Churg–Strauss syndrome: the use of cyclophosphamide in mononeuritis

A. Y. Hoi and E. F. Morand

Monash Medical Centre, Rheumatology, Clayton, Victoria, Australia

SIR, The treatment of Churg–Strauss syndrome (CSS) has traditionally consisted of corticosteroid monotherapy [1, 2]. The use of adjuvant immunosuppressive therapy is controversial [3] and is generally reserved for severe disease [4, 5], even though the concept of severe disease is not clearly defined. We wish to report two cases of CSS presenting with mononeuritis multiplex. Both patients responded inadequately to corticosteroid, but the introduction of cyclophosphamide coincided with halting of disease progression.

The first case was a 67-yr-old man with a history of steroid-dependent asthma and chronic sinusitis, who presented with a 6-week history of malaise, progressive limb weakness and paraesthesia. He had been on 15 mg/day of prednisolone for almost 20 yr. He described an undiagnosed episode of dysarthria and right temporal headache 15 yr ago, with residual bulbar dysfunction. Four years ago, he was treated for an episode of subacute non-infectious colitis with corticosteroids.

On presentation, he reported multifocal neurological symptoms affecting all limbs. Neurological signs progressed despite prednisolone 20 mg daily, and he developed a wrist drop and transient diplopia in addition to the patchy sensorimotor neuropathy. Notably, there was no significant worsening of his asthma and no new medication, including leukotriene antagonists. Apart from the neurological signs, the rest of the examination was unremarkable. Investigation results are summarized in Table 1Go.


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TABLE 1. Summary of investigations

 
CSS was diagnosed in accordance with the 1990 American College of Rheumatology classification criteria [6]. Neither tissue eosinophilia nor extravascular granulomata were found on sural nerve, muscle or temporal artery biopsies. Nasal polyp and maxillary sinus biopsies demonstrated a mixed inflammatory infiltrate with foci of intense active inflammation around a small blood vessel.

This patient was treated with intravenous (i.v.) methylprednisolone 1 g for 3 days and subsequent prednisolone 75 mg daily and i.v. cyclophosphamide 15 mg/kg monthly for 6 months. Eosinophilia and inflammatory markers responded within days and there was no further neurological progression or other organ involvement after beginning cyclophosphamide. He was weaned completely from prednisolone and weekly oral methotrexate was substituted for cyclophosphamide after 6 months.

The second case was a 56-yr-old man with a background of asthma and chronic sinusitis managed on inhaled corticosteroid and infrequent salbutamol, presenting with a 4-week history of constitutional symptoms, severe myalgia and arthralgia, dyspnoea and paraesthesia. His symptoms failed to improve despite oral corticosteroids and doxycycline. On examination there was an area of numbness over the dorsum of his right foot, consistent with an L5 dermatome. Examination was otherwise unremarkable. His investigation results are also summarized in Table 1Go.

In view of his neurological symptoms, he was treated with i.v. methylprednisolone 1 g for 3 days then prednisolone 50 mg daily. Symptoms, eosinophil count and the C-reactive protein (CRP) concentration improved. Over the following 2 weeks, he developed further paraesthesia in the fingers and severe shooting pain in the right leg. On examination, there was weakness of ankle dorsiflexion on the right, absent ankle jerks, and sensory loss over the dorsum of his hands and feet. He also developed bilateral ankle synovitis.

The initial peripheral eosinophilia had resolved, but the CRP remained high at 100 mg/l. We gave him three further doses of i.v. methylprednisolone and commenced i.v. cyclophosphamide 15 mg/kg monthly. He had progressive symptomatic improvement and no new clinical manifestations related to CSS.

Most studies that examine treatment outcomes of primary vasculitides have not separated CSS as a distinct entity. Historically, CSS has often been grouped with other vasculitides, such as polyarteritis nodosa and microscopic polyangiitis [5, 7, 8]. Despite their similarities, there are important differences in their natural history and prognosis.

Although CSS is often considered to have a relatively good prognosis, with a high remission rate on treatment and low mortality [9], poor clinical outcomes have occurred. Most deaths have been directly attributable to ongoing active vasculitis in vital organs. Long-term sequelae from CSS are often the result of neurological or cardiac involvement. The five-factors score (FFS) is a prognostic index based on disease severity at onset, to predict survival [8]. The five clinical features identified as being associated with poor outcome are proteinuria, severe gastrointestinal tract involvement, renal impairment, cardiomyopathy and central nervous system involvement; notably, the list does not include mononeuritis multiplex.

Mononeuritis multiplex is the second most common extrapulmonary manifestation of CSS [7, 9], and can result in long-term disability. Motor and sensory deficits can be debilitating. Cranial nerves can also be involved. Although Guillevin et al. [8] did not demonstrate a statistically significant correlation between mononeuritis multiplex and poor survival, it can certainly contribute significantly to short- and long-term morbidity in these patients.

In contrast to the perception that CSS is adequately treated with corticosteroids alone, both of our cases demonstrated neurological progression despite corticosteroid therapy. The presence of mononeuritis multiplex should be regarded as a serious complication of CSS and warrants more aggressive therapy. Although the FFS is a useful index, the factors identified are not all-inclusive. Corticosteroids have dramatically improved the prognosis in CSS, but the adjuvant use of immunosuppressive agents, particularly cyclophosphamide, can lead to disease remission in severe cases. We favour the use of i.v. rather than oral cyclophosphamide, on the basis of the study by Gayraud et al. [10]. Although the duration of treatment required is unclear, we recommend at least 6 months of cyclophosphamide.

Notes

Correspondence to: A. Y. Hoi. E-mail: ahoi{at}lambert.net.au Back

References

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Accepted 5 July 2002