Ultrasound Evaluation as a Complementary Test in Hidradenitis Suppurativa: Proposal of a Standarized Report

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1 Ultrasound Evaluation as a Complementary Test in Hidradenitis Suppurativa: Proposal of a Standarized Report Antonio Martorell, MD, PhD,* Ximena Wortsman, MD, Fernando Alfageme, MD, Gaston Roustan, MD, Salvador Arias-Santiago, MD, x Orlando Catalano, MD, k Maria Scotto di Santolo, MD, Kian Zarchi, MD, # Marcio Bouer, MD,** Diana Gaitini, MD, Claudia Gonzalez, MD, Robert Bard, MD, xx F. Javier García-Martínez, MD, kk and Anitha Mandava, MD BACKGROUND Staging and monitoring of patients with hidradenitis suppurativa (HS) have been traditionally based on clinical findings. However, the physical examination may show important limitations because of its poor sensitivity for differentiating between different lesion subtypes, and its low sensitivity to define the disease s activity. OBJECTIVE To develop a consensus ultrasound (US) report that could summarize the relevant anatomical characteristics and staging of patients considering the experience of radiologists and dermatologists working on imaging of HS. METHODS A questionnaire on different aspects related to US examination in HS was performed. A working group, called DERMUS, composed of doctors from 9 countries who have been working in dermatologic US applied in patients with HS on a regular basis were included to evaluate the different items provided. RESULTS A consensus US report to evaluate HS patients was established. CONCLUSION The authors present the first attempt to define a HS standardized sonographic report. This model would be the first effort to include this imaging technique as the first elective medical test for staging and monitoring patients, which can support therapeutic decisions by providing earlier, objective, deeper, anatomical, and comparative evaluations in this difficult to treat disease. The authors have indicated no significant interest with commercial supporters. Hidradenitis suppurativa (HS), historically called as Verneuil disease, has been defined as a recurrent, debilitating chronic inflammatory skin disease that typically presents after puberty with deep, inflammatory, painful in apocrine glandbearing parts of the body. 1,2 Diagnostic and staging criteria for HS have been traditionally based on clinical findings, as in the Hurley classification, 3 the most commonly used for disease staging. The latter clinical scoring relies solely on the lesional characteristics and extent detected on the physical examination. *Department of Dermatology, Hospital de Manises, Valencia, Spain; Departments of Radiology and Dermatology, Institute for Diagnostic Imaging and Research of the Skin and Soft Tissues, Clinica Servet, Faculty of Medicine, University of Chile, Santiago, Chile; Department of Dermatology, Hospital Puerta del Hierro, Majahonda, Madrid, Spain; x Department of Dermatology, Virgen de las Nieves University Hospital, Granada, Spain; k Department of Radiology, National Cancer Institute Fondazione Pascale, Naples, Italy; Department of Radiology, Università degli studi di Napoli, Naples, Italy; # Department of Dermatology, Roskilde Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; **Department of Radiology, Affiliation Hospital das Clínicas da Faculdade de Medicina de São Paulo, Brazil; Department of Medical Imaging, Rambam Health Care Centre, Haifa, Israel; Department of Radiology, IDIME Instituto de Imágenes Diagnósticas, Bogota, Colombia; xx Bard Cancer Center, New York, New York; kk Department of Dermatology, Clínica Universidad de Navarra, Madrid, Spain; Department of Radiodiagnosis, Central Hospital, South Central Railway, Telangana, India 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: Dermatol Surg 2017;0:1 9 DOI: /DSS

2 ULTRASOUND EVALUATION IN HIDRADENITIS SUPPURATIVA However, the clinical examination may show important limitations in the staging of patients. 3 Palpation may have low sensitivity because it can be imprecise for the diagnosis of nodules, sinuses, or fistulous tracts, which are critical determinations for the assessment of severity of HS according to the clinical criteria. It is also difficult to recognize clinically the difference between a draining abscess and a draining fistula or the true extent of inflammatory edema. The presence of fistulous tracts or recurrent fluid collections usually requires modification of treatment from medical to surgical. 