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Squamous Cell Carcinoma in Hidradenitis Suppurativa Lesions Following Tumor Necrosis Factor α Inhibitors

Article Type
Changed
Fri, 08/13/2021 - 09:15

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with high morbidity rates. Symptoms typically develop between puberty and the third decade of life, affecting twice as many females as males, with an overall disease prevalence of 1% to 4%.1 The pathogenesis is theorized to be related to an immune response to follicular occlusion and rupture in genetically susceptible individuals.

Among the complications associated with HS, the development of cutaneous squamous cell carcinoma (SCC) is 4.6-times more likely within HS lesions than in normal skin and typically is seen in the setting of long-standing disease, particularly in men with HS lesions located on the buttocks and genital region for more than 20 years.2 In 2015, the tumor necrosis factor (TNF) inhibitor adalimumab was approved by the US Food and Drug Administration for the treatment of HS. Tumor necrosis factor α inhibitors have been associated with an increased risk for skin cancer in other clinical settings.3,4 We present a case of locally advanced SCC that developed in a patient with HS who was treated with adalimumab and infliximab (both TNF-α inhibitors), ultimately leading to the patient’s death.

A 59-year-old man who smoked with a 40-year history of severe HS, who previously was lost to follow-up, presented to our dermatology clinic with lesions on the buttocks. Physical examination demonstrated confluent, indurated, boggy plaques; scattered sinus tracts with purulent drainage; scattered cystlike nodules; and tenderness to palpation consistent with Hurley stage III disease (Figure 1A). No involvement of the axillae or groin was noted. He was started on doxycycline and a prednisone taper with minimal improvement and subsequently was switched to adalimumab 3 months later. Adalimumab provided little relief and was discontinued; therapy was transitioned to infliximab 3 months later.

Figure 1. Hidradenitis suppurativa with squamous cell carcinoma (SCC) transformation. A, Three months prior to initiation of tumor necrosis factor (TNF) α antagonist therapy, clinical examination showed Hurley stage III disease. B, Five months after initiation of TNF-α antagonist therapy, deep ulceration and indurated nodules of the left buttock were present, consistent with SCC.


The patient returned to our clinic 3 months later with a severe flare and intractable pain after 4 infusions of infliximab. Physical examination showed a 7×5-cm deep malodorous ulcer with fibrinous exudate on the left buttock, several 2- to 3-cm shallow ulcers draining yellow exudate, and numerous fluctuant subcutaneous nodules on a background of scarring and sinus tracts. He was started again on doxycycline and a prednisone taper. At follow-up 2 weeks later, the largest ulcer had increased to 8 cm, and more indurated and tender subcutaneous nodules and scattered ulcerations developed (Figure 1B). Two punch biopsies of the left buttock revealed an invasive keratinizing carcinoma with no connection to the epidermis, consistent with SCC (Figure 2). Human papillomavirus (HPV) test results with probes for 37 HPV types—13 that were high risk (HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68)—were negative. Computerized tomography demonstrated diffuse thickening of the skin on the buttocks, inguinal adenopathy suspicious for nodal metastases, and no evidence of distant metastatic disease. Given the extent of the disease, surgical treatment was not an option, and he began receiving palliative radiotherapy. However, his health declined, and he developed aspiration pneumonia and hypotension requiring pressor support. He was transitioned to hospice care and died 3 months after presentation.

Figure 2. Biopsy results showed an infiltrating keratinizing carcinoma consistent with moderately differentiated squamous cell carcinoma (H&E, original magnification ×100).


Tumor necrosis factor α antagonist treatment is being increasingly used to control HS but also may increase the risk for SCC development. We performed a search of PubMed articles indexed for MEDLINE as well as Web of Science using the terms hidradenitis suppurativa or acne inversa and one of the following—tumor necrosis factor inhibitor, infliximab, adalimumab, or etanercept—and squamous cell carcinoma or Marjolin ulcer. Seven cases of SCC arising in an HS patient treated with a TNF-α inhibitor have been reported (Table).5-10 Four cases were associated with infliximab use, 2 with adalimumab, and our case occurred after both adalimumab and infliximab treatment. All individuals were men with severe, long-standing disease of the anogenital region. In addition to smoking, HPV-16 positivity also has been reported as a risk factor for developing SCC in the setting of HS.11 In our patient, however, HPV testing did not cover all HPV strains, but several high-risk strains, including HPV-16, were negative.



Hidradenitis suppurativa is caused by an immune response to ruptured follicles and TNF-α antagonists are useful in suppressing this response; however, immunosuppression can lead to an increased susceptibility to malignancy, especially in SCC. It is unclear whether the use of infliximab or adalimumab is causal, additive, or a confounder in the development of SCC in patients with severe HS. It is possible that these agents increase the rapidity of the development of SCC in already-susceptible patients. Although TNF-α antagonists can be an effective therapeutic option for patients with moderate to severe HS, the potential risk for contributing to skin cancer development should raise provider suspicion in high-risk patients. Given the findings in this report, it may be suitable for providers to consider a biopsy prior to initiating TNF-α therapy in men older than 20 years with moderate to severe HS of the groin or buttocks, in addition to more frequent monitoring and a lower threshold to biopsy lesions with rapid growth or ulceration.

