Sweat gland morphology and periglandular innervation in essential palmar hyperhidrosis before and after treatment with intradermal botulinum toxin

Background: Intradermal botulinum toxin (Btx) produces long-lasting relief of focal hyperhidrosis, but its mechanism of action is poorly understood. Objective: To study the effect of Btx A on the size and innervation of sweat glands in patients with palmar hyperhidrosis. Methods: Palmar skin biopsy was performed in 26 hyperhidrotic patients before scheduled Btx treatment and in 11 controls. Twelve of the patients also underwent biopsy 1 to 6 months after the Btx injections. Sweat gland morphology was investigated by light microscopy; the cross-sectional area of the secretory tubule and its lumen was measured by image analysis. Immunofluorescence (IF) with antibodies to the neural markers protein gene product 9.5 (PGP 9.5) and growth-associated protein 43 (GAP 43), and to vasoactive intestinal pepticle (VIP) and calcitonin gene-related peptide (CGRP), was used to analyze the periglandular innervation. Results. The gross morphology of the sweat glands was similar in patients and controls, with no significant differences in tubular and luminal areas between the groups. After Btx treatment, the tubular dimensions remained unchanged, but the lumen tended to be smaller (P = .07). Around the glands, increased GAP 43 staining indicating sprouting was seen within 3 months after Btx treatment (P = .016); whereas the PGP 9.5 staining was decreased in most specimens (P = .09) indicating lack of functional nerve growth. No change in VIP or CGRP immunoreactivity was observed. Conclusions. The sweat glands appear structurally normal in hyperhidrotic patients before Btx therapy, whereas after therapy the luminal area of the gland is frequently diminished. The IF data GAP 43/PGP 9.5 suggest that Btx therapy induces long-standing functional denervation of the sweat glands, which might explain its anti-transpiratory efficacy.