophilic granulomatosis with polyangiitis is a type of necrotizing small vessel vasculitis. The American College of Rheumatology has defined Churg–Strauss syndrome as the presence of asthma, migratory infiltrates in the lung, paranasal sinus abnormalities, polyneuritis or mononeuritis multiplex, and eosinophilic infiltrate in the tissue biopsy with peripheral blood eosinophilia1 (Churg–Strauss Syndrome – StatPearls, 2023).

It is an immune-mediated vasculitis with anti-neutrophilic cytoplasmic antibodies like p-antineutrophilic cytoplasmic antibody (p-ANCA) or MPO-ANCA positivity2 (Yu, n.d.).

It can present with two phenotypic manifestations, type I vasculitis phenotype, and type II eosinophilic asthma phenotype. Syndromic features of vasculitic phenotypes have myalgias, neuropathy, migrating polyarthralgia, and renal involvement in the form of necrotizing crescentic glomerulonephritis, hematuria, and leukocytoclastic vasculitis; while syndromic features of the eosinophilic asthma phenotype3 (Vaglio, n.d.) include a significantly high risk of developing myocarditis and coronary manifestations along with strong positivity for anti-neutrophilic cytoplasmic antibodies. Asthma is the cardinal feature and precedes systemic features in almost all cases; typically, late onset and becomes more severe until the onset of vasculitis.

CASE PRESENTATION

A 36-year-old male presented to the outpatient department with shortness of breath and bouts of productive cough for 6 days with whitish sputum, which was not associated with fever, chest pain, or hemoptysis but with a long-standing history of allergic manifestations for which extensive workup was done prior to the presentation. He had a history of COVID-19 infection in the recent past but did not require hospitalization and was managed at home conservatively. The onset of the above manifestations was associated with a pruritic bright purple-colored purpuric rash on bilateral ankles which was associated with intense itching pain and swelling as shown in Figure 1.

Fig. 1: Purpuric ankle rash

On physical examination, the patient was found to have tachypnea, diffuse bibasilar rhonchi with a characteristic petechial rash on bilateral lower limbs, that was coalescing in nature without any focal neurological deficits. The abdomen was soft, non-tender, and showed no features of organomegaly (ruling out eosinophilic leukemias). In view of the sudden onset of rash and long-standing allergic history, the patient was subjected to further workup and was admitted to the hospital as he was unable to maintain saturation at room air and was profoundly hypoxic (SpO2–88% on room air).

The patient was started on supplemental oxygen support, nebulization with beta-adrenergic agonists and steroids administered, and his vaccination status was reviewed. During the course in the hospital, the patient complained of severe bouts of cough with expectoration, for which antibiotics were initiated and inflammatory markers along with a complete blood count were sent to look for any infection. Chest X-ray revealed bibasilar congestion with a marked increase in broncho vascular markings.

The rash was evaluated for its progression and in view of suspicion of its vasculitic nature. The investigations revealed a markedly elevated absolute peripheral eosinophilic count (of 17810 cells/cumm), 12% differential eosinophil count, and a serum immunoglobulin E level of 3000 IU/mL.

The patient had a slight improvement in his baseline cough and continued to require oxygen support, in view of which a high-resolution CT chest was performed. The CT findings of diffuse segmental and subsegmental bronchial wall thickening in bilateral lung parenchyma with multiple peribronchovascular tiny nodular opacities (tree in bud appearance) and minimal pleural effusion suggest infectious etiology as shown in Figures 2 to 4, respectively. RT-PCR for COVID-19 was performed, which turned out negative. The patient was screened for vasculitis and investigational p-ANCA, and C-ANCA along with antinuclear antibody (ANA) profile was sent. The p-ANCA levels were significantly high and subsequently, a bronchoscopy was done to assess the bronchial lavage for eosinophilia followed by a skin biopsy to confirm tissue eosinophilia.