References
  1. Alikhan A, Lynch PJ, Eisen DB. Hidradenitis suppurativa: a comprehensive review. J Am Acad Dermatol. 2009;60:539-561; quiz 562-533.
  2. Lapins J, Ye W, Nyren O, et al. Incidence of cancer among patients with hidradenitis suppurativa. Arch Dermatol. 2001;137:730-734.
  3. Askling J, Fahrbach K, Nordstrom B, et al. Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data. Pharmacoepidemiol Drug Saf. 2011;20:119-130.
  4. Mariette X, Matucci-Cerinic M, Pavelka K, et al. Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis. Ann Rheum Dis. 2011;70:1895-1904.
  5. Maalouf E, Faye O, Poli F, et al. Fatal epidermoid carcinoma in hidradenitis suppurativa following treatment with infliximab. Ann Dermatol Venereol. 2006;133(5 pt 1):473-474.
  6. Kurokawa I, Nishimura K, Yamanaka K, et al. Cytokeratin expression in squamous cell carcinoma arising from hidradenitis suppurativa (acne inversa). J Cutan Pathol. 2007;34:675-678.
  7. Scheinfeld N. A case of a patient with stage III familial hidradenitis suppurativa treated with 3 courses of infliximab and died of metastatic squamous cell carcinoma. Dermatol Online J. 2014;20(3).
  8. Verdelli A, Antiga E, Bonciani D, et al. A fatal case of hidradenitis suppurativa associated with sepsis and squamous cell carcinoma. Int J Dermatol. 2016;55:E52-E53.
  9. Giesey R, Delost GR, Honaker J, et al. Metastatic squamous cell carcinoma in a patient treated with adalimumab for hidradenitis suppurativa. JAAD Case Rep. 2017;3:489-491.
  10. Roy C, Roy S, Ghazawi F, et al. Cutaneous squamous cell carcinoma arising in hidradenitis suppurativa: a case report. SAGE Open Med Case Rep. 2019;7:2050313X19847359.
  11. Lavogiez C, Delaporte E, Darras-Vercambre S, et al. Clinicopathological study of 13 cases of squamous cell carcinoma complicating hidradenitis suppurativa. Dermatology. 2010;220:147-153.
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Dr. Cooper is from the Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire. Drs. Cowdrey, Linos, and Lefferts are from the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. Dr. Cowdrey is from the Section of Dermatology, and Drs. Linos and Lefferts are from the Department of Pathology and Laboratory Medicine, Dermatopathology Division. Dr. Basic is from the James A. Haley Veterans Hospital, Tampa, and the Department of Dermatology, Morsani College of Medicine, University of South Florida, Tampa.

The authors report no conflict of interest.

Correspondence: Katherina K. Basic, MD, Department of Dermatology, 12901 Bruce B Downs Blvd, Tampa, FL 33612 ([email protected]).

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Dr. Cooper is from the Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire. Drs. Cowdrey, Linos, and Lefferts are from the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. Dr. Cowdrey is from the Section of Dermatology, and Drs. Linos and Lefferts are from the Department of Pathology and Laboratory Medicine, Dermatopathology Division. Dr. Basic is from the James A. Haley Veterans Hospital, Tampa, and the Department of Dermatology, Morsani College of Medicine, University of South Florida, Tampa.

The authors report no conflict of interest.

Correspondence: Katherina K. Basic, MD, Department of Dermatology, 12901 Bruce B Downs Blvd, Tampa, FL 33612 ([email protected]).

Author and Disclosure Information

Dr. Cooper is from the Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire. Drs. Cowdrey, Linos, and Lefferts are from the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. Dr. Cowdrey is from the Section of Dermatology, and Drs. Linos and Lefferts are from the Department of Pathology and Laboratory Medicine, Dermatopathology Division. Dr. Basic is from the James A. Haley Veterans Hospital, Tampa, and the Department of Dermatology, Morsani College of Medicine, University of South Florida, Tampa.

The authors report no conflict of interest.

Correspondence: Katherina K. Basic, MD, Department of Dermatology, 12901 Bruce B Downs Blvd, Tampa, FL 33612 ([email protected]).

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To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with high morbidity rates. Symptoms typically develop between puberty and the third decade of life, affecting twice as many females as males, with an overall disease prevalence of 1% to 4%.1 The pathogenesis is theorized to be related to an immune response to follicular occlusion and rupture in genetically susceptible individuals.

Among the complications associated with HS, the development of cutaneous squamous cell carcinoma (SCC) is 4.6-times more likely within HS lesions than in normal skin and typically is seen in the setting of long-standing disease, particularly in men with HS lesions located on the buttocks and genital region for more than 20 years.2 In 2015, the tumor necrosis factor (TNF) inhibitor adalimumab was approved by the US Food and Drug Administration for the treatment of HS. Tumor necrosis factor α inhibitors have been associated with an increased risk for skin cancer in other clinical settings.3,4 We present a case of locally advanced SCC that developed in a patient with HS who was treated with adalimumab and infliximab (both TNF-α inhibitors), ultimately leading to the patient’s death.

A 59-year-old man who smoked with a 40-year history of severe HS, who previously was lost to follow-up, presented to our dermatology clinic with lesions on the buttocks. Physical examination demonstrated confluent, indurated, boggy plaques; scattered sinus tracts with purulent drainage; scattered cystlike nodules; and tenderness to palpation consistent with Hurley stage III disease (Figure 1A). No involvement of the axillae or groin was noted. He was started on doxycycline and a prednisone taper with minimal improvement and subsequently was switched to adalimumab 3 months later. Adalimumab provided little relief and was discontinued; therapy was transitioned to infliximab 3 months later.

