Clinicopathological digital image analyses before and after thermal stimulation subdivide acquired idiopathic generalized anhidrosis into inflammatory and non-inflammatory type


      • Inflammation in acquired idiopathic generalized anhidrosis (AIGA) is variable.
      • Extent of cell infiltration can be affected by thermal stimulation.
      • Immune privilege of the sweat duct is impaired in inflammatory AIGA.
      • Ductal dysfunction is suggested in non-inflammatory AIGA.
      • Improvement of AIGA is digitally assessed to identify correlating factors.



      Acquired idiopathic generalized anhidrosis (AIGA) manifests varying degrees of syringotropic inflammation.


      To better understand the basis of inflammation in AIGA.


      Changes in the extent of cell infiltration around the sweat gland/duct and the difference in the expression level of immune privilege (IP)-related/sweat gland markers before and after thermal stimulation were assessed in AIGA. We also adopted a semi-quantitative digital image analysis of sweating as detected by the starch-iodine method. The changes in sweating before and after treatment was defined as the improvement index.


      Nine AIGA cases were analyzed. Two cases with minimal inflammation were defined as non-inflammatory type (non-inf)AIGA, while others with evident cell infiltration were defined as inflammatory type (inf)AIGA. MHC class I was significantly upregulated with downregulation of macrophage migration inhibitory factor and alpha-melanocyte-stimulating hormone exclusively in the sweat duct of infAIGA after thermal stimulation (p < 0.05). Furthermore, the extent of inflammation and the ductal dermcidin expression prior to thermal stimulation were inversely correlated (r = − 0.807), while that and the ductal claudin-1 expression after thermal stimulation was positively correlated (r = 0.875). The improvement index positively correlated with the degree of inflammation after thermal stimulation implying possible contribution of inflammation in AIGA pathophysiology. In addition, interferon-induced protein 10 and claudin-1 expression level in the sweat duct before thermal stimulation respectively correlated with the improvement index (r = 0.750, and 0.762).


      The pathophysiology of AIGA may be subcategorized into two groups: IP-collapse possibly play some roles in infAIGA, while ductal dysfunction may exist in non-infAIGA.


      AChR M3 (muscarinic acetylcholine receptor M3), AIGA (acquired idiopathic generalized anhidrosis), α-MSH (alpha-melanocyte-stimulating hormone), BI (brightness index), CXCR3 (C-X-C motif chemokine receptor 3), IFN-γ (interferon-gamma), IP (immune privilege), IP-10 (interferon gamma-induced protein 10), DCD (dermcidin), MHC (major histocompatibility complex), MIF (macrophage migration inhibitory factor), SI (sweating index), SwD (sweat duct), SwG (sweat gland)


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