Ross Syndrome

ABSTRACT

Ross syndrome is a rare disorder of thermoregulation and includes a triad of tonic pupil, anhidrosis/hypohidosis and areflexia. Here we describe one such case in a 40-year-old woman. A general awareness among physicians, dermatologists and ophthalmologists regarding this disease can alleviate unnecessary anxiety and avoid unnecessary investigations.

Case

A 40-year-old woman presented with a burning sensation on the left half of her body during the summer and anisocoria. There was no history of trauma, surgery, syncopal attacks or any other illness. There was no contributory family history. Her unaided distance visual acuity was 20/20 (Snellen) in each eye and her near vision was N6 in each eye with +1.0 D glasses. Her colour vision was normal. External examination of the eyes, eyelid position and extraocular movements were normal. Anterior segment examination showed anisocoria with the left pupillary diameter being 4 mm and the right 2 mm in bright light. The direct and consensual light reflexes were absent in the left eye and normal in the right eye (Figure 1a). However, the near reflex was present in both eyes (Figure 1b) with a dilatation lag of the left pupil. Posterior segment examination was normal in both eyes.

Figure 1.

(a) Clinical photograph showing anisocoria in the light (the left pupil did not constrict to light). (b) Left pupillary constriction seen on near reflex.

Her general condition was normal and her vital signs were stable. Cutaneous examination showed decreased sweating over the face, neck, upper back and arms (patchy areas of hypohidrosis and anhidrosis) on both sides. An iodine-starch test (thermoregulatory sweat test) confirmed this observation (Figure 2). There was no sensory disturbance or enlarged peripheral nerves. All of the deep tendon reflexes in the arms and legs were absent bilaterally. There was no response to Jendrassik manoeuvre. Examination of other organ systems was normal. Orthostatic hypotension was absent and the cardiovascular reflexes (heart rate and blood pressure responses to Valsalva manoeuvre and analysis of heart rate variability on electrocardiogram) were normal. Laboratory investigations including complete blood count, thyroid function tests, blood gluocose and MRI of the brain and spine were normal.

Figure 2.

Iodine-starch test of the upper back showing complete absence of staining on the left (indicating anhidrosis) (asterisk) and patchy staining on the right (indicating patchy areas of intact sweating) (arrowhead).

Discussion

Unilateral dilatation of the pupil is often a subject of anxiety to clinicians. Patients are subjected to unnecessary, expensive tests and referrals. Some of the causes of unilateral dilatation of the pupil include third nerve palsy, traumatic mydriasis, post cataract surgery mydriasis, pharmacological mydriasis and tonic pupils. Both light and near reflexes are abnormal in all of the above conditions except in a tonic pupil. Our patient had light-near dissociation (the abnormal pupil did not constrict to direct and consensual light but did to near reflex) with dilatation lag of the left pupil, which pointed towards a tonic pupil. The triad of tonic pupil, anhidrosis/hypohidosis and areflexia are seen in a very rare disorder of thermoregulation called Ross syndrome.¹

The first case of Ross syndrome was described by Ross in 1958.² Ever since there have been only a handful of cases reported worldwide. Some believe this to be a combination of two separate syndromes namely Harlequin syndrome and Holmes-Adie syndrome.³ Recent evidence suggests a decrease in sudomotor, vasomotor and pilomotor innervation in the skin of patients with Ross syndrome.^4–6 Hence, there is a lack of sweating and cutaneous vasoregulation leading to heat intolerance. The iodine-starch test helps to demarcate areas of intact sweating and anhidrotic areas. Areas of intact sweating stain positive.⁷ Our patient showed no staining on the left side of her back and had patchy staining on the right side of her back (Figure 2). Tonic pupil results from damage to the ciliary ganglion or postganglionic parasympathetic nerve fibres.⁸ The exact cause of areflexia has not been found. Some postulate damage to the dorsal roots, sensory ganglia or the afferent fibres in the spinal cord.^9,10 Tonic pupil may be present unilaterally or bilaterally and areflexia may be generalised. The tonic pupil shows a hypersensitivity response to dilute pilocarpine drops and this may be performed to confirm the diagnosis of postganglionic parasympathetic denervation hypersensitivity.¹¹ The exact pathogenesis of the autonomic ganglion damage is uncertain but it is postulated that there is a congenital lack of factors that promote the survival of these neurons leading to their apoptosis. Some studies have suggested an autoimmune basis for the disease with some patients testing positive for different antibodies like anti-nuclear (ANA), SSA, SSB and anti-thyroid antibodies.^12,13 Nolano et al. showed that this condition is progressive but benign.⁶

The differential diagnoses to be considered in such patients include Holmes-Adie syndrome (tonic pupil with absent knee/ankle jerks), Horner syndrome (miosis with anhidrosis, deep tendon reflexes are normal) and other causes of anhidrosis like Harlequin syndrome, hereditary sensory and autonomic neuropathy, diabetes mellitus, leprosy and other polyneuropathies (pupils and deep tendon reflexes are usually normal).¹⁴

Although anhidrosis impairs the quality of life of these patients, most learn ways of avoiding excessive heating of the body by adopting simple measures like avoiding excess heat and wearing wet clothes during strenuous physical activity.

A general awareness among physicians, dermatologists and ophthalmologists regarding this disease can alleviate unnecessary anxiety and avoid unnecessary investigations.

Declaration of interest

The authors report no conflict of interest