Figure 1. Hidradenitis suppurativa with squamous cell carcinoma (SCC) transformation. A, Three months prior to initiation of tumor necrosis factor (TNF) α antagonist therapy, clinical examination showed Hurley stage III disease. B, Five months after initiation of TNF-α antagonist therapy, deep ulceration and indurated nodules of the left buttock were present, consistent with SCC.


The patient returned to our clinic 3 months later with a severe flare and intractable pain after 4 infusions of infliximab. Physical examination showed a 7×5-cm deep malodorous ulcer with fibrinous exudate on the left buttock, several 2- to 3-cm shallow ulcers draining yellow exudate, and numerous fluctuant subcutaneous nodules on a background of scarring and sinus tracts. He was started again on doxycycline and a prednisone taper. At follow-up 2 weeks later, the largest ulcer had increased to 8 cm, and more indurated and tender subcutaneous nodules and scattered ulcerations developed (Figure 1B). Two punch biopsies of the left buttock revealed an invasive keratinizing carcinoma with no connection to the epidermis, consistent with SCC (Figure 2). Human papillomavirus (HPV) test results with probes for 37 HPV types—13 that were high risk (HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68)—were negative. Computerized tomography demonstrated diffuse thickening of the skin on the buttocks, inguinal adenopathy suspicious for nodal metastases, and no evidence of distant metastatic disease. Given the extent of the disease, surgical treatment was not an option, and he began receiving palliative radiotherapy. However, his health declined, and he developed aspiration pneumonia and hypotension requiring pressor support. He was transitioned to hospice care and died 3 months after presentation.

Figure 2. Biopsy results showed an infiltrating keratinizing carcinoma consistent with moderately differentiated squamous cell carcinoma (H&E, original magnification ×100).


Tumor necrosis factor α antagonist treatment is being increasingly used to control HS but also may increase the risk for SCC development. We performed a search of PubMed articles indexed for MEDLINE as well as Web of Science using the terms hidradenitis suppurativa or acne inversa and one of the following—tumor necrosis factor inhibitor, infliximab, adalimumab, or etanercept—and squamous cell carcinoma or Marjolin ulcer. Seven cases of SCC arising in an HS patient treated with a TNF-α inhibitor have been reported (Table).5-10 Four cases were associated with infliximab use, 2 with adalimumab, and our case occurred after both adalimumab and infliximab treatment. All individuals were men with severe, long-standing disease of the anogenital region. In addition to smoking, HPV-16 positivity also has been reported as a risk factor for developing SCC in the setting of HS.11 In our patient, however, HPV testing did not cover all HPV strains, but several high-risk strains, including HPV-16, were negative.



Hidradenitis suppurativa is caused by an immune response to ruptured follicles and TNF-α antagonists are useful in suppressing this response; however, immunosuppression can lead to an increased susceptibility to malignancy, especially in SCC. It is unclear whether the use of infliximab or adalimumab is causal, additive, or a confounder in the development of SCC in patients with severe HS. It is possible that these agents increase the rapidity of the development of SCC in already-susceptible patients. Although TNF-α antagonists can be an effective therapeutic option for patients with moderate to severe HS, the potential risk for contributing to skin cancer development should raise provider suspicion in high-risk patients. Given the findings in this report, it may be suitable for providers to consider a biopsy prior to initiating TNF-α therapy in men older than 20 years with moderate to severe HS of the groin or buttocks, in addition to more frequent monitoring and a lower threshold to biopsy lesions with rapid growth or ulceration.

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with high morbidity rates. Symptoms typically develop between puberty and the third decade of life, affecting twice as many females as males, with an overall disease prevalence of 1% to 4%.1 The pathogenesis is theorized to be related to an immune response to follicular occlusion and rupture in genetically susceptible individuals.

Among the complications associated with HS, the development of cutaneous squamous cell carcinoma (SCC) is 4.6-times more likely within HS lesions than in normal skin and typically is seen in the setting of long-standing disease, particularly in men with HS lesions located on the buttocks and genital region for more than 20 years.2 In 2015, the tumor necrosis factor (TNF) inhibitor adalimumab was approved by the US Food and Drug Administration for the treatment of HS. Tumor necrosis factor α inhibitors have been associated with an increased risk for skin cancer in other clinical settings.3,4 We present a case of locally advanced SCC that developed in a patient with HS who was treated with adalimumab and infliximab (both TNF-α inhibitors), ultimately leading to the patient’s death.

A 59-year-old man who smoked with a 40-year history of severe HS, who previously was lost to follow-up, presented to our dermatology clinic with lesions on the buttocks. Physical examination demonstrated confluent, indurated, boggy plaques; scattered sinus tracts with purulent drainage; scattered cystlike nodules; and tenderness to palpation consistent with Hurley stage III disease (Figure 1A). No involvement of the axillae or groin was noted. He was started on doxycycline and a prednisone taper with minimal improvement and subsequently was switched to adalimumab 3 months later. Adalimumab provided little relief and was discontinued; therapy was transitioned to infliximab 3 months later.

Figure 1. Hidradenitis suppurativa with squamous cell carcinoma (SCC) transformation. A, Three months prior to initiation of tumor necrosis factor (TNF) α antagonist therapy, clinical examination showed Hurley stage III disease. B, Five months after initiation of TNF-α antagonist therapy, deep ulceration and indurated nodules of the left buttock were present, consistent with SCC.


