Sjögren’s disease (SjD) typically presents with three initial symptoms: dry mouth and eyes, fatigue, and joint pain. These three symptoms (dryness, fatigue, and pain) are observed in over 80% of (SjD) patients. Approximately 55% exhibit autonomic nervous system symptoms, and decreased sweating function has been reported as a statistically significant finding compared to healthy controls [1], but generalized anhidrosis as an initial symptom is extremely rare. Here, we report a case of SjD diagnosed following the presentation of generalized anhidrosis.

A 50-year-old Japanese woman presented to our department with the chief complaint of decreased sweating throughout her body. She had a history of a pituitary tumor. Ten years prior, she had noticed decreased sweating but had not sought medical attention. During summer, she experienced heat retention even in air-conditioned rooms and managed this with cold compresses. At her initial dermatological visit, there were no skin rashes and she reported no episodes suggestive of cholinergic urticaria. On further questioning, she reported a prior history of oral and conjunctival dryness and numerous treated dental caries. Minor’s test revealed anhidrosis covering 98% of her body surface area (Figure 1).

Blood tests showed that carcinoembryonic antigen (CEA), thyroid function, and blood glucose were within normal ranges, and hepatitis B and C serologies were negative, ruling out hypothyroidism, diabetes, and active infection. CEA levels are elevated in acquired idiopathic generalized anhidrosis (AIGA) [2], but no such elevation was observed. Antinuclear antibody and anti-SS-A/Ro antibody were positive, raising suspicion of SjD, and the patient was referred to a rheumatologist. Subsequent tests confirmed reduced glandular function: Saxon test: 0.636 g (normal value ≥2 g/2 min), gum test: 3.98 mL (normal value ≥10 mL/10 min), Schirmer’s test: 3 mm in the right eye and 2 mm in the left eye (normal value ≥5 mm/5 min). Imaging studies revealed decreased uptake in the submandibular and parotid glands and fatty infiltration of both parotid glands on salivary gland scintigraphy. Histological examination showed lymphocyte and plasma cell infiltration around the salivary gland ducts. Histopathological examination of the anhidrotic area using Minor’s test revealed hydropic degeneration of the sweat glands. Based on these findings, the patient was diagnosed with generalized anhidrosis and SjD. After a 3-day course of intravenous methylprednisolone (500 mg/day), oral prednisolone 25 mg/day was initiated and gradually tapered. One year later, the patient noticed slight sweating in her hands and head. The patient is satisfied with the treatment for Sjögren’s disease and the management of heat retention. Table 1 provides a timeline of the events.

AIGA is a rare condition characterized by anhidrosis affecting more than 25% of the body surface area without other neurological abnormalities or sweat gland pathology; approximately 90% of cases occur in young men, and it is most common among Asian men [3, 4]. In this case, the AIGA diagnostic criteria were met. However, in diagnosing anhidrosis, the most important challenge is differentiating AIGA from secondary anhidrosis. To confirm the diagnosis, secondary causes, particularly autoimmune diseases, drug-induced causes, endocrine/metabolic disorders, and neurodegenerative diseases, must be ruled out. In this case, AIGA was initially suspected, but a detailed medical history and physical examination revealed a history of dental caries and dry eye, leading to an early diagnosis of SjD.

It has been reported that anhidrosis caused by SjD arises through two primary mechanisms: direct autoimmune inflammation of the sweat glands [5] and autonomic dysfunction [6]. In anhidrosis resulting from direct sweat gland damage, lymphocytic autoimmune hidradenitis plays a central role. Pathological examination reveals dense lymphocytic and plasma cell infiltration around the secretory portions of eccrine sweat glands, accompanied by glandular atrophy [7]. In anhidrosis caused by autonomic dysfunction, dysfunction of the postganglionic sympathetic cholinergic system is observed, and abnormal reduced sweating along dermatomes may be detected using the Quantitative Sweat Axon Reflex Test [6]. Histopathological examination in this case revealed hydropic degeneration of the sweat glands on hematoxylin and eosin staining, without glandular atrophy or marked inflammatory cell infiltration.

Sweat glands are composed of clear cells, dark cells, and myoepithelial cells [8]. In normal sweat glands, the secretory coil exhibits a bilayered architecture, with dark cells located in the inner layer and clear cells arranged in the outer layer. In this study, sweat glands were evaluated using carbonic anhydrase II (CAII), a marker of clear cells, and GCDFP15, a marker of dark cells [9]. Sano et al. reported that hydropic degeneration of clear cells, followed by cellular breakdown, frequently occurs in the anhidrotic skin of patients with AIGA, ultimately resulting in collapse of the bilayer architecture and glandular atrophy [10]. In the present case, the sweat glands showed hydropic degeneration without overt atrophy or accompanying inflammatory cell infiltration. This hydropic degeneration was associated with disruption of the bilayer structure, characterized by aberrant CAII expression in clear cells and sparse, markedly reduced GCDFP15 expression in dark cells (Figures 2, 3). Unlike previously reported pathological features of anhidrosis in SjD, the absence of infiltration of inflammatory cells and absence of sweat gland atrophy was an atypical pathological appearance. However the absence of inflammatory cell infiltration suggests that any preceding inflammatory process may have subsided during the 10-year disease course. It is also conceivable that inflammatory cytokines released by infiltrating immune cells caused irreversible damage to the sweat glands and adjacent autonomic nerve fibers, thereby contributing to the development of anhidrosis.

No standard treatment has been established for SjD-associated anhidrosis [11]. In contrast, pulse corticosteroid therapy has been reported to be effective in AIGA, with an overall response rate of approximately 73%, and early intervention is considered particularly important [10].

Hydropic degeneration likely represents an edematous change predominantly affecting clear cells and may reflect a milder, potentially reversible stage of sweat gland injury compared with glandular destruction or atrophy. Recovery of sweating function may therefore still be possible if appropriate treatment is initiated before irreversible structural damage develops. This distinctive pathological change can be observed in AIGA. Moreover, the absence of inflammatory cell infiltration closely resembles the pathological features of non-inflammatory AIGA [9], in which the initial ductal inflammation may have subsided, leaving residual glandular abnormalities including hydropic degeneration and acinar atrophy. From a pathological perspective, the possibility that SjD was superimposed on pre-existing AIGA cannot be entirely excluded. Nevertheless, the patient was a woman in her 50s, lacked features characteristic of AIGA such as elevated serum CEA levels and cholinergic urticaria, showed no response to a half-pulse steroid therapy. Based on clinical progress, it cannot be ruled out that SjD was coexisting with AIGA, but it was diagnosed as SjD associated with generalized anhidrosis.

This case is a valuable example of SjD presenting with the atypical initial symptom of generalized anhidrosis. In patients with anhidrosis, especially those suspected of having AIGA, a detailed medical history and systematic evaluation are essential to avoid overlooking underlying autoimmune diseases and to facilitate early therapeutic intervention.