4 Recently, the usefulness of ultrasound (US) as a noninvasive imaging technique that allows us to better understand HS as a pathology with subclinical anatomical manifestations impossible to deduct from the clinical examination has been described. 3 5 In this point, Wortsman and colleagues 3 based on a prospective case series of patients with HS, concluded that clinical examination alone usually underestimates the severity and disease involvement of HS. This assessment, that was associated with a high percentage (82%) of management modification for patients after the US examination, including 24% of cases that changed from medical to surgical management, suggested that this technique could be useful for HS. These data have been corroborated by later studies presented by Martorell and Segura, 5 which obtained similar results. Because US seems to be a promising medical test to better evaluate the severity and to improve the objective follow-up of a patient with HS, the development of a standardized consensus US report may be needed. The aim of this study was to develop a consensus color Doppler (CD) US report that could summary the relevant anatomical characteristics and staging of patients considering the experience of radiologists and dermatologists working on imaging of HS. Material and Methods An international medical group, called DERMUS (Dermatologic Ultrasound), composed of 14 physicians (9 males and 5 females; 8 radiologists and 6 dermatologists) from 9 countries (Spain, Italy, Chile, Brazil, USA, Colombia, Denmark, Israel, and India) representing 3 continents (Europe, America, and Asia) who have been working and publishing 7 in dermatologic US on a regular basis were included. Currently, all the group members work with CD multichannel ultrasound machines and high and variable frequency probes that range in their upper frequency between 15 MHz and 22 MHz. A questionnaire on different aspects related to the US examination in patients wih HS was delivered by to all of them. The deadline for answering was 10 days after receipt. The areas of discussion included critical points that might be described in the report such as technical aspects, operator in charge of performing the examination, regions included in the study, key lesion definitions (Tables 1 and 2), 6 10 and characteristics such as size, location, supplemental and relevant anatomical information, usage of CD and spectral curve analysis, and the best times for performing a sonographic staging. The article, its recommendations and discussion were reviewed and approved by all participants. Hence, the final HS sonographic report was based on the majority vote of the group, which had to receive over 70% approval of the group to become agreed suggestions. TABLE 1. Clinical Key Lesions in Hidradenitis Suppurativa Type Definition Nodule Solid, erythematous, firm, pyogenic granuloma-like, round lesion #2 cm located in skin or subcutaneous tissue (Figure 1A). 6 Abscess Fluctuating, draining or not, erythematous, soft or painful to touch/spontaneously painful, round lesion >2 cm (Figure 2A). 6 Fistula Tunnel of variable length with a skin opening and sometimes oozing a fluid 7 (Figure 3A). Multitunnel: the presence of numerous and/ or communicated tunnels in the same corporal region. 7 2 DERMATOLOGIC SURGERY

3 MARTORELL ET AL TABLE 2. Sonographic Key Lesions in Hidradenitis Suppurativa TABLE 3. Data Distribution and Recommendations Type Definition n (%) Pseudocyst Fluid collection Fistulous tract Connected fistulous tracts Hair tracts Results Round or oval shaped hypoechoic or anechoic nodular dermal and/ or hypodermal structure (#1 cm) Hypoechoic or anechoic fluid dermal and/or hypodermal saclike structure connected to the base of widened hair follicles Hypoechoic or anechoic dermal and/or hypodermal band-like structure connected to the base of widened hair follicles Two or more connected fistulous tracts in the same region Hyperechoic mono or bilaminar linear fragments within the pseudocysts, fluid collections, or fistulous tracts Fourteen questionnaires from 9 countries were received and analyzed (Table 3). The specialties of the participants in the group were 57% radiology (n =8) and 43% dermatology (n = 6). Regarding the elementary lesion definitions, 93% of the group agreed in considering the descriptions included in the Table 2 as acceptable to be used in the US analysis of HS. Ninety-three percent of the experts considered that the HS report would include all the 3 lesion subtypes (pseudocysts, fluid collections, and fistulous tracts). More detailed descriptions that