The patient returned to our clinic 3 months later with a severe flare and intractable pain after 4 infusions of infliximab. Physical examination showed a 7×5-cm deep malodorous ulcer with fibrinous exudate on the left buttock, several 2- to 3-cm shallow ulcers draining yellow exudate, and numerous fluctuant subcutaneous nodules on a background of scarring and sinus tracts. He was started again on doxycycline and a prednisone taper. At follow-up 2 weeks later, the largest ulcer had increased to 8 cm, and more indurated and tender subcutaneous nodules and scattered ulcerations developed (Figure 1B). Two punch biopsies of the left buttock revealed an invasive keratinizing carcinoma with no connection to the epidermis, consistent with SCC (Figure 2). Human papillomavirus (HPV) test results with probes for 37 HPV types—13 that were high risk (HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68)—were negative. Computerized tomography demonstrated diffuse thickening of the skin on the buttocks, inguinal adenopathy suspicious for nodal metastases, and no evidence of distant metastatic disease. Given the extent of the disease, surgical treatment was not an option, and he began receiving palliative radiotherapy. However, his health declined, and he developed aspiration pneumonia and hypotension requiring pressor support. He was transitioned to hospice care and died 3 months after presentation.

Figure 2. Biopsy results showed an infiltrating keratinizing carcinoma consistent with moderately differentiated squamous cell carcinoma (H&E, original magnification ×100).


Tumor necrosis factor α antagonist treatment is being increasingly used to control HS but also may increase the risk for SCC development. We performed a search of PubMed articles indexed for MEDLINE as well as Web of Science using the terms hidradenitis suppurativa or acne inversa and one of the following—tumor necrosis factor inhibitor, infliximab, adalimumab, or etanercept—and squamous cell carcinoma or Marjolin ulcer. Seven cases of SCC arising in an HS patient treated with a TNF-α inhibitor have been reported (Table).5-10 Four cases were associated with infliximab use, 2 with adalimumab, and our case occurred after both adalimumab and infliximab treatment. All individuals were men with severe, long-standing disease of the anogenital region. In addition to smoking, HPV-16 positivity also has been reported as a risk factor for developing SCC in the setting of HS.11 In our patient, however, HPV testing did not cover all HPV strains, but several high-risk strains, including HPV-16, were negative.



Hidradenitis suppurativa is caused by an immune response to ruptured follicles and TNF-α antagonists are useful in suppressing this response; however, immunosuppression can lead to an increased susceptibility to malignancy, especially in SCC. It is unclear whether the use of infliximab or adalimumab is causal, additive, or a confounder in the development of SCC in patients with severe HS. It is possible that these agents increase the rapidity of the development of SCC in already-susceptible patients. Although TNF-α antagonists can be an effective therapeutic option for patients with moderate to severe HS, the potential risk for contributing to skin cancer development should raise provider suspicion in high-risk patients. Given the findings in this report, it may be suitable for providers to consider a biopsy prior to initiating TNF-α therapy in men older than 20 years with moderate to severe HS of the groin or buttocks, in addition to more frequent monitoring and a lower threshold to biopsy lesions with rapid growth or ulceration.

References
  1. Alikhan A, Lynch PJ, Eisen DB. Hidradenitis suppurativa: a comprehensive review. J Am Acad Dermatol. 2009;60:539-561; quiz 562-533.
  2. Lapins J, Ye W, Nyren O, et al. Incidence of cancer among patients with hidradenitis suppurativa. Arch Dermatol. 2001;137:730-734.
  3. Askling J, Fahrbach K, Nordstrom B, et al. Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data. Pharmacoepidemiol Drug Saf. 2011;20:119-130.
  4. Mariette X, Matucci-Cerinic M, Pavelka K, et al. Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis. Ann Rheum Dis. 2011;70:1895-1904.
  5. Maalouf E, Faye O, Poli F, et al. Fatal epidermoid carcinoma in hidradenitis suppurativa following treatment with infliximab. Ann Dermatol Venereol. 2006;133(5 pt 1):473-474.
  6. Kurokawa I, Nishimura K, Yamanaka K, et al. Cytokeratin expression in squamous cell carcinoma arising from hidradenitis suppurativa (acne inversa). J Cutan Pathol. 2007;34:675-678.
  7. Scheinfeld N. A case of a patient with stage III familial hidradenitis suppurativa treated with 3 courses of infliximab and died of metastatic squamous cell carcinoma. Dermatol Online J. 2014;20(3).
  8. Verdelli A, Antiga E, Bonciani D, et al. A fatal case of hidradenitis suppurativa associated with sepsis and squamous cell carcinoma. Int J Dermatol. 2016;55:E52-E53.
  9. Giesey R, Delost GR, Honaker J, et al. Metastatic squamous cell carcinoma in a patient treated with adalimumab for hidradenitis suppurativa. JAAD Case Rep. 2017;3:489-491.
  10. Roy C, Roy S, Ghazawi F, et al. Cutaneous squamous cell carcinoma arising in hidradenitis suppurativa: a case report. SAGE Open Med Case Rep. 2019;7:2050313X19847359.
  11. Lavogiez C, Delaporte E, Darras-Vercambre S, et al. Clinicopathological study of 13 cases of squamous cell carcinoma complicating hidradenitis suppurativa. Dermatology. 2010;220:147-153.
References
  1. Alikhan A, Lynch PJ, Eisen DB. Hidradenitis suppurativa: a comprehensive review. J Am Acad Dermatol. 2009;60:539-561; quiz 562-533.
  2. Lapins J, Ye W, Nyren O, et al. Incidence of cancer among patients with hidradenitis suppurativa. Arch Dermatol. 2001;137:730-734.
  3. Askling J, Fahrbach K, Nordstrom B, et al. Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data. Pharmacoepidemiol Drug Saf. 2011;20:119-130.
  4. Mariette X, Matucci-Cerinic M, Pavelka K, et al. Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis. Ann Rheum Dis. 2011;70:1895-1904.
  5. Maalouf E, Faye O, Poli F, et al. Fatal epidermoid carcinoma in hidradenitis suppurativa following treatment with infliximab. Ann Dermatol Venereol. 2006;133(5 pt 1):473-474.
  6. Kurokawa I, Nishimura K, Yamanaka K, et al. Cytokeratin expression in squamous cell carcinoma arising from hidradenitis suppurativa (acne inversa). J Cutan Pathol. 2007;34:675-678.
  7. Scheinfeld N. A case of a patient with stage III familial hidradenitis suppurativa treated with 3 courses of infliximab and died of metastatic squamous cell carcinoma. Dermatol Online J. 2014;20(3).
  8. Verdelli A, Antiga E, Bonciani D, et al. A fatal case of hidradenitis suppurativa associated with sepsis and squamous cell carcinoma. Int J Dermatol. 2016;55:E52-E53.
  9. Giesey R, Delost GR, Honaker J, et al. Metastatic squamous cell carcinoma in a patient treated with adalimumab for hidradenitis suppurativa. JAAD Case Rep. 2017;3:489-491.
  10. Roy C, Roy S, Ghazawi F, et al. Cutaneous squamous cell carcinoma arising in hidradenitis suppurativa: a case report. SAGE Open Med Case Rep. 2019;7:2050313X19847359.
  11. Lavogiez C, Delaporte E, Darras-Vercambre S, et al. Clinicopathological study of 13 cases of squamous cell carcinoma complicating hidradenitis suppurativa. Dermatology. 2010;220:147-153.
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  • Consider biopsy of representative lesions in men older than 20 years with moderate to severe disease of the groin and/or buttocks prior to initiation of tumor necrosis factor inhibitors.
  • Consider more frequent clinical monitoring with a decrease in threshold to perform biopsy of any new or ulcerating lesions.
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Adalimumab enhances primary wound closure after HS surgery

