LP-10. Paraprotein associated polyneuropathy: A case series

Summary

Dysimmune paraprotein-associated polyneuropathies (DPAP) are a group of diseases with different courses. The period from initial complaints to clinical verification, due to the rarity of the diagnosis, may take a long time. Standard first-line therapy for demyelination includes glucocorticosteroids; second-line therapy has not been specified. Our aim was to rise alertness of the medical community about the peculiarities of diagnosis and treatment of patients with DPAP.

Materials and methods

We performed a retrospective analysis of DPAP cases. Axonal (ADPAP) or demyelinating (DDPAP) type of polyneuropathy was diagnosed on the basis of electroneuromyographic study, according to the criteria of European Academy of Neurology and Peripheral Nerve Society adopted in 2021. In small-fiber ADPAP, the diagnosis was specified by quantitative sensory testing. Immunosuppressive/modulatory treatment included plasmapheresis for at least three weeks, prednisolone 1 mg/kg/day for at least two weeks, rituximab once every 6 months for up to 2 years (375 mg/m², 4 weekly injections or 2 be-weekly injections of 1000 mg/m²), intravenous immunoglobulin 2 g/kg, then 1 g/kg monthly injections to maintain clinical response, and azathioprine 1-3 mg/day for at least one month. The therapy was considered effective in case of neurological improvement.

Results

We analyzed clinical data of 16 patients with DPAP (8 males and 8 females. Median age at the disease onset was 57 years (41-88), and their age at diagnosis was 60 (49-88) years. The median paraprotein concentration was 4.03 (0.17-26.7) g/L. Immunochemical variants and the pattern of neural affection are listed in Table 1.

All patients received symptomatic analgesic therapy with GABA analogs. Patients with a predominantly demyelinating pattern received specific treatment. In a small-group analysis, rituximab showed higher efficacy in the DDPAP treatment compared with glucocorticosteroids. The general characteristics of therapy and its efficacy are summarized in Table 2.

Three patients (ADPAP, n=2 and DDPAP, n=1) were diagnosed with smoldering multiple myeloma. A single patient with smoldering myeloma and DDPAP received antitumor therapy with lenalidomide, daratumumab and dexamethasone along with intravenous immunoglobulin treatment. A persistent neurologic improvement without any correlation with paraprotein concentration shifts was observed. At a median follow-up of 15 (1-132) months, 4 (25%) patients died from subarachnoid hemorrhage (n=1), progressive neurologic worsening (n=2) and pulmonary embolism (n=1).

Conclusion

The ADPAP is more common in the presented group of DPAP. The time from onset of symptoms to verification of the diagnosis may take several years. Paraprotein was more often represented by immunoglobulins M and G, but kappa-chain clonality predominates. When analyzing small groups of patients with DDPAP, the efficacy of glucocorticosteroids was confirmed, but better efficacy was found for rituximab. Further studies are needed to determine the optimal treatment.

Keywords

Paraproteinaemia, immunochemical variants, polyneuropathy, treatment.