Laboratory Studies
The following laboratory tests may be helpful in the evaluation of hidradenitis suppurativa (HS):
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CBC count with differential and platelet counts
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Assessment of erythrocyte sedimentation rate
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C-reactive protein assay
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Urinalysis
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Serum multiphasic analysis with determination of the serum iron level and serum protein electrophoresis
Patients with acute lesions may have an elevated erythrocyte sedimentation rate, elevated white blood cell count (occasionally), a low serum iron level, and serum protein abnormalities on electrophoresis.
Imaging Studies
Ultrasonography of the hair follicles and dermal thickness in hidradenitis suppurativa patients may reveal abnormalities in the deep part of the follicle. In the genitofemoral region, perilesional clinically normal hair follicles have an abnormal shape and are significantly wider in the deep part of the dermis, compared with control samples. Mean axillary and genitofemoral skin is significantly thicker in patients with hidradenitis suppurativa than in healthy control subjects. Thickened skin may play a role in the pathogenesis of hidradenitis suppurativa.
Other Tests
Bacteriologic analysis should include bacteriologic sampling and cultivation. Almost every microorganism known to bacteriologists can be isolated from hidradenitis suppurativa lesions; these microorganisms include streptococci, gram-positive and gram-negative rods, and the full range of fecal bacteria. [73] Among the most frequently found species are Staphylococcus aureus and coagulase-negative staphylococci, anaerobic streptococci (eg, microaerophilic Streptococcus milleri), and Bacteroides species. [30, 40]
The microbiologic florae are not consistent and change unpredictably. [73]
Immunohistochemical data obtained for various cytokeratins (CKs) and the 6 desmosomal cadherins (ie, desmogleins [Dsgs] 1-3, desmocollins [Dscs] 1-3) showed 3 phenotypes of stratified squamous epithelia covering the sinus tracts in hidradenitis suppurativa: type I cornifying, type II noncornifying and moderately inflamed, and type III noncornifying and strongly inflamed. [79]
The noncornifying types II and III epithelia are characterized by the absence of the terminal differentiation markers CK10 and Dsc1 and by the strong expression of Dsg2 in the basal layer. Compared with the normal epidermis and type I epithelium, types II and III epithelia have Dsc2 and Dsg3 in all layers, whereas Dsc3 is restricted to the basal and parabasal layers. The inflammatory character of type III epithelium, as opposed to that of types I and II, is marked by the presence of CK7 and CK19 and the absence of Dsg1. [79]
All 3 types of epithelia are clearly distinct from the interfollicular epidermis because of the absence of CK2e and the presence of CKs 6, 13, 15, and 16; the presence of these proteins reflects the fact that the sinus tract epithelia have undergone the pathologically altered process of growth, differentiation, and inflammation.
CK19 is commonly found in the basal cells of noncornifying stratified squamous epithelia, such as in the outer root sheath (ORS) of the hair follicle. The strongly inflamed CK19-positive parts of the sinus epithelium show no signs of terminal squamous differentiation (ie, nuclei were present in the highest suprabasal layers, and keratohyalin granules were absent). Instead, the inflamed CK–positive parts resembled epidermal keratinocytes grown in organotypic culture, which can be induced to build a noncornifying epithelium and to express CK19 with the addition of retinoic acid to the culture medium.
In all specimens in one study, type I epithelium near the opening of the sinus showed strong similarities to the upper pilosebaceous duct from which the inflammation process seemed to emerge.
In both normal pilosebaceous duct epithelium and cornifying type I sinus epithelium, CK5 and CK14 are restricted to the basal layer, CK10 and Dsc1 antibodies label the suprabasal cells, Dsg1 and Dsg3 are present in an epidermislike pattern, and CK2e is absent.
The relationship of the sinus epithelium to the hair follicles and the apocrine glands has long been debated. [32] The sinus epithelium is clearly distinct from the normal epithelium of the subinfundibular ORS of the hair follicle. Thus, CKs 5 and 14 and Dsg2 always remain restricted to the basal cell layer of the sinus epithelium, whereas in the subinfundibular ORS, they are also expressed in the suprabasal layer. The relationship of the sinus epithelium to hair follicles and apocrine glands is in agreement with the theory that hidradenitis suppurativa lesions are caused by follicular plugging and subsequent rupture of the follicular epithelia. The exact role of inflammation in such patterns of differentiation has yet to be elucidated.
