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

      Highlights

      • 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.

      Abstract

      Background

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

      Objective

      To better understand the basis of inflammation in AIGA.

      Methods

      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.

      Results

      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).

      Conclusion

      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.

      Abbreviations:

      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)

      Keywords

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      References

        • Ohshima Y.
        • Yanagishita T.
        • Ito K.
        • Tamada Y.
        • Nishimura N.
        • Inukai Y.
        • et al.
        Treatment of patients with acquired idiopathic generalized anhidrosis.
        Br. J. Dermatol. 2013; 168: 430-432
        • Munetsugu T.
        • Fujimoto T.
        • Oshima Y.
        • Sano K.
        • Murota H.
        • Satoh T.
        • et al.
        Revised guideline for the diagnosis and treatment of acquired idiopathic generalized anhidrosis in Japan.
        J. Dermatol. 2017; 44: 394-400
        • Satoh T.
        Clinical analysis and management of acquired idiopathic generalized anhidrosis.
        Curr. Probl. Dermatol. 2016; 51: 75-79
        • Ando Y.
        • Fujii S.
        • Sakashita N.
        • Uchino M.
        • Ando M.
        Acquired idiopathic generalized anhidrosis: clinical manifestations and histochemical studies.
        J. Neurol. Sci. 1995; 132: 80-83
        • Fujita K.
        • Hatta K.
        Acquired generalized anhidrosis: review of the literature and report of a case with lymphocytic hidradenitis and sialadenitis successfully treated with cyclosporine.
        Dermatology. 2013; 227: 270-277
        • Iwama E.
        • Fujimura T.
        • Tanita K.
        • Ishibashi M.
        • Watabe A.
        • Aiba S.
        Acquired idiopathic generalized anhidrosis: an immunohistopathological investigation of peri-glands infiltrated with immunoreactive cells.
        Acta Derm. Venereol. 2015; 95: 743-744
        • Ito T.
        • Ito N.
        • Bettermann A.
        • Tokura Y.
        • Takigawa M.
        • Paus R.
        Collapse and restoration of MHC class-I-dependent immune privilege: exploiting the human hair follicle as a model.
        Am. J. Pathol. 2004; 164: 623-634
        • Galea I.
        • Bechmann I.
        • Perry V.H.
        What is immune privilege (not)?.
        Trends Immunol. 2007; 28: 12-18
        • Ito T.
        Recent advances in the pathogenesis of autoimmune hair loss disease alopecia areata.
        Clin. Dev. Immunol. 2013; 2013348546
        • Meyer K.C.
        • Klatte J.E.
        • Dinh H.V.
        • Harries M.J.
        • Reithmayer K.
        • Meyer W.
        • et al.
        Evidence that the bulge region is a site of relative immune privilege in human hair follicles.
        Br. J. Dermatol. 2008; 159: 1077-1085
        • Paus R.
        • Ito N.
        • Takigawa M.
        • Ito T.
        The hair follicle and immune privilege.
        J. Invest. Dermatol. Symp. Proc. 2003; 8: 188-194
        • Shimoda-Komatsu Y.
        • Yamazaki Y.
        • Tsukashima A.
        • Kimishima M.
        • Ohyama M.
        Digital immunohistological dissection of immune privilege collapse in syringotropic autoimmune diseases: implication for the pathogenesis.
        J. Dermatol. Sci. 2021; 101: 30-39
        • Schittek B.
        • Hipfel R.
        • Sauer B.
        • Bauer J.
        • Kalbacher H.
        • Stevanovic S.
        • et al.
        Dermcidin: a novel human antibiotic peptide secreted by sweat glands.
        Nat. Immunol. 2001; 2: 1133-1137
        • Rieg S.
