Your Federal Quarterly Tax Payments are due April 15th Get Help Now >>



									British Journal of Rheumatology 1997;36:273–275

                                                            CASE REPORT
                                        and G. CAMBRIDGE
        Bloomsbury Rheumatology Unit/Division of Rheumatology, Department of Medicine, *Department of Physiology
                               and †Eye Department, University College London, London

Occular involvement is infrequent and blindness rare in Churg–Strauss syndrome. We describe a patient with Churg–Strauss
syndrome who presented with blindness. This was associated with the appearance of circulating autoantibodies to
K : Churg–Strauss syndrome, Anti-myeloperoxidase antibodies, Blindness.

C–S syndrome is a triad of asthma,                                infraspinatus muscles with brisk reflexes in that arm. These
eosinophilia (q1 × 109/l) and a systemic vasculitis                         findings had been long standing and were thought to be due
involving two or more extrapulmonary organs.                                to his cervical nerve root compression. His investigations
Whereas a number of different organs may be affected,                         showed normal renal function as well as normal full blood
involvement of the eye is uncommon. We describe a                           count and ESR, except for an eosinophilia of 12%. No
patient with Churg–Strauss syndrome who developed                           autoantibodies, including anticardiolipin antibodies, were
blindness.                                                                  detected on routine screening. Dilute Russell’s viper venom
                                                                            time was equivocal. His echocardiogram was normal. Carotid
                      CASE REPORT                                           Doppler studies showed bilateral 60–80% stenosis of the
                                                                            internal carotid arteries. Subsequently, a digital subtraction
   A 58-yr-old Caucasian male was admitted in December                      angiogram showed there was no operable lesion. He was
1993 with a history of transient blindness in the left eye. He              treated with i.v. heparin for 3 days and his aspirin dose was
had experienced frequent episodes of visual loss over the                   increased to 300 mg daily, and he was discharged.
previous 10 weeks. These episodes occurred every 2–3 days                      He was readmitted 4 weeks later with blindness in the left
and lasted 3–4 min, but always with complete recovery of                    eye which had developed over a 24 h period. He also gave a
vision. There were no other associated neurological                         history of arthralgia of the shoulders, elbows and wrists. On
symptoms. In the previous medical history, it was noted that                examination, vasculitic lesions were noted overlying the
he had had childhood asthma with allergic rhinitis which                    knees, elbows, wrists, the fifth digit in the left hand and both
resolved, only to recur at age 52 yr. On this occasion it                   fifth toes. He also had a mildly swollen right ankle.
became severe, requiring oral steroid treatment as well as                  Ophthalmic examination showed that his visual acuities were
inhaled steroids and bronchodilators. He developed severe                   right 6/6, left 6/12 corrected. (His visual acuity had been 6/6
side-effects, including osteoporotic fractures of several ribs,              corrected on both sides following his cataract operations.)
compression of thoracic vertebrae, and cataracts which were                 There was oedema of the left macular retina and two cotton
treated with lens implants. He had also had papilloma of the                wool spots. There was no obvious retinal vascular disease
bladder, haemorrhoids and cervical spondylosis with cervical                and no emboli were seen in the retinal circulation (Fig. 1).
nerve root compression. In the family history, his father had               Clinically, the picture was consistent with macular
had a cerebrovascular accident aged 70 and his mother had                   retinal artery occlusion. The rest of his examination was
had urticaria.                                                              unremarkable. His blood pressure was 125/70 mmHg.
   The patient had never smoked and his medications on                         On this admission, investigations showed a normal Hb and
admission were prednisolone 6 mg o.d., aspirin 150 mg o.d.                  platelet count, but a raised white cell count (17.4 × 109/l) with
and Ventolin inhalers. Owing to the side-effects of oral                     eosinophilia (53%). His ESR (Westergen) was raised
steroids, he was started on inhaled fluticasone propionate                   (35 mm/h), but renal and liver function, serum triglycerides
which enabled the reduction of his daily oral steroid dose                  and cholesterol, serum protein electrophoresis, immuno-
from 30 to 6 mg. During this period, nodules on his elbows                  globulins and CRP were normal. The autoantibody screen
were noted which were thought to be cholesterol deposits.                   was negative, except for a positive ANCA with a p-ANCA
   On examination, his blood pressure was 134/86 mmHg and                   staining pattern. Antigen-specific ELISAs showed that the
the general examination was normal. There were no                           p-ANCA were specific for myeloperoxidase (MPO) and were
ophthalmic signs, including retinal changes on dilated fundus               of the IgG class (53% of positive control serum; upper limit
examination. Neurological examination revealed mild wast-                   of normal range 20%). In addition, using subclass-specific
ing of the medial aspect of the right forearm, right supra- and             mouse monoclonal antibodies, it was found that the
                                                                            anti-MPO antibodies were predominantly of the IgG4
  Submitted 8 February 1996; revised version accepted 19 July 1996.         subclass (data not shown). Retrospective serum samples were
  Correspondence to: N. Sutcliffe, Rheumatology Unit, 4th Floor,             also available and tested for anti-MPO antibodies (Fig. 2). As
Arthur Stanley House, 40–50 Tottenham Street, London W1P 9PG.               is shown, although anti-MPO antibodies were slightly above

