Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that predominantly affects areas with apocrine sweat glands. It is characterized by painful nodules, abscesses, and fistulas, occurring in the axillae, groin, buttocks, and under the breasts. The estimated global prevalence ranges from 0.00033% to 4.1%, with reports of 0.7% to 1.2% in Europe and the United States.
Although HS is a skin disease, systemic inflammation can also affect the eyes. Approximately 13.89% of HS patients have some ocular findings. The most common ocular complication is uveitis, followed by scleritis and keratitis. Another study reported that episcleritis showed the strongest association.
The pathogenesis of HS primarily involves occlusion of the pilosebaceous unit 2). Subsequent follicular rupture and immune response trigger an inflammatory cascade, leading to systemic elevation of inflammatory cytokines such as TNF, IL-1, IL-17, and IL-23 2). These cytokines are also deeply involved in the pathogenesis of uveitis and dry eye 1), and are considered to partly explain the mechanism of ocular complications in HS.
HS shares some immunological mechanisms with spondyloarthritis-related immune diseases such as psoriasis, Crohn’s disease, and ulcerative colitis, as well as vasculitides such as Behçet’s syndrome and systemic lupus erythematosus. Ocular complications are well known in these diseases, and a similar risk exists in HS.
Because hidradenitis suppurativa (HS) involves systemic inflammation, ocular complications can occur. Even without symptoms, regular ophthalmologic screening is recommended. If symptoms such as redness, pain, blurred vision, or photophobia appear, please see an ophthalmologist promptly. Collaboration between dermatologists and ophthalmologists is important.
The following ocular symptoms associated with HS have been reported:
The severity of symptoms varies based on flares (relapses) due to environmental factors, stress, and comorbidities.
Inflammatory Lesions
Anterior uveitis: One of the most common ocular complications. Presents with ciliary injection and inflammatory cells in the anterior chamber.
Posterior uveitis: May be accompanied by vitreous opacities and retinal vasculitis.
Scleritis/episcleritis: Inflammatory congestion of the sclera. Some reports indicate that episcleritis shows the strongest association.
Interstitial keratitis: Inflammation of the corneal stroma. Severe cases can lead to vision loss.
Ocular surface and retinal findings
Blepharokeratoconjunctivitis: Cases presenting with bilateral corneal neovascularization and inferior corneal thinning have been reported.
Meibomian gland dysfunction: Can cause dry eye due to gland dysfunction.
Retinal vascular changes: On OCTA, decreased foveal VD and VLD, as well as decreased VD in the deep retinal capillary plexus, have been reported.
Periorbital lesions: Rarely, HS lesions may appear on the face and eyelids.
Studies using OCTA have detected retinal microvascular abnormalities even in HS patients without clinical eye disease. These findings are similar to those seen in diabetic retinopathy and are thought to reflect the comorbid risk of HS and type 2 diabetes.
Approximately 13.89% of HS patients are reported to have ocular findings. Uveitis is the most common, followed by scleritis/episcleritis and keratitis. However, since studies on these ocular complications included patients with other autoimmune diseases, the exact frequency in HS alone has not yet been established.
The primary defect in the pathogenesis of HS is follicular occlusion of the pilosebaceous unit 2). Histologically, early findings include infundibular acanthosis, hyperkeratosis, and perifollicular immune cell infiltration 2). The immune response following follicular rupture triggers an inflammatory cascade, leading to the formation of nodules, abscesses, and fistulas.
In the study by Fitzsimmons and Gilbert, HS aggregation was observed in 14 out of 23 families, and 30% of patients had a strong family history. Abnormalities in the Notch signaling pathway are involved, and mutations in the PSENEN, KRT5, POFUT1, and POGLUT1 genes have been reported 3). Since the Notch pathway is also involved in melanocyte homeostasis and hair follicle differentiation control, its abnormalities may affect not only the skin but also multiple organs 3).
TNF, IL-1, IL-17, and IL-23 are elevated in the skin and serum levels 2). Among these cytokines, TNF-α and IL-6 are deeply involved in the pathogenesis of uveitis and correlate with ocular pain in dry eye 1). Epithelial cells release TNF-α, IL-1, IL-6, and IL-8, amplifying the immune response and attracting inflammatory cells 1).
| Risk Factor | Impact |
|---|---|
| Smoking | Promotes epidermal hyperplasia and follicular occlusion |
| Obesity | Associated with severity |
| Medications (lithium, etc.) | Reported to induce HS |
Lithium can directly act on hair follicle keratinocytes and induce HS through neutrophil migration and phagocytosis promotion 4). Discontinuation of lithium improves skin symptoms 4).
HS is primarily diagnosed clinically, based on the following three criteria 2).