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Changed
Fri, 04/09/2021 - 08:46

 

Delaying surgical reconstruction of fistula structures until after patients with hidradenitis suppurativa (HS) have been on adalimumab for a minimum of 6 months transforms primary wound closure into a highly attractive option, a pilot study suggests.

“Our experience suggests that under the effects of treatment with adalimumab, wound healing disorders with primary wound closure occur less often. And primary wound closure offers advantages over secondary wound healing: shorter length of inpatient stay, lower morbidity, fewer functional problems, and better quality of life,” Gefion Girbig, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

She noted that primary wound closure following surgery for HS is controversial. For example, current German guidelines recommend complete surgical excision of HS lesions, followed by secondary wound healing; the guidelines advise against primary wound closure. But those guidelines were issued back in 2012, years before adalimumab (Humira) achieved regulatory approval as the first and to date only medication indicated for treatment of HS.

Experts agree that while adalimumab has been a difference maker for many patients with HS, surgery is still often necessary. And many surgeons prefer secondary wound healing in HS. That’s because healing by first intention has historically often resulted in complications involving wound healing disorders and infection. These complications necessitate loosening of the primary closure to permit further wound healing by second intention, with a resultant prolonged healing time, explained Dr. Girbig, of the Institute for Health Sciences Research in Dermatology and Nursing at University Medical Center Hamburg-Eppendorf (Germany).



She and her coinvestigators hypothesized that the disordered wound healing is a consequence of the underlying inflammatory disease that lies at the core of HS, and that quelling the inflammation with adalimumab for at least 6 months before performing surgery with primary closure while the anti-TNF therapy continues would reduce the incidence of wound healing disorders.

This was borne out in the group’s small observational pilot study. It included 10 patients with HS who underwent surgery only after at least 6 months on adalimumab. Six had surgery for axillary HS and four for inguinal disease. Only 2 of the 10 developed a wound healing disorder. Both had surgical reconstruction in the inguinal area. Neither case involved infection. Surgical management entailed opening part of the suture to allow simultaneous secondary wound closure.

This 20% incidence of disordered wound healing when primary closure was carried out while systemic inflammation was controlled via adalimumab is markedly lower than rates reported using primary closure without adalimumab. Dr. Girbig and her coinvestigators are now conducting a larger controlled study to confirm their findings.

She reported having no financial conflicts regarding her study.

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Delaying surgical reconstruction of fistula structures until after patients with hidradenitis suppurativa (HS) have been on adalimumab for a minimum of 6 months transforms primary wound closure into a highly attractive option, a pilot study suggests.

“Our experience suggests that under the effects of treatment with adalimumab, wound healing disorders with primary wound closure occur less often. And primary wound closure offers advantages over secondary wound healing: shorter length of inpatient stay, lower morbidity, fewer functional problems, and better quality of life,” Gefion Girbig, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

She noted that primary wound closure following surgery for HS is controversial. For example, current German guidelines recommend complete surgical excision of HS lesions, followed by secondary wound healing; the guidelines advise against primary wound closure. But those guidelines were issued back in 2012, years before adalimumab (Humira) achieved regulatory approval as the first and to date only medication indicated for treatment of HS.