Thus, in another study of the hidradenitis suppurativa cytokeratin expression reported by Kurokawa et al, the draining sinus tract epithelium of hidradenitis suppurativa lesions were divided into 3 components: infundibular-like keratinized epithelium (type-A), noninfundibular keratinized epithelium (type B), and nonkeratinized epithelium (type C). [80] Types A and B were similar to the types I and II reported by Kurzen et al, [79] although CK17 was not detected in type A, suggesting fragility of this epithelial type. CK17, which is normally present in the suprabasal layers of healthy skin, represents a useful marker for differentiation of epithelial cells. It is a spacial keratin and has a function related to the maintenance of the 3-dimensional cytoskeleton structure of human adnexal glands. Thus, the absence of CK17 may reflect a fragile follicular structure, resulting in rupture of the follicle, which subsequently forms a subcutaneous abscess. [81]
CK expression in pilonidal sinus is comparable with that in hidradenitis suppurativa, as previously reported. Moreover, in infundibularlike epithelium, CK17 is also absent. [81]
The overlying epidermis in hidradenitis suppurativa lesions has a more undifferentiated hyperproliferative state than that found in healthy epidermis. [80] In some cases, CK19 is present in the basal layer of the epidermis, and CK19 is thought to be associated with premalignant change. [82]
Histologic Findings
Histologically, the fundamental change in hidradenitis suppurativa is the same as in acne vulgaris, namely, hyperkeratosis of the infundibulum that results in comedolike horny impactions. [73] Some evidence suggests that the occlusion of abnormal hair follicles may play an important part in the initiation of the lesions. [25, 83] Follicular occlusion was found in all specimens compared with controls and regardless of disease duration. [38] Folliculitis and perifollicular inflammation are common and occur in about two thirds of cases, with or without follicular occlusion.
The earliest inflammatory event is a segmental rupture of the follicular epithelium, followed by spilling of foreign body material. The apocrine glands are not involved in the earliest stage of follicular hyperkeratosis and infundibulofolliculitis. [51]
The inflammatory infiltrate is composed of neutrophils, lymphocytes, plasma cells, and, occasionally, eosinophils. Active inflammation around the sweat glands is less common than inflammation around the hair follicles. The histologic features reveal inflammation of the apocrine glands in only 33% of cases. Apocrinitis only evolves by extension of the inflammatory process. [41] Apocrine gland destruction by neutrophils is occasionally observed. Abscess formation occurs, leading to destruction of the pilosebaceous unit and, eventually, the other adnexal structures. Apoeccrine glands (present in axillae), which drain directly on the epidermal surface, appear intact and not inflamed. [13]
Chronic lesions have a dermis with an inflammatory cell infiltrate and foreign body–type granulomas around the hair follicles and the sinus tracts. The presence of epithelioid granulomas in so-called granulomatous hidradenitis suppurativa should alert to the possibility of coexisting granulomatous disease, such as Crohn disease or sarcoidosis. [62]
The draining sinus tracts extend predominantly into the dermis and are lined by a variably thickened stratified epithelium; they extend in the form of dissecting tracts, which burrow through the necrotic tissue. The epithelium is constantly breaking down; therefore, the sinus tract is not completely lined with epithelium. [84] As previously mentioned, the 3 phenotypes (see Other Tests) of stratified squamous epithelia reflect the dynamic processes of inflammation, proliferation, and stratification that occur in hidradenitis suppurativa. [79]
Lipid rafts (membrane microdomains composed of cholesterol and gangliosides) have been described and appear to have potentially relevant functions in the formation of sinus tracts. The lipid rafts provide anchor points for growth factor receptors and are expressed on migrating cells such as keratinocytes involved in wound healing. Thus, sinus tract formation may represent an aberrant epidermal repair response executed by the lipid raft-enriched stem cell–like keratinocytes in the epidermis and hair follicles, as well as in sinus tracts in hidradenitis suppurativa, that emerge due to the influence of local inflammatory cytokines and are capable of nonmalignant infiltrative growth in the dermis and subcutis. [85]
With regard to the expression of CK19 in type II epithelium and overlying epidermis in hidradenitis suppurativa lesions (which can also be induced in epidermal keratinocytes grown in organotypic culture medium with the addition of retinoic acid), study of the expression of retinoic acid and retinoid X receptors in the different epithelial phenotypes of the draining sinus would be interesting.
Retinoids are known to induce a differentiation shift in keratinocytes, which thereby acquire certain features of simple glandular epithelia. Type III epithelium expresses some markers of such epithelia. This finding may be interpreted as a kind of metaplasia toward glandular differentiation. [79] Free hair shafts can be found in the sinus and surrounding dermis, without apparent connection to the epithelium.
