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Recurrent uveitis in a patient with adult onset cyclic neutropenia associated with increased large granular lymphocytes
  1. ALEJANDRO RODRIGUEZ
  1. Immunology and Uveitis Service, Department of Ophthalmology. Massachusetts Eye and Ear Infirmary, Harvard Medical School. Boston, MA, USA
  2. Division of Rheumatology, Fallon Clinic, Worcester, MA, USA
  3. Division of Ophthalmology, Fallon Clinic, Worcester, MA, USA
  4. Immunology and Uveitis Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School. Boston, MA, USA
  1. ROBERT A YOOD
  1. Immunology and Uveitis Service, Department of Ophthalmology. Massachusetts Eye and Ear Infirmary, Harvard Medical School. Boston, MA, USA
  2. Division of Rheumatology, Fallon Clinic, Worcester, MA, USA
  3. Division of Ophthalmology, Fallon Clinic, Worcester, MA, USA
  4. Immunology and Uveitis Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School. Boston, MA, USA
  1. THOMAS J CONDON
  1. Immunology and Uveitis Service, Department of Ophthalmology. Massachusetts Eye and Ear Infirmary, Harvard Medical School. Boston, MA, USA
  2. Division of Rheumatology, Fallon Clinic, Worcester, MA, USA
  3. Division of Ophthalmology, Fallon Clinic, Worcester, MA, USA
  4. Immunology and Uveitis Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School. Boston, MA, USA
  1. C STEPHEN FOSTER
  1. Immunology and Uveitis Service, Department of Ophthalmology. Massachusetts Eye and Ear Infirmary, Harvard Medical School. Boston, MA, USA
  2. Division of Rheumatology, Fallon Clinic, Worcester, MA, USA
  3. Division of Ophthalmology, Fallon Clinic, Worcester, MA, USA
  4. Immunology and Uveitis Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School. Boston, MA, USA
  1. C Stephen Foster, MD, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA.

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Editor,—A 35-year-old white man was referred with a 1 month history of recurrent bilateral uveitis.

The patient had a history of cyclic neutropenia beginning at age 19. Severe neutropenia (total neutrophil count as low as 68 cells × 106/l), lasting about 3 days, was documented to occur at the time of clinical symptoms. Prednisone produced a marked diminution in episodes of symptomatic neutropenia.

At age 35, the patient developed iritis in his left eye during a ‘crisis’. This was treated with 0.1% dexamethasone phosphate solution. The anterior chamber inflammatory reaction subsided, but 1+ cells persisted in the vitreous despite an injection of methylprednisolone 40 mg into the sub-Tenon’s capsule. The fundus was normal. An extensive immunological examination and HLA-B27 determination were negative or normal. The uveitis resolved as the crisis subsided. Recurrent episodes of uveitis in the left eye occurred episodically, but always at the time of neutropenic crisis and despite topical and systemic anti-inflammatory therapy.

Development of cataract reduced the visual acuity to counting fingers at 1 foot. Cataract extraction with posterior chamber lens implantation resulted in stable visual acuity of 20/30 (5 year follow up) despite continued episodes of iritis.

COMMENT

Cyclic neutropenia is a rare disorder characterised by regular oscillations in blood neutrophil counts, as well as other blood cells.1 Cycling occurs regularly every 21 days and lasts 3–6 days in most of the cases.2-4 The patient described here presented with cyclic episodes of neutropenia occurring every 18–25 days and lasting for 3–5 days. The patient’s neutrophil counts were repeatedly below 800 cells × 106/l at the lowest and no changes in other leucocyte or platelet counts were observed.

During neutropenic episodes, patients may experience a wide variety of symptoms, from malaise and low grade fever to severe life threatening gastrointestinal infections and, although there is moderate morbidity associated with the disease, its course is usually benign.5 Conjunctivitis has been described.1Iridocyclitis associated with neutropenic cycling and refractory to therapy has not been described previously. Extensive and repeated laboratory investigations for an underlying cause of the uveitis in our patient were negative except for large granular lymphocytes and an IgG antineutrophil antibody, both characteristic of cyclic neutropenia.

Many therapeutic strategies have been used in the management of patients with cyclic neutropenia. Splenectomy, testosterone, etiocholanolone, and endotoxin have been employed, all to some therapeutic effect.6 The response to alternate day low dose prednisone therapy has been particularly successful for patients with the adult onset of the disease.6 Our patient was managed with 5–25 mg of prednisone every other day, with significantly reduced symptomatology and neutrophil cycling. More recently, correction has been reported with granulocyte macrophage-colony stimulating factor (GM-CSF)7 and granulocyte-colony stimulating factor (G-CSF).8 Although a direct cause-effect association between the recurrent uveitis present in this patient and adult onset cyclic neutropenia cannot be definitively established, the existence of different immune system abnormalities (for example, proliferation of large granular lymphocyte cells, inversion of the CD4:CD8 ratio, presence of different autoantibodies) in patients with cyclic neutropenia and large granular lymphocytosis may contribute to the recurrence of uveitis and its refractoriness to conventional therapy.

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