Leukocytoclastic vasculitis: a window to systemic churg strauss syndrome.

A twenty year old male presented with purpuric lesions with chronic painful ulcers over the lower extremities and a recurrent pruritic rash on the trunk for 10 years. He was diagnosed as idiopathic leukocytoclastic vasculitis (LCV) after investigations failed to reveal a systemic association. He was treated with immunosuppressants at each visit with partial remission. In 2004, he was diagnosed with bronchial asthma and allergic rhinitis. In his recent admission, he showed necrotic ulcers on legs and extensive shiny, truncal micropapules. Examination revealed maxillary sinus tenderness and loss of sensation on the medial aspect of the left lower limb. Biopsy of ulcer and the micropapules showed the presence of extravascular eosinophils, while hematological investigations showed peripheral eosinophilia of 18%, raised serum Immunoglobulin E (IgE), Anti nuclear antibody (ANA) positivity and negative antineutrophil cytoplasmic antibody (ANCA). Radiography confirmed maxillary sinusitis, nerve conduction studies revealed mononeuritis of the anterior tibial nerve and pulmonary function tests (PFT) were normal. Clinical examination and investigations pointed towards the diagnosis of Churg-Strauss syndrome (CSS). This report highlights the development of full-blown CSS over a period of 12 years in a patient initially diagnosed as idiopathic LCV, emphasizing the need for regular follow-up of resistant and recurrent cases of LCV.

Introduction

Churg–Strauss allergic granulomatosis is a rare form of systemic vasculitis with associated allergic diathesis. It is characterized by an eosinophil-rich granulomatous inflammation involving the respiratory tract and necrotizing vasculitis involving the medium-sized vessels, associated with asthma and eosinophilia. This report intends to highlight the development of full-blown Churg Strauss syndrome (CSS) over a period of 12 years in a patient initially diagnosed and treated as idiopathic leukocytoclastic vasculitis (LCV), emphasizing the need for regular follow-up of such cases.

Case Report

A twenty year old male presented to us in October 1998 with painful, recurrent, small ulcers on lower legs. The lesions began as multiple, purpuric macules, progressing to small ulcers with severe pain and restricted mobility. Examination showed multiple small punched-out ulcers covered with eschar and perilesional erythema on the extensor aspect of lower legs including dorsa of feet [Figure 1]. Biopsy confirmed the diagnosis as leukocytoclastic vasculitis. Serologic investigations for associated autoimmune etiology including anti nuclear antibody (ANA)/ Anti double stranded DNA (anti-ds-DNA) and antineutrophil cytoplasmic antibody (ANCA). were negative and the patient was treated with systemic and topical corticosteroids. Lesions remitted partially over the following three months, with subsequent flares associated with the development of upper respiratory tract symptoms. The presenting features at each flare were the same and the patient received multiple anti-inflammatory and immunosuppressive medications, singly and in combination viz. oral corticosteroids, dapsone, colchicine, chloroquine, thalidomide, azathioprine and dexamethasone cyclophosphamide IV pulse over a period of four years. Treatment led to partial remission each time.

Figure 1

Stellate-shaped ulcerations with overlying hemorrhagic crusts healing with atrophic scars seen on the dorsa of feet and legs bilaterally

In March 2004, he additionally developed generalized pruritic micropapular rash [Figure 2], rhinitis and episodic breathlessness that worsened in cold weather. The pulmonologist diagnosed the condition as allergic rhinitis with bronchial asthma and prescribed bronchodilators. Histopathology of the rash was unremarkable and other investigations for autoimmune etiology were negative.

