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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 4  |  Issue : 1  |  Page : 57-60

Ross syndrome and diabetes mellitus: An interesting association


Department of Skin and VD, SBH Government Medical College, Dhule, Maharashtra, India

Date of Submission10-Aug-2018
Date of Decision21-Nov-2018
Date of Acceptance06-Dec-2018
Date of Web Publication06-Jan-2020

Correspondence Address:
Chetan D Rajput
Department of Skin and VD, SBH Government Medical College, Chakkarbardi, Dhule - 424 002, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CDR.CDR_33_18

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  Abstract 


Ross syndrome is a rare disorder of sweating with a triad of segmental anhidrosis, tonic pupil, and hyporeflexia. Survey of available literature shows scarce reporting of such cases globally and countable number of cases from India. Here, we report the case of a 35-year-old male presented with heat intolerance and all three clinical features of Ross syndrome. Further investigations revealed him to be diabetic. Diabetes was treated with insulin and oral hypoglycemics. The patient had increased comfort in hot and humid climate and slight improvement in sweating over anhidrotic areas after strict diabetic control. The association of diabetes mellitus and Ross syndrome in the index case is quite interesting and hitherto not reported.

Keywords: Anhidrosis, diabetes, hyporeflexia, Ross syndrome, tonic pupil


How to cite this article:
Rajput CD, Gore SB, Malani SS, Shah SM. Ross syndrome and diabetes mellitus: An interesting association. Clin Dermatol Rev 2020;4:57-60

How to cite this URL:
Rajput CD, Gore SB, Malani SS, Shah SM. Ross syndrome and diabetes mellitus: An interesting association. Clin Dermatol Rev [serial online] 2020 [cited 2020 Jan 27];4:57-60. Available from: http://www.cdriadvlkn.org/text.asp?2020/4/1/57/275244




  Introduction Top


Ross described for the first time a case of tonic pupil and areflexia of the lower extremities and segmental hypohidrosis.[1] In Ross syndrome, progressive anhidrosis, compensatory hyperhidrosis, and heat intolerance are presenting features along with Holmes–Adie syndrome (tonic pupil and hyporeflexia). The absence of cutaneous vasoactive intestinal polypeptide-immunoreactive nerve (VIP-ir) fibers explains the thermoregulatory dysfunction in Ross patients.[2] There is no effective therapeutic management for this condition. Various treatment modalities for compensatory hyperhidrosis include iontophoresis, botulinum toxin, topical glycopyrrolate and avoidance of sun exposure, wet clothing in hot conditions along with treatment of underlying cause if any. Here, we report a case of previously undiagnosed diabetic patient presented as Ross syndrome and was improved slightly after treatment of diabetes.


  Case Report Top


A 35-year-old male presented with heat intolerance and absence of sweating over various body areas for 2 years. The patient used to work continuously in hot environment for 6–7 h, but for the past 2 years, he developed intolerance to sun exposure with flushing over the face and extremities and worsening of these symptoms over this period. He also noticed loss of sweating over the right arm, then over the right side of the face, dorsum of both feet and left thigh, and hyperhidrosis over other body areas in segmental distribution. For the past 1 month, he had malaise and discomfort while working in hot and humid condition. Other symptoms such as fever, palpitation, and syncope were not present. There was no obvious history of hypertension, diabetes, or thyroid disorder in the past as well as in his family.

General examination was within normal limits. Cutaneous examination revealed the absence of sweating over the right half of the face [Figure 1], right arm and forearm, lateral aspect of the left thigh, and dorsum of both feet in segmental distribution with erythema over these areas after exercise [Figure 2]. Anhidrosis was confirmed by starch–iodine test [Figure 3]. Systemic examination was within normal limit, but knee and ankle jerk were sluggish.
Figure 1: Anhidrosis over the right side of the forehead

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Figure 2: Anhidrosis and erythema over the right forearm

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Figure 3: Starch–iodine test. Color change over hidrotic area (left). No color change on anhidrotic area (right)

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A diagnosis of acquired progressive segmental anhidrosis was made. Routine hematological and biochemical investigations were performed. The fasting and postprandial blood sugar levels along with glycosylated hemoglobin (HbA1c) were markedly raised (fasting blood sugar – 240 mg/dL; postprandial blood sugar – 310 mg/dL; and HbA1c – 8.3%). Skin biopsy with hematoxylin and eosin stain from an anhidrotic area showed perieccrine lymphocytic infiltrate around some eccrine unit while few showed complete obliteration by fibroplasias [Figure 4].
Figure 4: (a) Biopsy from an anhidrotic area (H and E, scanner view). (b) Anhidrotic area showing perieccrine lymphocytic infiltrate around some eccrine unit while few showed complete obliteration by fibroplasias (H and E, ×100)

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The patient was then examined by an ophthalmologist and neurologist. He did not have headache while reading; however, ophthalmological examination revealed anisocoria with segmental retraction of the left pupil and dilated right pupil [Figure 5]. The right pupil was reacting sluggishly to light [Figure 6]. Both pupils got contracted after adding pilocarpine drops. The spine was absolutely normal on examination. X-ray spine and magnetic resonance imaging brain and spine were normal. Further investigations such as ECG, antinuclear antibody blot test, anti hepatitis C virus antibodies, venereal disease research laboratory, and ELISA for HIV were negative.
Figure 5: Anisocoria with segmental retraction of the left pupil and dilated right pupil

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Figure 6: Right pupil reacting sluggishly to light

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The case was diagnosed as Ross syndrome associated with diabetes mellitus. Diabetes was treated with insulin and oral hypoglycemics. Hyperhidrosis was treated with 20% aluminum chloride. The patient had increased comfort in hot and humid climate and slight improvement in sweating over anhidrotic areas after strict diabetic control.