Severity is classified into three stages using the Hurley classification 2).
| Hurley Classification | Features |
|---|---|
| Stage I | Isolated abscess. No fistulas or scars. |
| Stage II | Recurrent abscess. Fistula formation present. |
| Stage III | Extensive interconnected fistulas and abscesses. |
The majority are Stage I (68%) or Stage II (28%), with Stage III accounting for only 4% 2).
Regardless of symptoms, the following ophthalmic examinations are recommended for HS patients.
Ocular symptoms of HS require differentiation from the following diseases.
Differentiation from Crohn’s disease is particularly important. HS and Crohn’s disease coexist in 17–40% of patients 2) and share similar immune dysregulation. Treatment response may also provide diagnostic clues. If ocular symptoms improve after systemic therapy targeting HS-specific cytokines, it supports the diagnosis.
Treatment of HS follows a stepwise approach based on severity.
Step 1 (Mild): Topical or oral antibiotics (doxycycline, clindamycin, etc.)
Step 2 (Moderate): Addition of oral or injectable steroids
Step 3 (Severe/Refractory): Introduction of biologic agents
Currently, two biologic agents are approved for HS:
In HS patients with ophthalmic comorbidities, it has been reported that they respond poorly to topical dermatological treatments but respond well to anti-TNF-α therapy. TNF-α is also involved in the early pathogenesis of uveitis 1), and anti-TNF-α therapy has the advantage of simultaneously treating both skin and eye symptoms of HS.
There is also evidence that biologic users have a lower risk of conjunctivitis compared to non-users.
Yes, anti-TNF-α therapy (adalimumab, infliximab) has been reported to be effective not only for skin symptoms but also for ocular inflammation. Since TNF-α is involved in the pathology of uveitis and dry eye, this treatment has the advantage of simultaneously treating both the skin and eyes of HS. In HS patients with ophthalmic comorbidities, topical skin treatment alone is often insufficient, and systemic anti-TNF-α therapy is often required.
The pathology of HS begins with occlusion of the pilosebaceous unit 2). Early histological changes include infundibular acanthosis and hyperkeratosis, followed by lymphohistiocytic immune cell infiltration around the hair follicle. Rupture of the hair follicle causes leakage of keratin into the surrounding tissue, triggering a strong inflammatory response 2).
In this inflammatory process, TNF, IL-1, IL-17, and IL-23 are elevated in the skin and serum. These elevated cytokines expand perifollicular inflammation, progressing from abscess and nodule formation to draining fistulas.
Many of the cytokines elevated in HS are also involved in the pathology of ocular inflammation. TNF-α induces the expression of chemokines and adhesion molecules, prolonging inflammation in uveitis 1). IL-6 is involved in intraocular immune responses in several types of uveitis and correlates with ocular pain in dry eye 1).
A review by Rojas-Carabali et al. showed that epithelial cells produce and release TNF-α, IL-1, IL-6, and IL-8, amplifying the immune response and promoting the attraction of inflammatory cells in dry eye 1).
Furthermore, IP-10/CXCL10 is a chemokine released from leukocytes, neutrophils, eosinophils, monocytes, and stromal cells in response to IFN-γ, and is also involved in intraocular inflammation 1).
HS and Crohn’s disease share significant increases in IL-1, IL-6, IL-17, IL-23, and TNF 2). Both diseases are histologically characterized by lymphoid follicles and granulomas, and coexist in 17–40% of patients 2). Ocular complications are well known in inflammatory bowel disease including Crohn’s disease, and HS is thought to similarly affect the eyes through systemic inflammatory dysregulation.
Abnormalities in the Notch signaling pathway have attracted attention as a genetic background of HS. Mutations in PSENEN, a subunit of the γ-secretase complex, inhibit intracellular cleavage of Notch receptors 3). Disruption of the Notch pathway causes abnormal proliferation and differentiation of hair follicles, leading to epidermal hyperkeratosis and follicular occlusion. This mechanism explains the coexistence of Dowling-Degos disease and HS 3).
Recent studies using OCTA have detected abnormalities in the retinal microvasculature even in HS patients without clinical eye disease. Decreases in foveal vessel density (VD) and vessel length density (VLD), as well as reduced VD in the deep retinal capillary plexus, have been reported, suggesting that HS may cause potential retinal vascular complications.
Anti-TNF-α therapy has shown efficacy for both skin and ocular symptoms of HS and is expected to continue playing a central role in treatment. As new biologic agents and JAK inhibitors are developed, verification of their effectiveness against HS ocular complications is anticipated.
The exact prevalence and pathogenesis of ocular complications in HS patients are not yet fully understood. Large-scale prospective studies are needed to identify the frequency and risk factors of HS-specific ocular symptoms and to establish optimal screening protocols.