include the connection of fistulous tracts and the hair tracts present within the fluid collections and fistulous tracts 4,8,9 were approved by 86% and 79% of experts, respectively (Table 3 and Figures 1 4). Ninety-three percent of the panel experts considered that all the key would be described in the final HS report. As regards the measurements of the, 86% considered necessary to measure major axes and thickness of each lesion. Regarding what type of need to be measured, 57% considered that all the key types will be included, in contrast with 43% of experts, who thought that only fluid collections and General Data No. Participants 14 Countries 9 Specialties Radiology 8 (57) Dermatology 6 (43) Range hidradenitis suppurativa examinations/mo (mean) General aspects for performing hidradenitis suppurativa ultrasound examination On hidradenitis suppurativa key definitions Pseudocyst: round or oval shaped hypoechoic or anechoic nodular dermal or hypodermal structure Fluid collection: hypoechoic or anechoic fluid dermal or hypodermal deposits connected to the base of widened hair follicles Fistulous tract: hypoechoic or anechoic band-like dermal or hypodermal structure dermal connected to the base of widened hair follicles 3 35 (mean 9, 92) 13 (93) 13 (93) 13 (93) Reporting the presence of key Only pseudocysts 0 (0) Only fluid collections 0 (0) Only fistulous tracts 0 (0) Only fluid collections and fistulous 1 (7) tracts All key in the report 13 (93) (pseudocysts, fluid collections, and fistulous tracts) On reporting complexity of the key hidradenitis suppurativa Connected fistulous tracts (i.e., 2 or more connected fistulous tracts in the same region) Hair tract presence: hyperechoic mono or bilaminar linear fragments within the pseudocysts, fluid collections, or fistulous tracts 12 (86) 11 (79) On reporting counting key in the report All key 13 (93) Just pseudocysts 0 (0) Just fluid collections 0 (0) Just fistulous tracts 0 (0) Just fluid collections and fistulous 1 (7) tracts No counting 0 (0) 0:0:MONTH

4 ULTRASOUND EVALUATION IN HIDRADENITIS SUPPURATIVA TABLE 3. (Continued) TABLE 3. (Continued) n (%) On reporting measurements of the key Only major diameter axes 0 (0) Only thickness 0 (0) Major axes and thickness 12 (86) No measurements 2 (14) On key that should be measured All 8 (57) Only pseudocysts 0 (0) Only fluid collections 0 (0) Only fistulous tracts 0 (0) Only fluid collections and 6 (43) pseudocysts On reporting layer location (dermal and hypodermal) Reported for all key 12 (86) Only reported for fluid collections 2 (14) and fistulous tracts On reporting regional lymph nodes Presence 14 (100) Diameter 13 (93) Cortical thickening 6 (43) On areas included on the ultrasound examination Only clinical affected areas 3 (21) Only axillary and groin regions 1 (9) (bilateral) Both axillary and groin regions plus any 10 (71) other symptomatic or clinical region On assessing vascularity of the key Always use color Doppler on the 14 (100) examination Always use spectral curve analysis in 4 (29) the examination Both color Doppler and spectral 3 (21) curve analysis for studying all key Color Doppler and spectral curve analysis only for studying fluid collections and fistulous tracts (major ) Always measure thickness of 3 main vessels in the periphery of fluid collections and fistulous tracts Always report type of vascularity (arterial or venous) in the periphery of the key or major 7 (50) 2 (14) 10 (71) Always report peak systolic velocity in the periphery of the key or major Always report the presence or absence of increased blood flow in the periphery of the key or major n (%) 5 (35) 10 (71) On sonographic staging hidradenitis suppurativa Only stage at first examination 1 (9) Stage before and after a period of 2 (14) treatment or a surgery Staging at all ultrasound 11 (79) examinations Never perform sonographic staging 0 (0) Formal hidradenitis suppurativa report Always 11 (79) Only for severe cases 0 (0) Only basal for treatment cases 0 (0) Only for presurgical cases 0 (0) For before and after treatment 1 (9) examinations No formal report, just a comment on 2 (14) the chart pseudocysts would be sized. Evaluation of layer location was considered necessary for all key by 86% of the panel experts. Lymph node presence was considered to be included in the report by all the experts. Ninety-three percent considered also important to include their diameter. Only 43% of participants included the cortical thickening measure. Seventy percent of experts considered that both axillary and groin regions plus any other symptomatic or clinical region would be evaluated in all HS cases. A limited examination only circumscribed to symptomatic areas and only of both axillar and groin areas were considered by 21% and 9% of experts, respectively. The routine use of CD was recommended by 100%. The detailed evaluation of blood flow with spectral curve analysis (type and velocity [cm/s] of blood flow) in the periphery of the key (fluid collections and fistulous tracts) was approved by 71% of experts. 4 DERMATOLOGIC SURGERY