Experts agree that while adalimumab has been a difference maker for many patients with HS, surgery is still often necessary. And many surgeons prefer secondary wound healing in HS. That’s because healing by first intention has historically often resulted in complications involving wound healing disorders and infection. These complications necessitate loosening of the primary closure to permit further wound healing by second intention, with a resultant prolonged healing time, explained Dr. Girbig, of the Institute for Health Sciences Research in Dermatology and Nursing at University Medical Center Hamburg-Eppendorf (Germany).



She and her coinvestigators hypothesized that the disordered wound healing is a consequence of the underlying inflammatory disease that lies at the core of HS, and that quelling the inflammation with adalimumab for at least 6 months before performing surgery with primary closure while the anti-TNF therapy continues would reduce the incidence of wound healing disorders.

This was borne out in the group’s small observational pilot study. It included 10 patients with HS who underwent surgery only after at least 6 months on adalimumab. Six had surgery for axillary HS and four for inguinal disease. Only 2 of the 10 developed a wound healing disorder. Both had surgical reconstruction in the inguinal area. Neither case involved infection. Surgical management entailed opening part of the suture to allow simultaneous secondary wound closure.

This 20% incidence of disordered wound healing when primary closure was carried out while systemic inflammation was controlled via adalimumab is markedly lower than rates reported using primary closure without adalimumab. Dr. Girbig and her coinvestigators are now conducting a larger controlled study to confirm their findings.

She reported having no financial conflicts regarding her study.

 

Delaying surgical reconstruction of fistula structures until after patients with hidradenitis suppurativa (HS) have been on adalimumab for a minimum of 6 months transforms primary wound closure into a highly attractive option, a pilot study suggests.

“Our experience suggests that under the effects of treatment with adalimumab, wound healing disorders with primary wound closure occur less often. And primary wound closure offers advantages over secondary wound healing: shorter length of inpatient stay, lower morbidity, fewer functional problems, and better quality of life,” Gefion Girbig, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

She noted that primary wound closure following surgery for HS is controversial. For example, current German guidelines recommend complete surgical excision of HS lesions, followed by secondary wound healing; the guidelines advise against primary wound closure. But those guidelines were issued back in 2012, years before adalimumab (Humira) achieved regulatory approval as the first and to date only medication indicated for treatment of HS.

Experts agree that while adalimumab has been a difference maker for many patients with HS, surgery is still often necessary. And many surgeons prefer secondary wound healing in HS. That’s because healing by first intention has historically often resulted in complications involving wound healing disorders and infection. These complications necessitate loosening of the primary closure to permit further wound healing by second intention, with a resultant prolonged healing time, explained Dr. Girbig, of the Institute for Health Sciences Research in Dermatology and Nursing at University Medical Center Hamburg-Eppendorf (Germany).



She and her coinvestigators hypothesized that the disordered wound healing is a consequence of the underlying inflammatory disease that lies at the core of HS, and that quelling the inflammation with adalimumab for at least 6 months before performing surgery with primary closure while the anti-TNF therapy continues would reduce the incidence of wound healing disorders.

This was borne out in the group’s small observational pilot study. It included 10 patients with HS who underwent surgery only after at least 6 months on adalimumab. Six had surgery for axillary HS and four for inguinal disease. Only 2 of the 10 developed a wound healing disorder. Both had surgical reconstruction in the inguinal area. Neither case involved infection. Surgical management entailed opening part of the suture to allow simultaneous secondary wound closure.

This 20% incidence of disordered wound healing when primary closure was carried out while systemic inflammation was controlled via adalimumab is markedly lower than rates reported using primary closure without adalimumab. Dr. Girbig and her coinvestigators are now conducting a larger controlled study to confirm their findings.

She reported having no financial conflicts regarding her study.

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Is There an Association Between Hidradenitis Suppurativa and Fibromyalgia?

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To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory condition that affects approximately 1% to 4% of the worldwide population and is 3 times more common in females than in males.1 The condition is characterized by painful inflamed nodules in apocrine gland–bearing regions that can progress to abscesses, sinus tracts, and/or scarring. Hidradenitis suppurativa is associated with intense pain, work disability, and poor quality of life.1

Recent evidence has suggested that HS is an autoimmune disease resulting from dysregulation of the γ-secretase/Notch pathway, leading to stimulation of the toll-like receptor–mediated innate immunity that contributes to occlusion and inflammation of the hair follicle. Additionally, elevated levels of proinflammatory cytokines such as tumor necrosis factor α and IL-17 are seen in HS lesions.2 The autoimmune nature of HS may account for its increased association with other autoimmune disorders such as thyroid disease and potentially with other unexplored conditions such as fibromyalgia.3

Fibromyalgia is a chronic pain condition that primarily affects females and is commonly associated with other autoimmune conditions.4 The primary objective of this retrospective study was to determine the prevalence of fibromyalgia in HS patients and assess if there is an association between HS disease severity and development of fibromyalgia.

We conducted a retrospective chart review of patients at Wake Forest Baptist Medical Center (Winston-Salem, North Carolina) who were 18 years and older and had a diagnosis of both HS and fibromyalgia from January 2008 to November 2018. The primary end point was the prevalence of fibromyalgia in the HS population. The secondary end point was the association of HS disease severity with the development of fibromyalgia. Hidradenitis disease severity was defined according to the number of body areas affected by HS: mild disease involved 1 body area, moderate disease involved 2 body areas, and severe disease involved 3 or more body areas. Patient age, sex, and race also were recorded.

