Hidradenitis suppurativa (HS) is a chronic inflammatory dermatosis that may lead to systemic complications, including secondary AA amyloidosis, a rare but potentially life-threatening condition 1, 2. We report seven cases of HS-associated AA amyloidosis collected from four Spanish centers through the CLINI-AEDV registry, along with practical screening recommendations. In our series (Table 1), five of the seven patients were male, median age at diagnosis of 54 years (range 28–67). All had severe, long-standing HS (Hurley stage III), with a median latency of 19 years (range 7–25) between disease onset and amyloidosis diagnosis. All were active smokers and exhibited the inflammatory phenotype. Secondary AA amyloidosis was confirmed by biopsy in all cases. The most frequent sites were kidney and subcutaneous tissue (5/7 each), followed by gastrointestinal tract (3/7, assessed via colonoscopy) and skin (1/7). Renal involvement was observed in all patients (proteinuria in each, nephrotic in six). Five patients progressed to renal insufficiency, three required hemodialysis, and one died from kidney-related complications. Other, less accessible organs were presumed involved based on imaging, clinical symptoms, and examination. Our cases align with the recent systematic review by Aw et al. 3, which described a predominance of middle-aged males (median age 48.2 ± 13.5 years), long disease duration (median 19.1 ± 13.8 years), and a high proportion of severe cases (83% Hurley III). This reinforces the concept that chronic, uncontrolled systemic inflammation is a central driver of sustained serum amyloid A (SAA) elevation, ultimately promoting AA deposition 1. Renal involvement confirms the kidney as the principal target organ 2. Only one case was detected through asymptomatic proteinuria, highlighting the challenge of early diagnosis and need for proactive surveillance. End-stage renal disease in our cohort (28.6%) exceeded that reported in the systematic review (15%), reflecting delayed recognition and potentially insufficient renal monitoring. A higher frequency of immunomodulated comorbidities was observed in our series (71% vs. 7%), including psoriasis, chronic inflammatory arthritis, and Crohn's disease. Two patients carried pathogenic mutations in genes associated with autoinflammatory syndromes (NLRC4 and MEFV), and two familial Mediterranean fever cases in the review suggest genetic predisposition may amplify systemic inflammation and accelerate amyloidogenesis. Advanced therapies may improve systemic inflammation control in HS, potentially reducing secondary AA amyloidosis risk. For example, in rheumatoid arthritis, AA amyloidosis affected 16.7%–25.2% of patients before 2010 but declined to 0.7% in the era of biologic therapies, illustrating the substantial impact of strict inflammation control 4. From a practical perspective, systematic, low-cost screening is essential. Simple tests, such as urine dipstick proteinuria or a single urine sediment examination, can facilitate early identification of secondary amyloidosis in high-risk patients 5. Persistently elevated inflammatory markers such as C-reactive protein remain the most relevant risk factor, though such data are often unavailable due to a lack of consensus on routine monitoring in HS follow-up. In their absence, additional clinical criteria are necessary. We recommend annual screening in high-risk patients: those with inflammatory or mixed phenotype, severe HS (Hurley stage III or IHS4 ≥ 10), and long-standing disease (≥ 10 years). Immune-mediated comorbidities or active smoking should be considered as additional indicators of inflammatory burden. If dipstick or sediment examination is positive, a 24-h urine protein measurement should be performed to confirm renal involvement. The proposed screening criteria, summarized in Table 2, are based on expert opinion and literature review and are pending validation in larger prospective cohorts. Additional risk factors: immune-mediated comorbidities or active smoking. In conclusion, secondary AA amyloidosis is a serious but potentially preventable complication of long-standing HS. Identifying high-risk patients is crucial, as simple, inexpensive screening methods can enable early detection, prevent renal progression, and ultimately improve prognosis. The authors have nothing to report. Alejandro Molina-Leyva declares consultancy/speaker's honoraria and/or travel grants and/or participated in clinical trials sponsored by AbbVie, Almirall, Boehringer Ingelheim, Celgene, Janssen Cilag, LEO Pharma, Lilly, Novartis, Pfizer, Sandoz, Sanofi, and UCB. Patricia Garbayo-Salmons declares honoraria for participating in advisory boards from Novartis; has received speaker's honoraria and/or travel support for attending meetings sponsored by Abbie, Amgen, Lilly, LEO Pharma, Novartis, and UCB. The other authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Lara-Moya et al. (Fri,) studied this question.