Bhlish jounia! of Dcrnialoloim (I 991) 1 25. 384- JSh.
Hidradenitis suppurativa in Crohn's disease L.S.OSTLERK. I.A.A.LANGTKY. P.S.MOKTIMKK* AND K.C.D.STADGHTON l>par(mcins
of Oi-nmilolonLi. WestwinsUr
HospHiiI (uiil *.S'f Ceonie's Hospiliil. Loinlon
Accepted tor puhlicalion 1 7 May 1991
Summary
Three patients with Crohn's disease who developed the clinical features of hidradenitis suppurativa (HS) are reported. To our knowledge this assoeiation has not been previously described. These cases illustrate the similarity between cutaneous Crohn s and ano~genital HS once chronic and established.
Case reports Case 1
A 4f)-year old woman had a subtotal colectomy with ileostomy for Crohn's disease in 1 974. The rectum was left i>J situ in the hope of performing an ileorectal anastomosis at a later date. However, in view of continuing bloody discharge per rectum an abdominoperineal excision of the rectal stump was performed in ]97fi. Post operatively there was breakdown of the perineal wound with extensive local sepsis and perianai sinuses. This was initially thought to be perianai Crohn's disease, although multiple biopsies failed to support this diagnosis. A number of therapeutic measures were tried including multiple courses of antibiotics, photochemotherapy. azathioprine. quadruple anti-tuberculous therapy and several operations, but without success. The patient was referred to the dermatologists in 1987. There was no history of acne or axillary disease but she had noticed premenstrual flaring of the boils. On examination there was extensive intlammation in the ano-genital region with gross distorted swelling of the labia majora. Sinuses and abscesses extended over the mons pubis and into the perineum with multiple scars from previous surgery. There was a mild excess of body and facial hair. Investigations revealed a normal full blood count, glucose and hormone profile. Serum testosterone was 2 1 nmol/l (normal range ()-5-2-5). Skin swabs from the ano genital region grew Proteus, coliforms and coagulase-negative Stapluilocorcus durcus. A biopsy showed dermal scarring with marked acute and chronic intlammation. There were epithelialized sinus tracks with adjacent abscess formation. I here wore no granulomas. Treatment was commenced with clindamyfiu JOO Correspondence: Dr. L.S.Ostlere. IJc part me lit ol' Uerniatolot;y. The RoyaltreeHospital. Pond Street, Hampstead. London NVV3 IQG. U.K.
384
mg b.d. and prednisolone 10 mg al nighl to suppress adrenal androgens. There was a poor response and treatment was changed to Dianette, but again this had little impact. Finally, 15 tJy of radiotherapy was given over a lO-day course to the involved cutaneous areas using a 500 kV machine: this has proved to be the most effective treatment to date. The Crohn's disease has remained quiescent, with a functioning ileostomy. Case 2
A 5(i-year-old woman was diagnosed as having Crohn's disease in 1977. This was initially managed conservatively, but failure to respond to treatment required bowel resections in 198 3 and 1987. There was a history of recurrent boils in her groins which started around the same time as her bowel symptoms and she was referred to the dermatologists for this in 1986. On examination there was intlammation of the ano-genital region, with multiple abscesses and sinuses in the groins, extending over the mons pubis. with scarring and t)pen comedones {Fig. 1). The appearances were felt to be consistent with hidradenitis suppurativa (IIS} and tliis was supported by the histology, which showed no evidence of Crohn's disease. The patient underwent excision of the inguinal HS in 1989 and has since remained well.
Case J
A 48-year-old man was diagnosed as having Crohn's disease of the colon in 1 98 7. Treatment with sulphasalazine. high-dose prednisolone and azathioprine failed to control his symptoms and in May I 990 a panprocttK'olectomy was performed. One week after the operation, while on a reducing course of steroids, he developed an acutely painful rash in the groins which became so severe he was unable to walk. There was a possible history of boils in the groins in the past. On examination
HIDRADKNITIS SIIPI'UKATIVA IN CKOHNS DISHASK
I'igurf 1. Case 2; multiplL' ahstL'SM'Siind siiui.sfs in llic groins iiiui the mons pubi.s with sciirrinj' and opt-n uiriicdonos.
thtTc was swelling aiul erythema of llic groins, wilh multiple poinllng iibsccsses. These extended around the perineum and t)n to the buttoeks. A biopsy showed a demieil infliimmatory intiltrate and folliciilar plugging consistent with the diagnosis ot'HS. The close of prcdnisolone was increased from 1 to 30 mg and he was started on minocyeline and metronlda/ole. 'I'lu' rash greatly improved over the next 10 days, lie tht-ri developed urticaria which resolved witliin 24 h of stopping the antibiotics, Isolrelinoin was given in a dosage of 0-5 mg/kg and the steroids were tailed off. Alter 10 weeks the isotretinoin was stopped due to the development of lethargy and generalized aches and pains. There has been no relapse of the HS or Crohn's disease. I-^xamination of the groins has shown occasional nodules with minimal scarring and post-intlammatory hyperpigmentatlon.