5 MARTORELL ET AL Figure 1. (A) Clinical nodule (yellow arrow). (B) Gray scale ultrasound shows an oval shaped anechoic nodular dermal structure suggestive of pseudocyst. Seventy-nine percent of specialists considered that a sonographic staging evaluation should be performed at all examinations, 14% considered adequate to do it before and after a period of treatment or a surgery, and 9% requested the US staging only at the first visit. Seventy-nine percent of experts considered it mandatory to prepare a formal report for each visit to the specialist. Fourteen percent of them considered that just a comment on the chart would be enough. Finally, 9% of experts considered a formal report only for before and after treatment examinations. A CD US summary HS report template was prepared according to the results (Table 4). Discussion Hidradenitis suppurativa is currently considered a prevalent disease, with rates of between 1% and 4%, 11 with autoimmune and genetic backgrounds and chronic inflammatory activity that according to imaging information usually involves both the dermal and hypodermal layers and shows subclinical alterations 2,12 Current staging, inflammatory activity, and follow-up evaluation systems are only based on the physical examination of those clinical or palpable. In this sense, different models for classifying and staging HS have been described, including qualitative models, such as the Hurley staging system, 13,14 and quantitative models, such as the Sartorius and the modified Sartorius systems, the Hidradenitis Suppurativa Physician Global Assessment (HS-PGA). 13,15 17 In the same way, the Hidradenitis Suppurativa Clinical Response (HiSCR) was recently validated and designed to clinically quantify disease severity and establish a meaningful clinical endpoint. 18 However, there are several factors that limit the value of a clinical evaluation or scoring examination to assess the real severity and activity in HS. First, as in other dermal or subdermal diseases, HS disease seems to present deeper anatomical alterations, and the physical Figure 2. (A) Clinical abscess. (B) Gray scale ultrasound evaluation demonstrates a hypoechoic fluid dermal and hypodermal anechoic fluid collection. (C) Color Doppler ultrasound demonstrates increased vascularity in the periphery suggestive of active inflammation (colors). 0:0:MONTH

6 ULTRASOUND EVALUATION IN HIDRADENITIS SUPPURATIVA Figure 3. (A) Clinical fistula. (B) Gray scale ultrasound shows anechoic band-like dermal structure. (C) Color Doppler ultrasound demonstrates inflammatory activity in the periphery of the lesion (colors). Notice the connection of the tract to the base of widened hair follicles. examination can be only capable to detect large or those that are highly inflamed or clinically represented by erythematous skin areas (Figure 5). This hypothesis was confirmed by Worstman and Jemec 4 and Martorell and Segura, 6 comparing clinical and sonographic evaluations that confirm the existence of significant nonclinically evident that affect patients with HS. Second, the clinical examination may not be capable to adequately differentiate between key lesion types such as fluid collections or fistulous tracts that can imply a modification of the staging and therefore the management (Figure 6). Moreover, this differentiation between elementary can be therapeutically relevant, as Wortsman and colleagues 3 reflected in a past study, in which 82% of cases modified the treatment after the US examination, and 24% of cases changed from medical to surgical management. Third, current response-to-treatment evaluation is only based on the reduction or nonincrease in number of the different clinical (Table 2). However, early anatomical changes may be missed and clinical evaluation can lack enough precision which should be of paramount importance for the tracking of activity in an inflammatory disease such HS. 19 Color Doppler US assessment has been described as relevant and the first choice imaging modality for evaluating HS because it allows improving the precision of both the diagnosis and staging of the disease over time (Figure 6). 