                                                                                                 = 1997 British Society for Rheumatology
274                              BRITISH JOURNAL OF RHEUMATOLOGY VOL. 36 NO. 2

the normal range (q20% of the positive control), significant
levels of anti-MPO antibodies were found only at diagnosis
at the same time as the maximal eosinophil count. Midstream
urine showed a trace of protein, 24 h urinary protein was
normal. A skin biopsy of the left little finger showed changes
of a wedge-shaped dermal infarct with overlying, probably
secondary, bulla formation. A moderate number of
eosinophils were present in the associated inflammatory cell
infiltrate. Thromboses were present within several small
vessels of the superficial dermis. The appearances were of a
dermal/epidermal infarct. Histological appearances were
consistent with an obstructed vessel in the deeper dermis and
   In view of late-onset asthma, eosinophilia, skin vasculitis
with extravascular eosinophils on the skin biopsy and
presumed retinal vasculitis, a diagnosis of Churg–Strauss
syndrome was made. In addition, elevated levels of
                                                                        F. 2.—Serial measurements of eosinophil count and circulating
circulating anti-MPO antibodies were found. Subsequently,
                                                                        anti-myeloperoxidase antibodies of patient BG over the time of
the patient was treated with i.v. and oral steroids followed by
                                                                        study. The upper limit of the normal range for anti-MPO antibodies
azathioprine. His skin lesions resolved and he has had no
                                                                        is indicated by the vertical line.
further symptoms of asthma. However, 2 yr later, there has
been little improvement in vision in the left eye. He has
managed to reduce his prednisolone to 5 mg o.d. and
continued to take azathioprine 150 mg o.d.                              Another patient who had visual loss also had a
                                                                        temporal artery biopsy which showed vasculitis with
                    DISCUSSION                                          eosinophils, but no giant cells. This patient had an
   Ocular involvement in Churg–Strauss syndrome is                      improvement of visual acuity with high-dose steroid
infrequent, but includes scleritis, uveitis, corneal                    treatment [1]. Another patient with severe visual loss
ulcerations, conjunctival inflammation, cranial nerve                    due to an acute bilateral sequential optic neuropathy
palsies, retinal infarctions, amaurosis fugax and                       had treatment with i.v. cyclophosphamide and had no
ischaemic optic neuropathy [1]. Blindness is a rare                     visual recovery [2]. Churg–Strauss syndrome is in the
finding and has been described previously in only five                    differential diagnosis of amaurosis fugax and, if
patients [1–5]. Three of these patients had monocular                   considered, an early diagnosis may prevent blindness.
blindness which was irreversible despite treatment with                    Circulating ANCA with specificity for MPO have
steroids [3–5]. Two underwent temporal artery                           been described in some reports as being present in from
biopsies; one was normal [3], the other showed                          56 to 75% of patients with Churg–Strauss syndrome
histology consistent with Churg–Strauss syndrome [4].                   [6, 7]. Anti-MPO antibodies of the IgG4 subclass have
                                                                        been associated with other forms of ANCA-associated
                                                                        vasculitis [8], but no extensive studies of the subclass
                                                                        distribution of anti-MPO antibodies in Churg–Strauss
                                                                        syndrome in particular have been reported. The IgG4
                                                                        subclass is associated with prolonged antigen exposure,
                                                                        eosinophilia and hypersensitivity. It is the predominant
                                                                        and pathogenic immunoglobulin subclass of autoanti-
                                                                        bodies in patients with epidemic pemphigus bullosum
                                                                        [9] and is also over-represented in anti-colon antibodies
                                                                        in ulcerative colitis [10]. It has been proposed that in
                                                                        vasculitis, IgG1 and IgG3 subclass anti-MPO anti-
                                                                        bodies may be pathogenic due to their ability to
                                                                        cross-link FcgRIIa receptors and surface-bound MPO
                                                                        on neutrophils, resulting in neutrophil activation and
                                                                        endothelial cell damage [11]. The signalling mechanism
                                                                        for neutrophil activation would therefore be through
                                                                        the intracellular domain of the FcgRIIa receptor.
                                                                        Neutrophils do not, however, possess Fc receptors for
                                                                        IgG4, neither does this immunoglobulin subclass
                                                                        significantly fix complement. In this case report, the
                                                                        patient developed predominantly IgG4 subclass anti-
                                                                        MPO antibodies within a relatively short period of
F. 1.—Photograph of left fundus from a 40° colour photograph.         time, and their appearance also correlated with an
Two cotton wool spots are located temporal to the optic disc. Retinal   acute vasculitic episode. Patients with ANCA-related
vascular calibres were considered within normal limits with no          vasculitis have also been described in whom the only
evidence of retinal emboli.                                             subclass of immunoglobulin present is IgM [12]. Fc
                                SUTCLIFFE ET AL.: CHURG–STRAUSS VASCULITIS                                               275

