Researchers at Wakayama Medical University conducted a retrospective single-center study of 26 patients with PCM treated between March 2016 and April 2025. The team, led by Kyoko Muraoka and colleagues in the Department of Dermatology, divided patients into two groups according to their antinuclear antibody, or ANA, status and compared baseline characteristics, allergic background, laboratory investigations, extent of skin involvement, and responsiveness to topical corticosteroids. Their findings, published in the Journal of Cutaneous Immunology and Allergy, offer the first systematic look at ANA positivity in PCM and hint that the disease may not be immunologically uniform after all.

PCM was long considered a predominantly type 2 inflammatory disorder, driven by the same Th2-skewed immune axis that underlies atopic dermatitis and chronic spontaneous urticaria. Many patients exhibit elevated serum total IgE levels, sensitization to specific allergens, and increased levels of thymus and activation-regulated chemokine, or TARC, which promotes eosinophil activation. Yet PCM is often highly refractory to topical corticosteroids and antihistamines, suggesting that its pathogenesis involves complex immunological and neurological interactions beyond a simple allergic response. Recent work has implicated mediators such as β-endorphin and autotaxin in directly or indirectly stimulating peripheral sensory nerve endings, contributing to the intractable pruritus that defines chronic prurigo including PCM. Age-related physiological skin changes, including impaired barrier function and immunosenescence, may further amplify these inflammatory processes in older adults.

The research team focused on ANA as a potential pathophysiological difference between PCM and related disorders. In atopic dermatitis, the ANA positivity rate has been reported at 31.3 percent, with positive patients exhibiting more severe facial eruptions and significantly lower leukocyte counts. A major target autoantigen in those cases, human elongation factor-1α, has been identified, and patients positive for antibodies against it demonstrate clinical features resembling systemic lupus erythematosus. In prurigo nodularis, by contrast, the ANA positivity rate was reported at 14.3 percent, and ANA-positive patients did not subsequently develop connective tissue diseases during follow-up. Against this backdrop, the Wakayama team set out to determine, for the first time, the prevalence and clinical significance of ANA positivity in PCM.

The results were striking. Five of the 26 patients, or 19.2 percent, tested positive for ANA by indirect immunofluorescence using HEp-2 cells, with positivity defined as a titer of 1:40 or greater. Two showed mixed homogeneous and speckled staining patterns at 1:40, one showed a homogeneous pattern at 1:40, one showed a speckled pattern at 1:40, and one showed a homogeneous pattern at 1:80. No patients had documented connective tissue diseases or other autoimmune conditions typically associated with ANA positivity, and none were considered paraneoplastic despite two patients having concomitant malignancies whose clinical course was unrelated to their skin disease.

When the researchers compared clinical and laboratory parameters between ANA-positive and ANA-negative groups, no significant differences emerged in age at onset, sex distribution, or disease duration. But two findings stood out. Among the 21 patients whose specific IgE levels were evaluated, the prevalence of sensitization to at least one allergen was dramatically higher in ANA-positive patients, reaching 100 percent compared with just 37.5 percent in ANA-negative patients, a difference that achieved statistical significance at p = 0.035. In contrast, the frequency of elevated total IgE levels did not differ meaningfully between the two groups, at 40.0 percent versus 33.3 percent.

The second key finding was a paradoxical hematological profile. The median peripheral blood eosinophil percentage was significantly lower in ANA-positive patients, at 4.0 percent, compared with 8.0 percent in ANA-negative patients, with p = 0.031. The median absolute eosinophil count was also numerically lower in the ANA-positive group, at 399.0 per microliter versus 798.0 per microliter, though this did not reach statistical significance. This inverse relationship between ANA status and eosinophilia is intriguing because strong allergic sensitization, as reflected by universal specific IgE positivity in all tested ANA-positive patients, would ordinarily be expected to accompany increased peripheral eosinophil counts as part of a typical Th2 inflammatory response.

The authors propose several possible explanations for this discordance. Recent studies have demonstrated that different biomarkers of Th2 inflammation may indicate distinct immunological axes, with eosinophils primarily reflecting IL-5-related inflammation and IgE more closely reflecting IL-4 and IL-13-related inflammation. Therefore, discordance between eosinophils and IgE may occur even within Th2-dominant inflammation. Alternatively, the reduced eosinophil percentage may reflect not depletion of eosinophils themselves but rather enhanced recruitment of circulating eosinophils into lesional skin tissue, the primary site of inflammation. Serum TARC levels were elevated in a high proportion of PCM patients overall, at 73.9 percent, suggesting active migration of Th2 cells and eosinophils into the dermis. In ANA-positive patients, certain immunological triggers may induce eosinophil recruitment to the skin at a level exceeding the circulating pool, thereby relatively reducing peripheral blood eosinophil percentages. The marked eosinophilic infiltration observed in perivascular and intercollagenous spaces in a representative histopathological specimen from an ANA-positive patient further supports this hypothesis.

Perhaps most compelling is the parallel the authors draw with chronic spontaneous urticaria, another type 2 inflammatory disorder known to involve both type I autoallergy, mediated by IgE autoantibodies against self-antigens, and type IIb autoimmunity, mediated by IgG autoantibodies against FcεRI or IgE. Patients with type IIb autoimmunity are clinically characterized by ANA positivity, low eosinophil and basophil counts, and treatment resistance. Although total IgE levels are often low in typical type IIb cases, overlap phenotypes between type I and type IIb autoimmunity have been reported, and these patients do not necessarily exhibit low total IgE levels. A similar overlap-type immune dysregulation may underlie ANA-positive PCM cases, suggesting that the condition may encompass multiple endotypes rather than a single homogeneous inflammatory process.

Treatment outcomes were uniformly poor across both subgroups, with all five ANA-positive patients and 16 of 21 ANA-negative patients showing poor response to topical corticosteroids. The median body surface area affected was 22.0 percent in ANA-positive patients versus 12.0 percent in ANA-negative patients, a difference that was not statistically significant. The authors acknowledge several limitations, including the single-center design, relatively small sample size, retrospective methodology, and lack of direct correlation between peripheral blood eosinophil counts and actual eosinophilic infiltration in skin lesions. They also note that ANA positivity is known to increase with aging, and some cases may simply reflect nonspecific age-related autoantibodies, though the distinct immunological characteristics observed suggest these findings cannot be explained solely by age-related changes. Larger multicenter studies incorporating quantitative histopathological and immunological analyses will be needed to validate these findings and investigate the interplay between autoimmunity and allergic inflammation in PCM, a disorder that demands both high diagnostic accuracy and flexible therapeutic strategies in dermatological practice.

Subject of Research: Antinuclear antibody positivity rate and clinical characteristics in prurigo chronica multiformis: a retrospective study of 26 patients

Article Title: Antinuclear antibody positivity rate and clinical characteristics in prurigo chronica multiformis: a retrospective study of 26 patients

Article References: Muraoka, K., Inaba, Y., Kayama, K., & Jinnin, M. (2026). Antinuclear antibody positivity rate and clinical characteristics in prurigo chronica multiformis: a retrospective study of 26 patients. Journal of Cutaneous Immunology and Allergy, 9, Article 17229. https://doi.org/10.3389/jcia.2026.17229

Image Credits: AI Generated

DOI: 10.3389/jcia.2026.17229

Keywords: prurigo chronica multiformis, antinuclear antibody, chronic prurigo, eosinophil, IgE, autoimmunity, type 2 inflammation, dermatology, Antinuclear, antibody, positivity, rate