Pruritus is a common symptom of several skin diseases, both inflammatory and neoplastic. Pruritus might have a tremendous impact on patients’ quality of life and strongly interfere with sleep, social, and work activities. We review the role of type-2 inflammation and immunity in the pathogenesis of chronic pruritic conditions of the skin. Type 2 cytokines, including IL-4, IL-13, thymic stromal lymphopoietin, periostin, IL-31, IL-25, and IL-33 are released by mast cells, innate lymphoid cells 2, keratinocytes, and type 2 T lymphocytes, and are master regulators of chronic itch. These cytokines might act as direct pruritogen on primary sensory neurons (pruriceptors) or alter the sensitivity to other itch mediators Type 2 inflammation- and immunity-dominated skin diseases, including atopic dermatitis, prurigo nodularis, bullous pemphigoid, scabies, parasitic diseases, urticaria, and Sézary syndrome are indeed conditions associated with most severe pruritus. In contrast, in other skin diseases, such as scleroderma, lupus erythematosus, hidradenitis suppurativa, and acne, type 2 inflammation is less represented, and pruritus is milder or variable. Th2 inflammation and immunity evolved to protect against parasites, and thus, the scratching response evoked by pruritus might have developed to alert about the presence and to remove parasites from the skin surface.

Background: Pain is a core symptom of hidradenitis suppurativa (HS) and is of complex, multifactorial origin. HS patients frequently report typical neuropathic pain qualities, but its prevalence has been poorly described. Methods: In this cross-sectional study, we examine the prevalence of neuropathic pain (NP) component and related pain-characteristics of a hospital-based cohort of patients with symptomatic HS. We administered the pain-DETECT tool (PDQ), a validated screening tool for NP, collecting clinical and patient-reported data on pain, pruritus and pain-management. We obtained 110 complete datasets from symptomatic HS patients (49.1% females; Hurley I (27.3%])–II (45.5%)–III (27.3%)). According to the PDQ tool, 30% of patients were classified with a high probability (>90%) of neuropathic pain (LNP). LNP status was significantly associated with increased pain severity, disease activity, pruritus intensity and use of pain medication. Regression analysis showed a significant impact of the PDQ score on patient-reported outcomes, including pain severity and the dimensions of activity and affective pain interference. HS patients may present a mixed chronic pain phenotype with a neuropathic component, thus requiring additional pain-assessments. A multi-modal approach to pain management, in combination with disease-specific treatment, should be implemented in future interventional studies.

Introduction: Hidradenitis suppurativa is a complex, chronic, difficult to treat condition belonging to the spectrum of cutaneous immune-mediated inflammatory diseases. Systemic treatment options for moderate-severe disease are limited to TNF-alpha antagonists and other biologic agents, with limited clinical evidence. Patient concerns: We report two adult patients with severe hidradenitis suppurativa presenting concomitant psoriatic arthritis and multiple medical comorbidities. Both were ineligible or resistant to adalimumab, the only biologic drug approved for the treatment of hidradenitis. Diagnosis: Both patients were diagnosed with severe Hurley III-stage disease and psoriatic arthritis, showing resistance to first-line systemic treatments and a complex comorbidity profile. Interventions: Patients underwent treatment with apremilast, an oral phosphodiesterase-4 inhibitor, approved for the treatment of psoriatic arthritis. Outcomes: After 16 weeks of treatment, a clinically relevant improvement of inflammatory lesions, skin- and arthritis-related pain, and patient-reported outcomes was achieved in both patients. Apremilast was well tolerated and continued up to 48 weeks of treatment. Conclusion: We report the “real-life” use of apremilast in the treatment of multimorbid patients with hidradenitis suppurativa and review its potential role in the management of this severe condition.

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Adalimumab is the only biologic agent approved for the treatment of moderate-to-severe hidradenitis suppurativa (HS) patients (i.e., with Hurley II or III), which is recommended in two different maintenance doses (i.e., 40 mg weekly or 80 mg every two weeks). We conducted a prospective multicentric study to measure outcomes related to the severity of disease and quality of life (QoL) of patients affected by moderate-to-severe HS, treated with adalimumab at a maintenance dosing of 40 mg or 80 mg. Assessments were performed at baseline (T0) and after 32 weeks of treatment (T32). We enrolled 85 moderate-to-severe HS Italian patients, 43 men (50.6%) and 42 women, aged between 16 and 62 years (median 31 years, interquartile range 24.4–43.8). Statistically significant improvements were observed for clinical status (with a mean reduction of 7.1 points for the International Hidradenitis Suppurativa Severity Score System (IHS4)), pain levels (3.1 mean decrease in VAS), and QoL (3.4 mean improvement in DLQI score). Patients with no comorbidities, and those with higher levels of perceived pain showed significantly greater improvement in QoL than their counterpart from T0 to T32. As for the proportion of patients who at follow-up reached the minimal clinical important difference (MCID) in QoL, significantly higher proportions of success were observed for age (patients in the 29–39 category), pain (patients with higher reported pain), and Hurley stage III. While both treatment regimen groups (i.e., 40 vs. 80 mg) improved significantly, no statistical differences were observed when comparing the two treatment dosages.