Fig. 2: High-resolution CT scan showed peribronchovascular nodular opacities – tree in bud appearance

Fig. 3: Sub-segmental bronchial thickening-lung window

Fig. 4: Multifocal opacities in CT lung window

The bronchoalveolar lavage fluid analysis revealed lymphocytosis, few squamous cells in the proteinaceous background with no growth of organisms on culture, while the skin biopsy showed focal areas of the necrotic epidermis with orthokeratosis, intraepidermal bulla containing fibrinous material, neutrophils, red blood cells as shown in Figure 5, and karyorrhectic debris within. The upper dermis revealed fibrinoid necrosis and numerous extravasated red cells that confirmed the presence of leukocytoclastic vasculitis and the diagnosis of Churg–Strauss syndrome.

Fig. 5: Skin biopsy showing fibrinoid necrosis, intraepidermal red blood cells and neutrophils – leukocytoclastic vasculitis

The patient was treated with an intravenous methylprednisolone pulse dose (15 mg/kg) and a combination of inhaled levosalbutamol and ipratropium that resulted in marked symptomatic improvement and was hence discharged with a course of long-term oral steroid therapy.

DISCUSSION

Churg–Strauss syndrome has an overall incidence of 4 per million population. It has a 5-year survival rate of around 90% and shows a good response to steroid therapy. However, the prognosis of the disease is calculated using the five-factor score that predicts high mortality and a rapid course of progression. The five factors include proteinuria (greater than 1 gram per day), renal insufficiency (Creatinine greater than 1.58 mg/dL), cardiomyopathy, gastrointestinal tract involvement, and central nervous system involvement. Cardiac manifestations have the worst prognosis and the vasculitis damage index (VDI) can be used to assess the overall organ damage and the gold standard sural nerve biopsy can be performed in those who have neurological manifestations. Studies have shown that markers like serum IgG4 levels and CCL174 (Gross, n.d.) correlate with the disease activity and can be utilized to assess the state of remission.

The pulse dose therapy for steroid responders includes oral prednisone: 1 mg/kg daily for 3 weeks, followed by 5 mg every 10 days tapering to 0.5 mg/kg. Then taper 2.5 mg every 10 days to the minimal dose. While most patients show good responses to therapy, patients with relapse or poor responses can be managed with alternative regimens. Oral azathioprine 2/mg/kg daily for at least 6 months or cyclophosphamide pulses (600 mg/m2) every 2 weeks for 1 month, then every 4 weeks afterwards are other effective treatment options.

The refractory disease states are managed with plasmapheresis, Intravenous immunoglobulin G (IVIG), interferon alpha, TNF inhibitors, and rituximab5 (Rituximab as Induction Therapy in Eosinophilic Granulomatosis With Polyangiitis Refractory to Conventional Immunosuppressive Treatment: A 36-Month Follow-up Analysis, 2017), where plasmapheresis is highly useful for those patients who present with rapidly progressive glomerulonephritis or alveolar hemorrhage. It remains the most under-diagnosed vasculitides due to its highly varied presentation.

REFERENCES

1. Chakraborty RK, Aeddula NR. Churg-Strauss Syndrome. [Updated 2023 Mar 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.

2. Hsieh SC, Yu HS, Cheng SH, et al. Anti-myeloperoxidase antibodies enhance phagocytosis, IL-8 production, and glucose uptake of polymorphonuclear neutrophils rather than anti-proteinase 3 antibodies leading to activation-induced cell death of the neutrophils. Clin Rheumatol 2007;26(2):216–224. DOI: 10.1007/s10067-006-0285-3.

3. Zwerina J, Bach C, Martorana D, et al. Eotaxin-3 in Churg-Strauss syndrome: A clinical and immunogenetic study. Rheumatology (Oxford) 2011;50(10):1823–1827. DOI: 10.1093/rheumatology/keq445.

4. Schönermarck U, Csernok E, Trabandt A, et al. Circulating cytokines and soluble CD23, CD26 and CD30 in ANCA-associated vasculitides. Clin Exp Rheumatol 2000;18(4):457–463. PMID: 10949720.

5. Thiel J, Troilo A, Salzer U, et al. Rituximab as induction therapy in eosinophilic granulomatosis with polyangiitis refractory to conventional immunosuppressive treatment: A 36-month follow-up analysis. J Allergy Clin Immunol Pract 2017;5(6):1556–1563. DOI: 10.1016/j.jaip.2017.07.027.

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