18 Nevertheless, the performance of this type of imaging examination requires training of the operator and the standardization of the reports. Regarding the operator, the DERMUS group has previously published in their guidelines 7 that the recommended person in charge of the US examination should be a physician and not a technician. Also, it has been suggested that the operator should be trained on US imaging and dermatologic pathology. These recommendations are based on the Figure 4. (A) Patient with hidradenitis suppurativa with clinical suppurative on his left axilla (B) Gray scale ultrasound demonstrates connected anechoic band-like fistulous tracts in the same region. 6 DERMATOLOGIC SURGERY

7 MARTORELL ET AL TABLE 4. Color Doppler Ultrasound Hidradenitis Suppurativa Summary Report Template need for gathering of the visual and sonographic data for improving the interpretation of the test. Most of radiologists and dermatologists included in the present expert panel recommend US assessment of both axilla and groin areas, regardless of the absence of clinical. This situation fits with previous published data that revealed a high frequency of subclinical in these regions. 4 6,8,9,18 0:0:MONTH

8 ULTRASOUND EVALUATION IN HIDRADENITIS SUPPURATIVA Figure 5. Clinical-sonographic discordance. (A) Clinical nodule and scarring in the left axillary region. (B) Gray scale panoramic view of ultrasound shows a 4.7 cm (long axis) 0.4 cm (short axis) hypoechoic and anechoic fistulous tract running in transverse axis through the left axillary region underneath the erythematous nodule. The hypoechoic laminar bands (*) in the anterior and posterior dermal borders are consistent with scarring in the periphery of the tract. Some hyperechoic linear tracts suggestive of retained fragments (arrowhead) of hair tracts are also detected. (C) Gray scale ultrasound demonstrates connections (arrows) to the widened base of the hair follicles in the surface of the fistulous tract (short axis of the fistula and longitudinal axis of the axilla). (D) Color Doppler ultrasound (long axis of the fistula and transverse axis of the axillary region) demonstrates hypervascularity (colors) in the periphery of the fistulous tract. To establish a common language for both dermatologists and radiologists, the present work offers the first attempt to standardize by providing a specific dermatologic US report oriented to the patient HS and based on the experience of an international group of specialists routinely working on the dermatologic US field. This CD US report (Table 3) considers the US key, which more or less correspond with the clinical evaluation. In this sense, the objective is to achieve a more real score by including both clinical and subclinical. This would be of paramount importance because the current descriptions of the clinical types of key may not be actual synonyms with the sonographic key. For example, in the sonographic study, a clinically diagnosed nodule may represent a pseudocyst, a fluid collection or a fistulous tract. Inversely, a fluid collection detected on US may not necessarily imply an abscess with pus. Moreover, several of these fluid collections can present negative cultures. This may require a redefinition of the current clinical glossary for describing elementary in HS. However, lymph nodes evaluation and analysis of complex structures that are not clinically well defined, including the connection of fistulous tracts or the presence of hair tracts, perhaps may help in the near future on establishing better therapeutic approaches, mainly in patients with Hurley II and Hurley III. Figure 6. Clinical-sonographic discordance. (A) Clinical nodule (blue line). (B) Gray scale ultrasound evaluation demonstrates anechoic band-like dermal fistula (red line in the clinical photograph). (C) Color Doppler ultrasound demonstrates inflammatory activity in the periphery of the lesion (colors). 8 DERMATOLOGIC SURGERY