  Discussion Top


Ross syndrome is a rare disorder of sweating, with very few cases being reported, but Nolano et al. observed 12 patients with Ross syndrome in 5 years and raised question about rarity of this condition and probability of its underdiagnosis.[2] Survey of available literature shows countable number of cases from India. Details of these cases with unusual associations are summarized in [Table 1].[3],[4],[5] Exact etiopathogenesis of this syndrome is unknown. An underlying apoptotic process involving the neurons derived from neural crest could be the cause.[6] However, a few authors opined that microvascular ischemia [7] and autoimmunity have a role.[8]
Table 1: Ross syndrome cases reported from India

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Diabetes can cause various neuropathies by affecting different parts of nervous system, leading to diverse clinical manifestations. Sensorimotor distal symmetrical polyneuropathy and autonomic neuropathies are the most common neuropathies.[9] Sympathetic dysfunction such as redistribution of pseudomotor responses and pupillary light reflexes can be detected very early in type 1 diabetes.[10] Various hypotheses for diabetic neuropathies include hyperglycemia causing activation of polyol pathway and accumulation of sorbitrate causing direct and ischemic nerve damage, microvascular ischemia due to vasoconstriction by activation of protein kinase c, free radical-induced endothelial damage, excess nitroactive stress, autoantibodies to autonomic nerves, reduction in neurohormonal growth factors, and deficiency of essential fatty acids.

Thus, Ross syndrome and diabetic neuropathy share some common etiopathological factors. Diabetic sensorimotor distal symmetrical polyneuropathy can lead to hyporeflexia in lower extremity while autonomic neuropathy as a result of postganglionic sympathetic cholinergic fiber damage can lead to third cranial neuropathy causing tonic pupil and pseudomotor dysfunction causing segmental anhidrosis. In this case, we hypothesized that either uncontrolled diabetes could have exacerbated the already existing Ross syndrome or various diabetic neuropathies led to presentation of Ross syndrome as explained in the flowchart [Figure 7]. Further, improvement after antidiabetic treatment supports this hypothesis.
Figure 7: Diabetic neuropathies and Ross syndrome association

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  Conclusion Top


Segmental anhidrosis, hyporeflexia, and tonic pupil were often found separately in diabetic patients. However, the presence of all these features in the same patient of diabetes mellitus as Ross syndrome is being reported for the first time. This case brings attention to the interesting association between diabetes, a common condition, and Ross syndrome, a rare one.

Acknowledgment

We would like to thank Dr. Arun C, Inamdar, Professor and Head, Department of SBMP, Medical College and Hospital, BLDE University, Bijapur, for guidance about writing manuscript.

Declaration of patient consent

The informed consent was obtained for participation in the study and publication of data and images for research and educational purposes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ross AT. Progressive selective sudomotor denervation; a case with coexisting Adie's syndrome. Neurology 1958;8:809-17.  Back to cited text no. 1
    
2.
Nolano M, Provitera V, Perretti A, Stancanelli A, Saltalamacchia AM, Donadio V, et al. Ross syndrome: A rare or a misknown disorder of thermoregulation? A skin innervation study on 12 subjects. Brain 2006;129:2119-31.  Back to cited text no. 2
    
3.
Agarwala MK, George L, Parmar H, Mathew V. Ross syndrome: A case report and review of cases from India. Indian J Dermatol 2016;61:348.  Back to cited text no. 3
[PUBMED]  [Full text]  
4.
Sharma MK, Gupta S, Yadav S, Kumar R. A rare case of Ross syndrome. Indian Dermatol Online J 2017;8:370-2.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Chandramouleeswaran V, Sindhuja L, Ramya R, Kannan V. Ross syndrome: A case report. Neurol Asia 2018;23:101-3.  Back to cited text no. 5
    
6.
Coulson IH. Disorders of sweat glands. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook's Textbook of Dermatology. 8th ed., Vol. 44. West Sussex: Wiley Blackwell Publishers; 2010. p. 13-4.  Back to cited text no. 6
    
7.
Kalapesi FB, Krishnan AV, Kiernan MC. Segmental facial anhidrosis and tonic pupils with preserved deep tendon reflexes: A novel autonomic neuropathy. J Neuroophthalmol 2005;25:5-8.  Back to cited text no. 7
    
8.
Vasudevan B, Sawhney M, Vishal S. Ross syndrome with ANA positivity: A clue to possible autoimmune origin and treatment with intravenous immunoglobulin. Indian J Dermatol 2010;55:274-6.  Back to cited text no. 8
[PUBMED]  [Full text]  
9.
Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, et al. Diabetic neuropathies: A statement by the American Diabetes Association. Diabetes Care 2005;28:956-62.  Back to cited text no. 9
    
10.
Cardone C, Dyck PJ. A neuropathic deficit, decreased sweating, is prevented and ameliorated by euglycemia in streptozocin diabetes in rats. J Clin Invest 1990;86:248-53.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
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