Cytological vitreous findings in a patient with infantile neurological cutaneous and articular (CINCA) syndrome

BACKGROUND

The chronic infantile neurological cutaneous and articular (CINCA) syndrome is a rare inflammatory paediatric disease identified by Prieur et al in 1987.1 Ocular manifestations have been observed in 26% of patients2 and include anterior uveitis, abnormal optic disc appearance and posterior inflammation with vitritis and vasculitis.3 This article describes cytological vitreous findings, obtained by pars plana vitrectomy, in patients with CINCA syndrome.

CASE PRESENTATION

A 1-month-old boy was initially examined because of a bilateral anterior uveitis for 10 days. He was born after a normal pregnancy. On the second day, however, a generalised urticaria was observed and his serum C reactive protein level was raised. He presented with recurrent fever, leucocytosis, neutrophilia, increased erythrocyte sedimentation rate and raised serum level of immunoglobin (Ig)G. No evidence of infection was found, but hepatosplenomegaly was observed. At the same time arthritis developed, involving the knees, elbows and ankles. Neurological findings included chronic meningitis, and the patient’s development was markedly delayed.

Anterior-segment examination showed two positive cells in the anterior chamber without posterior iris synechias. Funduscopy showed three positive denses vitreous cells that prevented the fundus of the eye being seen in both eyes. Topical steroids and mydriatics were initiated with high-dose intravenous methylprednisolone for 3 days followed by oral prednisone (0.5 mg/kg body weight/day). As no response to treatment was observed, a three-port pars plana vitrectomy was performed in the patient’s right eye. During surgery, denses vitreous cells were observed with white infiltrates over the retina, optic nerve and pars plana (fig 1). Cytological examination of the vitrectomy specimen showed abundant cellularity, with a small number of polymorphonuclear leucocytes and lymphocytes and a dominant population of larger cells with wide, vacuolated cytoplasm and reniform nuclei with bland chromatin (fig 2A). Immunocytochemistry using a CD68 antibody was diffusely positive, confirming their macrophagic nature (fig 2B). Other diagnostic possibilities, such as granulomatous infections, xanthogranulomatous inflammation, metabolic storage disease, Whipple’s disease and Langerhans cell hystiocytosis were ruled out. The CINCA syndrome was established as a result of the clinical and pathological findings. To decrease steroidal side effects, ciclosporin A (5 mg/kg/day) was added with no clinical benefits. The patient finally died at the age of 2 years.

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Figure 1 Ophthalmoscopical view during pars plana vitrectomy.

The dense vitreous cells, and whitish deposits over the retina, pars plana and optic nerve are evident.

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Figure 2 (A) Cytological smear of vitreous fluid: numerous histiocytes with bland nuclei and wide cytoplasm (May-Grunwald-Giemsa, 400×).

(B) Immunocytochemistry in vitreous fluid: strong and diffuse cytoplasmatic positivity with the monocyte/macrophage marker CD68.

DISCUSSION

The CINCA syndrome is an inflammatory disease characterised by persistent rash and chronic aseptic meningitis, with extensive infiltration of polymorphonuclear and macrophage cells at the sites of inflammation.4 The CINCA syndrome belongs to the group of systemic autoinflammatory diseases characterised by episodic or fluctuating degrees of inflammation, without evidence of high-titre autoantibodies or antigen-specific T cells. The disease is caused by mutations in the CIAS1 gene that encodes a protein cryopyrin, NALP3 or PYPAF1.5 Mutations in cryopyrin have a profound pro-inflammatory effect. Cryopyrin is a caspase 1 activator, which in turn causes the activation of interleukin (IL)1ß. The activating mutations of cryopyrin induce an excessive activation of IL1ß, which causes an influx of macrophages and polymorphonuclear cells to the site of inflammation, in our patient, in his eye.6

We could not find any reference to previous pathological descriptions of the cell composition of the vitreous fluid in the CINCA syndrome. Only scattered reports on this entity contain pathological descriptions of skin and liver biopsy specimens, with unspecific inflammatory infiltrates composed of lymphocytes, neutrophils and eosinophils. However, current knowledge about the nature of this syndrome, which seems to be a phagocytic cell mediated autoinflammatory disease, raises the possibility that the macrophagic infiltrate could be the hallmark of the disease, at least in the vitreous fluid.