Figure 2

Micropapular rash involving the back

In April 2008, patient had recurrence of the painful ulcers along with cough, cold, dyspnea; and loss of sensation on the medial aspect of the left leg and foot of 15 days duration. Clinical examination revealed bilateral maxillary sinus tenderness and wheezes in both lungs. There was hypoesthesia to touch, pain and temperature along the medial border of the left foot. Investigations showed a peripheral eosinophilia of 18%, Absolute eosinophil count of 1235/cmm, and raised serum IgE of 375 IU (n=200 IU/ml). Erythrocyte sedimentation rate (ESR) was normal, while ANA/anti-DsDNA/cANCA were negative. Bronchial provocation test was positive. Radiograph of the paranasal sinuses showed haziness in the bilateral maxillary sinuses. X-ray of chest was normal, but high-resolution computed tomography (HRCT) of the chest showed focal fibronodular lesions in the inferior lingula. Biopsy from an ulcerated lesion on the leg and from a truncal papule showed similar histology with superficial and deep perivascular mixed infiltrate consisting of multiple lymphocytes, histiocytes and plasma cells, with the presence of extra vascular eosinophils. The vessel walls were thickened with infiltration inside the vessel wall and there was extravasation of RBCs [Figures 3–5]. A neurology referral confirmed the affected hypoesthesia of left foot as a mononeuropathy. Thus, based on the constellation of findings of bronchial asthma, maxillary sinusitis, focal pulmonary nodule, mononeuropathy; and peripheral eosinophilia with the presence of extravascular eosinophils in biopsy, the patient was diagnosed as a case of CSS.

Figure 3

4× magnification-ulcerated epidermis with scale crust and perivascular mixed cell infiltrate involving the upper and mid dermis (H and E stain)

Figure 5

40× magnification showing thickened vessel wall with infiltrate inside the walls with fibrin deposition (H and E stain)

40× magnification showing thickening of the vessel wall with infiltration of lymphocytes, histiocytes and plasma cells in and around the vessel walls with the presence of extravascular eosinophils and extravasated RBCs (H and E stain)

The patient was started on oral corticosteroids in tapering doses, along with mycophenolate mofetil and bronchodilators. He is currently in remission with regards to the systemic disease as well as the skin [Figure 6].

Figure 6

Healing of the ulcerations on the dorsum of foot post treatment

Discussion

The International Consensus Conference held in Chapel Hill defined CSS as an eosinophil-rich granulomatous inflammation involving the respiratory tract, and necrotizing vasculitis involving the medium-sized vessels, associated with asthma and eosinophilia. Each component of these definitions (histopathology, eosinophilia in blood and tissues and asthma) helps define the disease, but none of these features individually is specific for CSS, and not every patient has all the features. It is a rare disease with incidence of 2.5 per 100,000 patients and a slight male preponderance.

CSS has been divided into three phases that may or may not be sequential: A prodromal period with allergic rhinitis, nasal polyposis and asthma; the second phase of peripheral and tissue eosinophilia, Loffler's syndrome, chronic eosinophilic pneumonia or eosinophilic gastroenteritis; and the third vasculitic phase that may involve any organ.

Our patient did not have the sequential appearance of the three classical phases of the disease. The vasculitic lesions were the initial presentation. The allergic rhinitis, asthma and peripheral eosinophilia developed much later. In fact, no systemic involvement could be detected in the patient for six years after his presentation with cutaneous leukocytoclastic vasculitis.

The most frequent site of involvement in CSS is heart which was not involved in our case. Skin involvement is seen in more than two thirds of patients and ranges from erythematous maculopapules resembling erythema multiforme, hemorrhagic lesions, and cutaneous and subcutaneous nodules. Interestingly, the presentation of this patient with a micropapular eruption with histopathological picture showing extravascular eosinophils has yet not been reported in the literature.

The American College of Rheumatology (ACR) criteria for diagnosis are enumerated in Table 1.[1] Our patient fulfilled five out of six criteria. Systemic vasculitis involving the renal system with azotemia and proteinuria, gastrointestinal involvement, and cardiomyopathy are poor prognostic indicators.

Table 1

ACR criteria for classification of churg–strauss syndrome

Corticosteroids are the first-line therapy in all cases.[23] If vasculitic symptoms are uncontrolled or if large doses of steroids are required for control, cyclophosphamide may be added.[45] In patients with seemingly better prognosis and less severe disease, methotrexate (MTX) is used. In severe cases, infliximab and etanercept may be added for a limited period. Mycophenolate mofetil is considered to be a reasonable option in the treatment of non-life-threatening recurrent or resistant vasculitis and may obviate the immediate need for recurrent use of cytotoxic agents.

In our patient, combination therapy of corticosteroid and mycophenolate mofetil resulted in remarkable remission for a significant period, as compared to the previous regimens.

This case is being reported for its rarity and the development of full-blown CSS over a period of ten years in a patient initially diagnosed and treated as idiopathic LCV, emphasizing the need for regular follow-up of cases of therapeutically resistant and recurrent cases of leukocytoclastic vasculitis.