A total of 1356 patients were seen during this time period for HS. The prevalence of fibromyalgia in the HS population was 3.2% (n=44). Ninety-five percent (42/44) of patients with HS and fibromyalgia were women; 22 (50%) patients had severe disease, 12 (27%) had moderate disease, 7 (16%) had mild disease, and 3 (7%) had an unknown number of affected body areas. Fifty-seven percent (25/44) of patients were diagnosed with HS prior to the diagnosis of fibromyalgia (Table).



In our study, the prevalence of fibromyalgia in HS patients was lower than the overall prevalence estimates of up to 6% in the United States.5 Although fibromyalgia is associated with other autoimmune conditions, it does not appear that fibromyalgia occurs more frequently in the HS population than the general population. A limitation of this study was that we only included academic outpatient clinic visits at one institution, which may not be representative of the entire HS population. Fibromyalgia was one of the many pain disorders in this population of patients. In this population of HS patients, many had pain issues with diagnoses ranging from chronic pain syndrome to osteoarthritis. Additionally, many patients could meet criteria for fibromyalgia but may not have been formally diagnosed, as it is a diagnosis of exclusion and there is no formal test for diagnosis. Further studies are recommended to evaluate the association between HS and fibromyalgia.

References
  1. Smith MK, Nichlson CL, Parks-Miller A, et al. Hidradenitis suppurativa: an update on connecting the tracts. F1000Res. 2017;6:1272.
  2. Napolitano M, Megna M, Timoshchuk EA, et al. Hidradenitis suppurativa: from pathogenesis to diagnosis and treatment. Clin Cosmet Investig Dermatol. 2017;10:105-115.
  3. Miller IM, Vinding G, Sorensen HA, et al. Thyroid function in hidradenitis suppurativa: a population-based cross-sectional study from Denmark. Clin Exp Dermatol. 2018;43:899-905.
  4. Giacomelli C, Talarico R, Bombardieri S, et al. The interaction between autoimmune diseases and fibromyalgia: risk, disease course and management. Expert Rev Clin Immunol. 2013;9:1069-1076.
  5. Queiroz LP. Worldwide epidemiology of fibromyalgia. Curr Pain Headache Rep. 2013;17:356.
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From the Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Ms. Kolli, Drs. Habet and Herrera, and Mr. Haidari report no conflict of interest. Dr. Pichardo has received consulting support from AbbVie.

Correspondence: Sree S. Kolli, BA, Department of Dermatology, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157-1071 ([email protected]).

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Ms. Kolli, Drs. Habet and Herrera, and Mr. Haidari report no conflict of interest. Dr. Pichardo has received consulting support from AbbVie.

Correspondence: Sree S. Kolli, BA, Department of Dermatology, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157-1071 ([email protected]).

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Ms. Kolli, Drs. Habet and Herrera, and Mr. Haidari report no conflict of interest. Dr. Pichardo has received consulting support from AbbVie.

Correspondence: Sree S. Kolli, BA, Department of Dermatology, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157-1071 ([email protected]).

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To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory condition that affects approximately 1% to 4% of the worldwide population and is 3 times more common in females than in males.1 The condition is characterized by painful inflamed nodules in apocrine gland–bearing regions that can progress to abscesses, sinus tracts, and/or scarring. Hidradenitis suppurativa is associated with intense pain, work disability, and poor quality of life.1

Recent evidence has suggested that HS is an autoimmune disease resulting from dysregulation of the γ-secretase/Notch pathway, leading to stimulation of the toll-like receptor–mediated innate immunity that contributes to occlusion and inflammation of the hair follicle. Additionally, elevated levels of proinflammatory cytokines such as tumor necrosis factor α and IL-17 are seen in HS lesions.2 The autoimmune nature of HS may account for its increased association with other autoimmune disorders such as thyroid disease and potentially with other unexplored conditions such as fibromyalgia.3

Fibromyalgia is a chronic pain condition that primarily affects females and is commonly associated with other autoimmune conditions.4 The primary objective of this retrospective study was to determine the prevalence of fibromyalgia in HS patients and assess if there is an association between HS disease severity and development of fibromyalgia.

We conducted a retrospective chart review of patients at Wake Forest Baptist Medical Center (Winston-Salem, North Carolina) who were 18 years and older and had a diagnosis of both HS and fibromyalgia from January 2008 to November 2018. The primary end point was the prevalence of fibromyalgia in the HS population. The secondary end point was the association of HS disease severity with the development of fibromyalgia. Hidradenitis disease severity was defined according to the number of body areas affected by HS: mild disease involved 1 body area, moderate disease involved 2 body areas, and severe disease involved 3 or more body areas. Patient age, sex, and race also were recorded.

A total of 1356 patients were seen during this time period for HS. The prevalence of fibromyalgia in the HS population was 3.2% (n=44). Ninety-five percent (42/44) of patients with HS and fibromyalgia were women; 22 (50%) patients had severe disease, 12 (27%) had moderate disease, 7 (16%) had mild disease, and 3 (7%) had an unknown number of affected body areas. Fifty-seven percent (25/44) of patients were diagnosed with HS prior to the diagnosis of fibromyalgia (Table).