9 MARTORELL ET AL In the same line, the monitoring and registering of the size of the most representative, and early changes in the lesional blood flow (Doppler activity) of each area, can be useful as key markers of inflammatory activity and may optimize the HS follow-up and assess the response of therapeutic options. 20,21 The main advantages of using a standardized US report for HS are as follows: (1) to optimize the collection of data using a well-defined model, (2) to register characteristics that can be compared in each visit, (3) a better reproducibility of the performance of US examinations considering dermatological and radiological operators, and (4) the provision of data under a similar validated model. The latter facts can support the comparison of objective data between centers distributed worldwide. Sonographic diagnostic criteria and a staging method have been previously reported for HS (SOS-HS) 4 ; therefore, to move forward on the noninvasive registering of the data, the present group of experts provides a proposal for reporting the examinations and describing the anatomical findings. In conclusion, a standardized sonographic report particularly oriented to HS that was performed and approved by the consensus of an international group of radiologists and dermatologists routinely working on dermatologic US is the first attempt to include this imaging technique as the first elective medical test for staging and monitoring patients. This would be the starting point for future works that consider intraobserver or interobserver variabilities. References 1. Verneuil A. Etudes sur les tumeurs de la peau; de quelques mal- adies des glandules sudoripares. Arch Gen Med 1854;4: Martorell A, García-Martínez FJ, Jiménez-Gallo D, Pascual JC, et al. An update on hidradenitis suppurativa (part I): epidemiology, clinical aspects, and definition of disease severity. Actas Dermosifiliogr 2015; 106: Wortsman X, Moreno C, Soto R, Arellano J, et al. Ultrasound in-depth characterization and staging of hidradenitis suppurativa. Dermatol Surg 2013;39: Wortsman X, Jemec GBE. Real-time compound imaging ultrasound of hidradenitis suppurativa. Dermatol Surg 2007;33: Martorell A, Segura Palacios JM. Ultrasound examination of hidradenitis suppurativa. 2015;106(Suppl 1): Zouboulis CC, Del Marmol V, Mrowietz U, Prens EP, et al. Hidradenitis suppurativa/acne inversa: criteria for diagnosis, severity assessment, classification and disease evaluation. Dermatology 2015; 231: Lipsker D, Severac F, Freysz M, Sauleau E, et al. The ABC of hidradenitis suppurativa: a validated glossary on how to name. Dermatology 2016;232: Revuz J. Hidradenitis suppurativa: terminology. Dermatology 2016; 232: Lipsker D. Reply to Revuz Letter entitled hidradenitis suppurativa: terminology. Dermatology 2016;232: Wortsman X. Reply to Lipsker et al. and Revuz on hidradenitis suppurativa terminology: the imaging point of view. Dermatology 2016;232: Jemec GBE. Clinical practice. Hidradenitis suppurativa. N Engl J Med 2012;366: Kurayev A, Ashkar H, Saraiya A, Gottlieb AB. Hidradenitis suppurativa: review of the pathogenesis and treatment. J Drugs Dermatol 2016;15: Zouboulis CC, Desai N, Emtestam L, Hunger RE, et al. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol Venereol 2015;4: Hurley H. Axillary hyperhidrosis, apocrine bromhidrosis, hidradenitis suppurativa and familial benign pemphigus. Surgical approach. In: Roenigk R, Roenigk HJ, editors. Dermatologic Surgery Principles and Practice (2nd ed). New York, NY: Marcel Dekker, Inc.; 1996; p Sartorius K, Emtestam L, Jemec GBE, Lapins J. Objective scoring of hidradenitis suppurativa reflecting the role of tobacco smoking and obesity. Br J Dermatol 2009;161: Revuz J. Modifications to the Sartorius score and instructions for evaluating the severity of suppurative hidradenitis [in French]. Ann Dermatol Venereol 2007;134: Sartorius K, Killasli H, Heilborn J, Jemec GBE, et al. Interobserver variability of clinical scores in hidradenitis suppurativa is low. Br J Dermatol 2010;162: Kimball AB, Sobell JM, Zouboulis CC, Gu Y, et al. HiSCR (Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo-controlled portion of a phase 2 adalimumab study. J Eur Acad Dermatol Venereol 2016;30: Martorell A. Caracterisiticas ecográficas de patologia inflamatoria cutánea. Actual Med 2015;792(Suppl 2): Naredo E, Valor L, De La Torre I, Martínez-Barrio J, et al. Ultrasound joint inflammation in rheumatoid arthritis in clinical remission: how many and which joints should be assessed? Arthritis Care Res (Hoboken) 2013;65: Janta I, Valor L, De la Torre I, Martínez-Estupiñán L, et al. Ultrasounddetected activity in rheumatoid arthritis on methotrexate therapy: which joints and tendons should be assessed to predict unstable remission? Rheumatol Int 2016;36: Address correspondence and reprint requests to: Antonio Martorell, MD, PhD, Department of Dermatology, Hospital de Manises, Avenida Generalitat 50, Valencia, Spain, or antmarto@hotmail.com 0:0:MONTH