Difficulty may arise in distinguishing well-differentiated squamous cell carcinoma (SCC) and florid pseudoepitheliomatous hyperplasia. Pseudoepitheliomatous hyperplasia is usually associated with chronic irritation, unlike SCC. Tissue destruction, necrosis, and, often, keratin pearls, are associated with SCCs. Vascular and lymphatic invasion may be present in SCC. Mitotic activity is seen in both conditions, although abnormal mitoses are only seen in SCCs.
Staging
Clinical staging of hidradenitis suppurativa has diagnostic value. A study has shown that the soluble IL-2 receptor serum level in patients with hidradenitis suppurativa can be used as valuable marker for disease staging. [86] The Hurley clinical staging of hidradenitis suppurativa from 1989 is still relevant today; it has diagnostic value but is not suitable for monitoring the efficacy of interventions in clinical trials. [1] It is as follows:
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First stage: Solitary/multiple, isolated abscess formation without scarring or sinus tracts
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Second stage: Recurrent abscesses, single/multiple widely separated lesions, with sinus tract formation and cicatrization
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Third stage: Diffuse/broad involvement or multiple interconnected sinus tracts/abscesses across the entire area
Dynamic staging system have been used for assessing differences in treatment effects. [6] Uniform outcome variables should take into account the known characteristics of hidradenitis suppurativa, including the following: [6]
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Anatomical region involved (axilla, groin, genital, gluteal, or other inflammatory region left and/or right) - Three points per region involved
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Number and scores of lesions (abscesses, nodules, fistulas, scars) - Two points for each nodule, 4 points for each fistulas, 1 point for each scar, 1 point for each "other"
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The longest distance between 2 relevant lesions, ie, nodules and fistulas, in each region, or size if only 1 lesion - Less than 5 cm, 2 points; less than 10 cm, 4 points; more than 10 cm, 8 points
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Lesions are clearly separated by normal skin in each region - If yes, 0 points; if no, 6 points.
A six-stage physician global assessment (PGA) is defined as follows:
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Clear: No inflammatory or noninflammatory nodules
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Minimal: Only the presence of noninflammatory nodules
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Mild: Fewer than five inflammatory nodules or one abscess or draining fistula and no inflammatory nodules
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Moderate: Fewer than five inflammatory nodules or one abscess or draining fistula and one or more inflammatory nodules or 2-5 abscesses or draining fistulas and fewer than 10 inflammatory nodules
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Severe: Two to five abscesses or draining fistulas and 10 or more inflammatory nodules
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Very severe: More than five abscesses or draining fistulas
However, a Hurley severity grade‒relevant conservative and surgical treatment for hidradenitis suppurativa is recommended. [1, 7] In order to assess any treatment effectiveness, it is very important to standardize relevant endpoints. Defined as at least a 50% reduction in total abscess and inflammatory nodule count with no increase in abscess count and no increase in draining fistula count relative to baseline at week 12, the hidradenitis suppurativa clinical response (HiSCR) is currently the most appropriate clinical endpoint to assess treatment and effectiveness for hidradenitis suppurativa treatment. It does not contradict hidradenitis suppurativa response measured by the modified Sartorius Score or PGA, but rather represents a more sensitive measure of change in disease activity, resulting in a more accurate representation of patient response and treatment evaluation. The HiSCR does not take into account the size or severity of individual lesions and does not measure how treatment response affects a patient’s level of pain or quality of life. However, the threshold of 50% reduction in total abscess and inflammatory nodule count is the defined level that is clinically appropriate and meaningful to the patient regarding improvement in quality of life and pain level. [8]
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Vulvar hidradenitis suppurativa.
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Vulvar and inguinal indurations.
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Sinus tract.
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Draining sinus tract.
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Axillary hidradenitis suppurativa in a patient with pyoderma gangrenosum.
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Close-up view of axillary hidradenitis suppurativa in a patient with pyoderma gangrenosum.
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Submammary hidradenitis suppurativa in a patient with pyoderma gangrenosum.
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Double-ended-comedones. Hidradenitis suppurativa in a patient with pyoderma gangrenosum.
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Inguinal hidradenitis suppurativa in a patient with pyoderma gangrenosum.
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Close-up view of inguinal hidradenitis suppurativa in a patient with pyoderma gangrenosum.
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Pyoderma gangrenosum in a patient with hidradenitis suppurativa.
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Close-up view of pyoderma gangrenosum in a patient with hidradenitis suppurativa.
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Coexisting hidradenitis suppurativa and pyoderma gangrenosum.
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Coexisting hidradenitis suppurativa and pyoderma gangrenosum.
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Hidradenitis suppurativa in a patient with pyoderma gangrenosum.
