Abstract
Introduction
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with systemic inflammation and high impact on quality of life. Treatment strategies are still inadequate with a lack of inflammation biomarkers. We conducted a prospective study to assess the correlation between serum amyloid A (SAA) levels and active lesion count; disease severity; Dermatology Life Quality Index (DLQI); smoking; BMI; and lesion sites.
Methods
Forty-one patients (M/F: 22/19) were enrolled. Demographic, clinical, laboratory, and therapeutic data were assessed at baseline on patients not under treatment or in wash-out from systemic treatment for at least 2 weeks. Associations were investigated by univariate and multivariate analyses.
Results
SAA levels were significantly associated with number of nodules (p = 0.005), abscesses (p < 0.001), fistulas (p = 0.016), and severe IHS4 (p = 0.088 and r = 0.514). Gluteal localization was correlated with high values of mSartorius and severe IHS4.
Conclusions
We recommend assessment of SAA levels to monitor therapeutic response in patient with HS in order to prevent disease's flare and potential complications.
Keywords: Acne inversa, Hidradenitis suppurativa, Inflammatory skin disease, Serum amyloid A, Inflammation, Biomarker
Introduction
Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease, characterized by recurrent and painful nodules, abscesses, and sinus tracts involving the hair follicle of intertriginous areas, with systemic inflammation [1]. Despite the high impact on quality of life and the development of psychiatric comorbidities, treatment strategies are still limited and inadequate with poor understanding of the cytokine network underlying inflammation [2].
One of the most highly expressed cytokines is IL-1β, which correlates with blood levels of serum amyloid A (SAA), making it an important biomarker of inflammation [3]. A biomarker is defined as “a characteristic that is measured as an indicator of normal biological, pathogenic processes, or responses to an exposure or intervention” [4]. There are diagnostic biomarkers that help in the differential diagnosis between HS and other inflammatory conditions such as acne, folliculitis, or infection; monitoring biomarkers that correlate with disease severity and predictive biomarkers of treatment response. In a recent systematic literature review of 106 articles, only 1 diagnostic marker (serum IL-2R), 1 monitoring (dermal Doppler vascularity), and 2 predictive biomarkers (epithelialized tunnels and positive family history of HS) reached a high degree of evidence emphasizing the need for more research on this topic [5].
High levels of inflammation with elevated SAA are associated with an increased risk of complications such as soft tissue infections up to sepsis, extensive shrinking scars with functional limitation, anemia, hypoproteinemia, nephrotic syndrome, arthropathy, and systemic amyloidosis [6]. Blood levels of SAA, C-reactive protein levels, and erythrocyte sedimentation rate were significantly associated with Hurley staging, Sartorius score, and nodule count in patients with HS [3, 7]. Based on this literature evidence, we conducted a prospective study to assess the correlation between SAA levels and disease severity, BMI, smoking status, Dermatology Life Quality Index (DLQI), and lesion sites.
Methods
This prospective study was performed in accordance with the Declaration of Helsinki for research on human subjects. Primary endpoint was to assess the correlation between disease severity, in terms of mSartorius, Hidradenitis Suppurativa Physician Global Assessment (HS-PGA), International Hidradenitis Suppurativa Score (IHS4), and SAA levels. Secondary endpoint was to investigate the correlation between BMI, smoking status, DLQI, and SAA levels and the correlation between lesion sites and disease severity.
We recruited adult patients diagnosed with HS referred to our clinic from April 2018 to December 2021. Individual patient data were collected in access databases with the following structure: patient initials, sex, age, smoke habit, DLQI, mSartorius, HS-PGA, IHS4, SAA level, and sites involved. Data were obtained at baseline on patients not under treatment or in wash-out from systemic treatment for at least 2 weeks. SAA level was measured at hospital central laboratory. Data collected were then entered into a single Excel file and subjected to statistical analysis. Categorical data were described by absolute and relative frequency, continuous data by mean and standard deviation. To compare SAA levels, BMI, smoke, and sites involved with continuous clinical factors (DLQI, mSartorius, HS-PGA, and IHS4), Pearson's correlation analyses were performed followed by multiple linear regression as multivariate analysis, in order to minimize possible confounding factors. The IHS4 score was further stratified into mild (<3 points), moderate (4–10 points), and severe (>11 points). Significance was fixed at 0.05, and all analyses were carried out with SPSS v.28 technology.
Results
We included in the study 41 patients. Table1 reports the characteristics of population. The average SAA value in our patients was found to be 69.92 μg/mL (range 1.3–952 μg/mL).
Table 1.
Characteristics of the population
| Characteristics | Statistics |
|---|---|
| Age | 39.0 (15.5) |
| BMI | 28.8 (6.1) |
| DLQI | 11.1 (7.9) |
| m_Sartorius | 36.3 (28.9) |
| HS_PGA_num | 3.1 (1.0) |
| IHS4_num | 14.2 (15.9) |
| N_inflammatory_nodules | 2.5 (2.8) |
| N_Abscess | 2.7 (2.6) |
| N_draining_fistulas | 1.6 (2.9) |
| Smoking | |
| No | 13 (32.5) |
| Yes | 27 (67.5) |
| Comorbidities | |
| No | 17 (42.5) |
| Yes | 23 (57.5) |
| Inguinal involvement | |
| No | 16 (40.0) |
| Yes | 24 (60.0) |
| Axillary involvement | |
| No | 17 (42.5) |
| Yes | 23 (57.5) |
| Genital involvement | |
| No | 35 (87.5) |
| Yes | 5 (12.5) |
| Gluteal involvement | |
| No | 30 (75.0) |
| Yes | 10 (25.0) |
| Pubic involvement | |
| No | 30 (75.0) |
| Yes | 10 (25.0) |
| Breast involvement | |
| No | 32 (80.0) |
| Yes | 8 (20.0) |
| Perianal involvement | |
| No | 33 (82.5) |
| Yes | 7 (17.5) |
Statistics: mean (SD) or frequency (%).