receptors for IgG4 are, however, present on basophils           6. Guillevin L, Visser H, Noel LH, Pourrat J, Vernier I,
and mast cells. In vasculitis, the preferential production         Gayraud M et al. Antineutrophil cytoplasmic antibodies
of IgG4 subclass anti-MPO antibodies may allow                     in systemic polyarteritis nodosa with and without
binding of antibody/antigen complexes to basophils or              Hepatitis B virus infection and Churg–Strauss syndrome.
                                                                   J Rheumatol 1993;20:1345–9.
mast cells, rather than clearance of complexes through          7. Cohen-Tervaert JW, Limburg PC, Elema JD, Huitema
conventional Fc receptor and complement-mediated                   MG, Horst G, The TH et al. Detection of autoantibodies
pathways. Basophils and mast cells are also known to               against myeloid lysosomal enzymes: a useful adjunct to
release mediators such as histamine, transforming                  classification of patients with biopsy proven necrotising
growth factor-b and interleukin 4 which can affect                  arteritis. Am J Med 1991;91:59–66.
B-cell and neutrophil function following cross-linking          8. Brouwer E, Cohen Tervaert JW, Horst G et al.
of IgG4 Fc receptors [13]. This case study suggests that           Predominance of IgG1 and IgG4 sub-class of antineu-
the functional properties of IgG4 anti-MPO antibodies              trophil cytoplasmic antibodies (ANCA) in patients with
should also be investigated.                                       Wegener’s granulomatosis and clinically related dis-
                                                                   orders. Clin Exp Immunol 1991;83:379–86.
                                                                9. Emery DJ, Diaz LA, Fairley JA, Lopez A, Taylor
                          R                               AF, Giudice GJ. Pemphigus foliaceus and pemphigus
 1. Alan RA, Richard L, Kenneth RA, Elliot KC, Myron S,            vulgaris autoantibodies react with the extracellular
    Richard AF. Reversible monocular blindness complicat-          domain of desmoglein 1. J Invest Dermatol 1995;104:
    ing Churg–Strauss syndrome. J Rheumatol 1994;21:363–           323–8.
    5.                                                         10. Ohara M, Hibi T, Watanabe N, Kobayashi K, Takaishi
 2. Acheson JF, Cockerell OC, Bentley CR, Sanders MD.              H, Hayashi A et al. Immunoglobulin G (IgG) sub-class
    Churg–Strauss vasculitis presenting with severe visual         distribution of anticolon antibodies in ulcerative colitis.
    loss due to bilateral sequential optic neuropathy. Br J        J Gastroenterol Hepatol 1995;10:158–64.
    Ophthalmol 1993;77:118–9.                                  11. Mulder AHL, Heeringa P, Brouwer E, Limburg PC,
 3. Weinstein JM, Chui H, Lane S, Corbett J, Towfighi J.            Kallenberg CGM. Activation of granulocytes by
    Churg–Strauss syndrome (allergic granulomatous angi-           anti-neutrophil cytoplasmic antibodies (ANCA): a
    itis): Neuro-ophthalmologic manifestations. Arch Oph-          FcgRII-dependent process. Clin Exp Immunol
    thalmol 1983;101:1217–20.                                      1994;98:270–8.
 4. Conn DL, Dickson ER, Carpenter HA. The association         12. Cambridge G, Williams M, Leaker B, Corbett M, Smith
    of Churg–Strauss vasculitis with temporal artery               CR. Anti-myeloperoxidase antibodies in patients with
    involvement, primary biliary cirrhosis, and polychondri-       rheumatoid arthritis: prevalence, clinical correlates, and
    tis in a single patient. J Rheumatol 1982;9:744–8.             IgG subclass. Ann Rheum Dis 1994;53:24–9.
 5. Finan MC, Winkelmann RK. The cutaneous extravascu-         13. Fagan DL, Slaughter CA, Capra JD, Sullivan TJ.
    lar necrotising granuloma (Churg–Strauss granuloma)            Monoclonal antibodies to immunoglobulin G4 induce
    and systemic disease. A review of 27 cases. Medicine           histamine release from human basophils in vitro. J
    1983;62:142–58.                                                Allergy Clin Immunol 1982;70:399–404.

To top