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Published on: June 25, 2019
Immunostaining of skin biopsy adds no diagnostic value in MGUS-associated peripheral neuropathy
Ali Al-Zuhairy1, Henrik Daa Schrøder2, Torben Plesner3
1Department of Neurology, Odense University Hospital, Odense, Denmark.
Background And Purpose:
For several decades an association between MGUS, IgM-MGUS in particular, and peripheral neuropathy has been suspected. Several histopathology studies have shown binding of IgM to myelin and a secondary widening of myelin lamellae in cutaneous nerves and in the sural nerve of patients with IgM-MGUS, or Waldenström's Macroglobulinaemia (WM), and peripheral neuropathy. In this retrospective study we investigated the value of skin biopsy examination in the diagnosis of MGUS- and WM-associated peripheral neuropathy.
Methods:
A total of 117 patients, who were examined for an M-component in serum with associated nerve symptoms, had a skin biopsy taken and examined for immunoglobulin deposition in cutaneous nerves. Thirty-five patients were diagnosed with MGUS or WM and peripheral neuropathy with no other cause of neuropathy. Nineteen patients had MGUS but no peripheral neuropathy.
Results:
Of the 35 patients with MGUS or WM and peripheral neuropathy, four had immunoglobulin deposition in the skin biopsy, all of whom had an IgM gammopathy. In the control group of 19 without peripheral neuropathy, three had immunoglobulin deposition in the skin biopsy, all of whom had IgM-MGUS. In both groups, there was a trend towards higher IgM blood levels in patients with immunoglobulin deposition. Half of the patients with IgM gammopathy in the neuropathy group had anti-MAG reactivity, whereas only one in the control group had weak anti-MAG reactivity.
Conclusion:
Our study indicates that examination of skin biopsies for immunoglobulin deposition does not add significant diagnostic value in the evaluation of neuropathies suspected to be caused by MGUS or WM. IgM immunoglobulin deposition in skin biopsy might merely be an epiphenomenon secondary to high IgM blood levels.
Insights
Skin biopsy examination for immunoglobulin deposition is not a valuable diagnostic tool for identifying peripheral neuropathy associated with monoclonal gammopathy of undetermined significance (MGUS) or Waldenström's macroglobulinaemia (WM). Findings suggest IgM deposition may be secondary to high IgM levels.
Area of Science:
- Neurology
- Immunology
- Pathology
Background:
- An association between monoclonal gammopathy of undetermined significance (MGUS), particularly IgM-MGUS, and peripheral neuropathy has been long suspected.
- Histopathology studies show IgM binding to myelin in patients with IgM-MGUS or Waldenström's macroglobulinaemia (WM) and neuropathy.
Purpose of the Study:
- To investigate the diagnostic value of skin biopsy examination for immunoglobulin deposition in MGUS- and WM-associated peripheral neuropathy.
Main Methods:
- Retrospective study of 117 patients with M-component and nerve symptoms.
- Skin biopsies examined for immunoglobulin deposition in cutaneous nerves.
- Patients categorized into groups with and without neuropathy, with confirmed MGUS or WM.
Main Results:
- Only 4 of 35 patients with MGUS/WM and neuropathy showed immunoglobulin deposition, all IgM.
- 3 of 19 controls without neuropathy had IgM deposition, all with IgM-MGUS.
- A trend towards higher IgM levels in patients with deposition was observed; anti-MAG reactivity was more common in the neuropathy group.
Conclusions:
- Skin biopsy for immunoglobulin deposition offers no significant diagnostic value for MGUS/WM-associated neuropathies.
- IgM deposition in skin biopsies may be an epiphenomenon of elevated IgM levels.