In our study, the prevalence of fibromyalgia in HS patients was lower than the overall prevalence estimates of up to 6% in the United States.5 Although fibromyalgia is associated with other autoimmune conditions, it does not appear that fibromyalgia occurs more frequently in the HS population than the general population. A limitation of this study was that we only included academic outpatient clinic visits at one institution, which may not be representative of the entire HS population. Fibromyalgia was one of the many pain disorders in this population of patients. In this population of HS patients, many had pain issues with diagnoses ranging from chronic pain syndrome to osteoarthritis. Additionally, many patients could meet criteria for fibromyalgia but may not have been formally diagnosed, as it is a diagnosis of exclusion and there is no formal test for diagnosis. Further studies are recommended to evaluate the association between HS and fibromyalgia.

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory condition that affects approximately 1% to 4% of the worldwide population and is 3 times more common in females than in males.1 The condition is characterized by painful inflamed nodules in apocrine gland–bearing regions that can progress to abscesses, sinus tracts, and/or scarring. Hidradenitis suppurativa is associated with intense pain, work disability, and poor quality of life.1

Recent evidence has suggested that HS is an autoimmune disease resulting from dysregulation of the γ-secretase/Notch pathway, leading to stimulation of the toll-like receptor–mediated innate immunity that contributes to occlusion and inflammation of the hair follicle. Additionally, elevated levels of proinflammatory cytokines such as tumor necrosis factor α and IL-17 are seen in HS lesions.2 The autoimmune nature of HS may account for its increased association with other autoimmune disorders such as thyroid disease and potentially with other unexplored conditions such as fibromyalgia.3

Fibromyalgia is a chronic pain condition that primarily affects females and is commonly associated with other autoimmune conditions.4 The primary objective of this retrospective study was to determine the prevalence of fibromyalgia in HS patients and assess if there is an association between HS disease severity and development of fibromyalgia.

We conducted a retrospective chart review of patients at Wake Forest Baptist Medical Center (Winston-Salem, North Carolina) who were 18 years and older and had a diagnosis of both HS and fibromyalgia from January 2008 to November 2018. The primary end point was the prevalence of fibromyalgia in the HS population. The secondary end point was the association of HS disease severity with the development of fibromyalgia. Hidradenitis disease severity was defined according to the number of body areas affected by HS: mild disease involved 1 body area, moderate disease involved 2 body areas, and severe disease involved 3 or more body areas. Patient age, sex, and race also were recorded.

A total of 1356 patients were seen during this time period for HS. The prevalence of fibromyalgia in the HS population was 3.2% (n=44). Ninety-five percent (42/44) of patients with HS and fibromyalgia were women; 22 (50%) patients had severe disease, 12 (27%) had moderate disease, 7 (16%) had mild disease, and 3 (7%) had an unknown number of affected body areas. Fifty-seven percent (25/44) of patients were diagnosed with HS prior to the diagnosis of fibromyalgia (Table).



In our study, the prevalence of fibromyalgia in HS patients was lower than the overall prevalence estimates of up to 6% in the United States.5 Although fibromyalgia is associated with other autoimmune conditions, it does not appear that fibromyalgia occurs more frequently in the HS population than the general population. A limitation of this study was that we only included academic outpatient clinic visits at one institution, which may not be representative of the entire HS population. Fibromyalgia was one of the many pain disorders in this population of patients. In this population of HS patients, many had pain issues with diagnoses ranging from chronic pain syndrome to osteoarthritis. Additionally, many patients could meet criteria for fibromyalgia but may not have been formally diagnosed, as it is a diagnosis of exclusion and there is no formal test for diagnosis. Further studies are recommended to evaluate the association between HS and fibromyalgia.

References
  1. Smith MK, Nichlson CL, Parks-Miller A, et al. Hidradenitis suppurativa: an update on connecting the tracts. F1000Res. 2017;6:1272.
  2. Napolitano M, Megna M, Timoshchuk EA, et al. Hidradenitis suppurativa: from pathogenesis to diagnosis and treatment. Clin Cosmet Investig Dermatol. 2017;10:105-115.
  3. Miller IM, Vinding G, Sorensen HA, et al. Thyroid function in hidradenitis suppurativa: a population-based cross-sectional study from Denmark. Clin Exp Dermatol. 2018;43:899-905.
  4. Giacomelli C, Talarico R, Bombardieri S, et al. The interaction between autoimmune diseases and fibromyalgia: risk, disease course and management. Expert Rev Clin Immunol. 2013;9:1069-1076.
  5. Queiroz LP. Worldwide epidemiology of fibromyalgia. Curr Pain Headache Rep. 2013;17:356.
References
  1. Smith MK, Nichlson CL, Parks-Miller A, et al. Hidradenitis suppurativa: an update on connecting the tracts. F1000Res. 2017;6:1272.
  2. Napolitano M, Megna M, Timoshchuk EA, et al. Hidradenitis suppurativa: from pathogenesis to diagnosis and treatment. Clin Cosmet Investig Dermatol. 2017;10:105-115.
  3. Miller IM, Vinding G, Sorensen HA, et al. Thyroid function in hidradenitis suppurativa: a population-based cross-sectional study from Denmark. Clin Exp Dermatol. 2018;43:899-905.
  4. Giacomelli C, Talarico R, Bombardieri S, et al. The interaction between autoimmune diseases and fibromyalgia: risk, disease course and management. Expert Rev Clin Immunol. 2013;9:1069-1076.
  5. Queiroz LP. Worldwide epidemiology of fibromyalgia. Curr Pain Headache Rep. 2013;17:356.
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  • Although fibromyalgia does not occur more frequently in hidradenitis suppurativa (HS) patients, it is important to recognize that HS patients can have comorbidities that should be addressed when possible to improve overall quality of life.
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