        • Steffen H.
        • Seeber S.
        • Humeny A.
        • Kalbacher H.
        • Dietz K.
        • et al.
        Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo.
        J. Immunol. 2005; 174: 8003-8010
        • Kurzen H.
        • Berger H.
        • Jager C.
        • Hartschuh W.
        • Naher H.
        • Gratchev A.
        • et al.
        Phenotypical and molecular profiling of the extraneuronal cholinergic system of the skin.
        J. Invest. Dermatol. 2004; 123: 937-949
        • Yamaga K.
        • Murota H.
        • Tamura A.
        • Miyata H.
        • Ohmi M.
        • Kikuta J.
        • et al.
        Claudin-3 loss causes leakage of sweat from the sweat gland to contribute to the pathogenesis of atopic dermatitis.
        J. Invest. Dermatol. 2018; 138: 1279-1287
        • Shimoda-Komatsu Y.
        • Sato Y.
        • Yamazaki Y.
        • Takahashi R.
        • Shiohara T.
        A novel method to assess the potential role of sweating abnormalities in the pathogenesis of atopic dermatitis.
        Exp. Dermatol. 2018; 27: 386-392
        • Tokura Y.
        Direct and indirect action modes of acetylcholine in cholinergic urticaria.
        Allergol. Int. 2021; 70: 39-44
        • Kageyama R.
        • Honda T.
        • Tokura Y.
        Acquired idiopathic generalized anhidrosis (AIGA) and its complications: implications for AIGA as an autoimmune disease.
        Int. J. Mol. Sci. 2021; 22: 8389
        • Low P.A.
        • Caskey P.E.
        • Tuck R.R.
        • Fealey R.D.
        • Dyck P.J.
        Quantitative sudomotor axon reflex test in normal and neuropathic subjects.
        Ann. Neurol. 1983; 14: 573-580
        • Sano K.
        • Asahina M.
        • Uehara T.
        • Matsumoto K.
        • Araki N.
        • Okuyama R.
        Degranulation and shrinkage of dark cells in eccrine glands and elevated serum carcinoembryonic antigen in patients with acquired idiopathic generalized anhidrosis.
        J. Eur. Acad. Dermatol. Venereol. 2017; 31: 2097-2103
        • Sawada Y.
        • Nakamura M.
        • Bito T.
        • Fukamachi S.
        • Kabashima R.
        • Sugita K.
        • et al.
        Cholinergic urticaria: studies on the muscarinic cholinergic receptor M3 in anhidrotic and hypohidrotic skin.
        J. Invest. Dermatol. 2010; 130: 2683-2686
        • Fukunaga A.
        • Horikawa T.
        • Sato M.
        • Nishigori C.
        Acquired idiopathic generalized anhidrosis: possible pathogenic role of mast cells.
        Br. J. Dermatol. 2009; 160: 1337-1340
        • Takahagi S.
        • Okamoto M.
        • Ishii K.
        • Tanaka A.
        • Mizuno H.
        • Harada N.
        • et al.
        Clinical and histological characterization of transient dermal pain triggered by sweating stimuli.
        Allergol. Int. 2022; 71: 362-372
        • Sano K.
        • Asahina M.
        • Araki N.
        • Iwaya M.
        • Uehara T.
        GCDFP15 leakage associated with inflammation and eccrine gland atrophy in acquired idiopathic generalized anhidrosis.
        Jpn. J. Perspir. Res. 2022; 29: 2-8
        • Kaciuba-Uscilko H.
        • Grucza R.
        Gender differences in thermoregulation.
        Curr. Opin. Clin. Nutr. Metab. Care. 2001; 4: 533-536
        • Yehuda S.
        • Kastin A.J.
        Peptide and thermoregulation.
        Neurosci. Biobehav. Rev. 1980; 4: 459-471
        • Evans S.S.
        • Repasky E.A.
        • Fisher D.T.
        Fever and the thermal regulation of immunity: the immune system feels the heat.
        Nat. Rev. Immunol. 2015; 15: 335-349
        • Foley J.W.
        • Zhu C.
        • Jolivet P.
        • et al.
        Gene expression profiling of single cells from archival tissue with laser-capture microdissection and Smart-3SEQ.
        Genome Res. 2019; 29: 1816-1825