Discussion Cutaneous manifestations of inflammatory bowel disease are well recognized. In a review of 700 patients wilh inflammatory bowel disease. lOS had skin nuinilestations.' The incidence of skin lesions was highest in patients with involvement of the colon and lowest in those with ileal disease. The commonest skin complications were erythema nodosum (4 3 of 700 patients) and pyoderma gangrenosum (If) of 700 patients). Others included urticaria, vitiligo. Stevens-Iohnson syndrome, psoriasis and lupus erythematosis. Perineal Crohn's disease is commtm. occurring in about 30% of patients," while nietastatic Crohn's disease, a granulomatons reaction of the skin that is non-contiguous to ihe gastrointestinal tract, is rare. Since its description hy
Parks i'( ((/. in IShS.' 24 cases have been reported.^ Many of the cases were initially misdiagnosed, partly dne to the variable morphology of the lesions.^ To our knowledge the association of hidradenitis suppurativa and Crohn's disease has not heen previously reported. The three patients presented all developed HS between I and 3 years after tlie bowel symptoms started. In Cases 2 and 3 inflammation was limited to the colon. Case 3 differed from tfie other two patients in the aciiteness of onset. He pr(jbably had mild HS which was precipitated by withdrawal of steroids. In all three patients the HS was limited to the perineal region and none of them had associated acne. The disease activity of the bowel and the hidradenitis did not appear to be related in any of the patients. The ahove three cases demonstrate that ano-genital sinuses and abscesses m;iy be due to HS and not cutaneous Crohn's disease, even if the patient has gastrointestinal Crohn's disease. Ant)-genital HS may only he distinguished from Crohn's diseiise from the history as the established forms may have similar histology and clinical appearance. A diagnosis of HS depends on the following features:'' onset at or after puberty: a poor response to conventional courses of antibiotics, with a tendency to early relapse: the presence of comedones: routine culture of pus revealing no pathogens and premenstrual exacerbations in women. The aetiology of both HS and Crohn's disease remains elusive. Although HS is ct)nsidered a disease of apocrine glands there is little evidence to support this and a more likely mechanism is follicular occlusion within apocrine gland-hearing skin.' The association with otiier conditions in which follicular occlusion is a prominent feature, namely acne conglobata. pilonidai sinus and dissecting cellulitis of the scalp, would tend to support this view. Hidradenitis suppurativa is only readily identifiable when in an established chronic form. Although there are no ligures on prevalence, the severe Ibrni is considered rare. However, recurrent apocrine boils of a type seen in early HS are not uncommon in the age group most subject to acne. This suggests that in some patients HS reaches a stage from which it becomes self-perpetuating and chronic. Crohn's disease is another condition characterized pathologically by squamous-cell-lined structures and abscesses. C3ranulomata, while a feature of Crohn's disease, can also he seen in HS owing to the distortion of follicles and phagocytosis of keratin. Thus it can be seen that HS and Crohn's disease have similarities and may easily he clinically confused in ano-genital sites. While the two conditions have different origins they may
386
L.S.OSTLERE et al
share a final common pathway once established and chronic. Autointoxication is the concept that diseases may result from absorption of toxins from the bowel, and is a possible explanation of the association between Crohn's disease and HS. Person and Bernhard*^ concluded that it could explain many bowel related sicin conditions including those associated with inflammatory bowel disease, small bowel bypass surgery, dermatitis herpetitbrmis and psoriasis. They proposed that even minor detects ol' gut mucosal barrier function may result in failure of gut IgA to inactivate bacterial or dietary antigens. The IgA immune complexes formed are deposited in the sicin. Cutaneous expression ol disease may be affected by host and microbial factors, as well as by immune complex size and concentration, Evidence lor this theory includes the presence of IgA immune complexes in dermatitis herpetiformis which increase after oral wheat challenge.'' In addition psoriasis is significantly more common in patients with inflammatory bowel disease'" and circulating IgA immune complexes have been found in 67% of patients with psoriasis compared with 4% of controls." possibly the result of subciinical bowel inflammation. In Crohn's disease much circumstantial evidence indicates the importance of immune mechanisms causing tissue injury.'' A number of causative organisms and environmental agents have been suggested, with no conclusive evidence.'' Some features such as erythema nodosum, pyoderma gangrenosum and leukocytoclastic vasculitis would be compatible with the deposition of immune complexes possibly formed from microbial antigens that have been absorbed through the damaged niucosa. Circulating immune complexes have been found, but these are not specific to inflammatory bowel disease.'" Although HS has not been previously described in inflammatory bowel disease, a case of Crohn's disease developing in a patient with acne fulminans has heen
reported.'"* Acne, classically the conglobata variety, commonly occurs in patients with HS and it is possible that similar mechanisms could be applied to this case. The clinical and histological features of established ano-genital HS and cutaneous Crohn's disease may be very similar, and the history is important in distinguishing the two conditions. While the two conditions may have different origins, once they become chronic similar pathological processes may exist.