Univariate analysis showed a statistically significant correlation between SAA levels and the number of nodules (p = 0.005), abscesses (p < 0.001), and fistulas (p = 0.016). No statistically significant correlation was found between SAA and BMI, smoking, and DLQI.
Multivariate analysis of the factors influencing SAA levels is shown in Table 2. We observed a statistically significant correlation between SAA levels and severe IHS4 (p = 0.088 and r = 0.514). Gluteal localization was correlated with high values of mSartorius and severe IHS4, confirming the greater severity of disease in patients with gluteal localization (Fig. 1).
Table 2.
Univariate and multivariate analysis of the factors influencing SAA
| Factor | Univariate analysis |
Multivariate analysis |
||
|---|---|---|---|---|
| r | p value | partial r | p value | |
| mSartorius | 0.430 | 0.006 | −0.192 | 0.533 |
| HS-PGA | 0.453 | 0.003 | 0.259 | 0.174 |
| IHS4 | 0.508 | <0.001 | 0.514 | 0.088 |
Statistics: r (Pearson's correlation coefficient).
Fig. 1.
Correlation between gluteal localization and mSartorius/IHS4.
Discussion
HS should be managed as a chronic inflammatory systemic disease. In the presence of persistent chronic inflammation, the liver produces an acute-phase protein called SAA whose proteolytic fragments can aggregate and precipitate damage to internal organs. It is reasonable to expect high SAA levels in patients with HS with the development of complications such as systemic amyloid A amyloidosis [8].
Literature data correlating SAA levels with HS severity are extremely limited. Although there are case reports correlating amyloid A amyloidosis to HS, individual patients' SAA values are not reported [1].
A study by a German team published in 2019 on 21 patients with HS identified a positive correlation with SAA, the Sartorius score, and more specifically the number of involved skin regions containing nodules, indicating SAA as an easy-to-monitor serum biomarker of inflammation [3]. Another study by a Turkish team found higher SAA levels (median range 2.67 μg/mL) in 44 HS patients compared to controls (median range 0.68 μg/mL) finding a weakly positive correlation of SAA levels with Hurley staging and recommending assessment of SAA levels as biomarker of disease severity [5].
Our results are in line with literature data and confirm the correlation between inflammatory lesion count, IHS4, and SAA levels, highlighting the important role of SAA as a monitoring biomarker of inflammation. The absence of significant correlations with the other dynamic disease scores (mSartorius and HS-PGA) could be explained by intrinsic characteristics of the scores: the IHS4 is based exclusively on the inflammatory lesion count, while the other scores are more complex and have more confounding calculation factors.
A single case report shows SAA levels before and after systemic antibiotic combination therapy treatment clindamycin plus rifampicin showing a reduction in SAA levels from 168 μg/mL to 8 μg/mL after 12 weeks [1]. Further studies are needed to clarify whether an effective therapeutic control of inflammation levels could prevent evolution of HS disease and complications and whether SAA levels may be a subclinical index of inflammation.
The limitations of the study are the monocentricity and the small sample that restrict the generalization of data. The strengths include the prospective design and the inclusion of patients not on systemic treatment or in wash-out.
Conclusions
Our findings confirm that SAA levels are an important monitoring biomarker of inflammation and reflect the active lesion count of patients by correlating with disease severity expressed in terms of IHS4. We recommend monitoring SAA levels in daily clinical practice in order to manage treatment and to prevent complications. Further researches are needed to confirm the role of SAA levels in HS in terms of pathogenetic role, potential prognostic value, clinical and therapeutic significance in order to improve management of patients with moderate-to-severe HS.
Statement of Ethics
This study protocol was reviewed and approved by Regional Ethics Committee for Clinical Trials of Tuscany, approval number 90411. Written informed consent was obtained from patients to participate in the study.
Conflict of Interest Statement
The authors have no conflict of interest to declare.
Funding Sources
The research reported in this article has not received external funding. No competing financial interests exist.
Author Contributions
Michela Iannone, Giorgia Salvia, Agata Janowska, Cristian Fidanzi, Matteo Bevilacqua, and Riccardo Morganti contributed to the conception and design, acquisition of data, and analysis and interpretation of data. Valentina Dini and Marco Romanelli were involved in drafting the manuscript and revising it critically for important intellectual content.
Data Availability Statement
All data generated or analyzed during this study are included in this article. Further requests may be directed to the corresponding author.
Funding Statement
The research reported in this article has not received external funding. No competing financial interests exist.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data generated or analyzed during this study are included in this article. Further requests may be directed to the corresponding author.