References 1 Cireenstctn Al. [anowilz HI), Sachar 1)11, The exlrii-inlesLiniil complicalions of Crohn's dis{;ast' and ulccrativc colitis: A study of 700 patients. Medkinc iy7f); 55: 401-12. 2 HobbissIH, Scholield PF. Management of perianal Cmhn's disease, IRSoiMed 1982: 75:414-17, } Parks AG, Morson BC, Pegum |S, Crohn's disease with cutaneous involvemtmt. ?wc K Soc Med 19f>5: 58: 241-2. 4 Shuni I)T. Guenther L, Metastatic Crohn's disease'. Arvh Dennulol 1440: 126: M 5 - 8 , 5 Buckley C, Bayoumi AHM, Sarkiiny I. Metastatic Crohn's disease. Chn Hxp Dcrmaiol i940: 15: 1 J l - J . f) Mortimer P, Hidradenitis suppurativa—diagnostic criteria. In: Acne and Helated Disorders. Proceedings of an International Symposium, Cardiff 1988. (Marks R. Plewig C. eds), 1st cdn. London: Martin Uunit/. Ltd. 1989: i59-fiO. 7 Yu CC-W, Cook MG. Hidradenitis suppurativa: u disease of fbllicular cpilhelium, rather than apucrine glands. Hr / Dernmtol 1990: 122: 7(i J-9. K Person IR, Bernhard ID, Aut()intoxicati{)n revisited, / Am Aiiul Dcrmawl 198(1: 15: 559-63, 9 'Zone J[, I^Salle BA. Provost TV. Induction of IgA circulating immune complexes after wheat feedinj; in dermatitis herpetiformis patients. / lim'st Dcrmiilo! 1982; 78: i7S-80. 10 Yates VM, Watkinsori C. Kelman A, Further evidence for an association between psoriasis. Crohn's disease and ulcerative colitis, iir I !}fr>mitol 1982: 106: J 2 i - J 0 , I I Hall RP, Peck (11.. LawleyT|. Circulating IgA immune complexes in patients with psoriasis. / Invest Dcrmatol 198 i: 80: 4fiS-8. 12 Stniber W. lames SP, The immunobgic basis of inflammatory bowel disease, / CUn Immunol 1986: 6: 41 5-J2. 1 i Kirsner |B. The 'idiopathic' inflammatory bowel diseases. Their cause and pathogenesis. Arch Dermato! 1982: 118: 280-2. 14 McAuley D. Miller RA, Acne fulminans associated with inflammatory bowel disease. Arch Dermatol 1985: 121: 9 1 - i .
Hidradenitis suppurativa in Crohn's disease L.S.OSTLERK. I.A.A.LANGTKY. P.S.MOKTIMKK* AND K.C.D.STADGHTON l>par(mcins
of Oi-nmilolonLi. WestwinsUr
HospHiiI (uiil *.S'f Ceonie's Hospiliil. Loinlon
Accepted tor puhlicalion 1 7 May 1991
Summary
Three patients with Crohn's disease who developed the clinical features of hidradenitis suppurativa (HS) are reported. To our knowledge this assoeiation has not been previously described. These cases illustrate the similarity between cutaneous Crohn s and ano~genital HS once chronic and established.
Case reports Case 1
A 4f)-year old woman had a subtotal colectomy with ileostomy for Crohn's disease in 1 974. The rectum was left i>J situ in the hope of performing an ileorectal anastomosis at a later date. However, in view of continuing bloody discharge per rectum an abdominoperineal excision of the rectal stump was performed in ]97fi. Post operatively there was breakdown of the perineal wound with extensive local sepsis and perianai sinuses. This was initially thought to be perianai Crohn's disease, although multiple biopsies failed to support this diagnosis. A number of therapeutic measures were tried including multiple courses of antibiotics, photochemotherapy. azathioprine. quadruple anti-tuberculous therapy and several operations, but without success. The patient was referred to the dermatologists in 1987. There was no history of acne or axillary disease but she had noticed premenstrual flaring of the boils. On examination there was extensive intlammation in the ano-genital region with gross distorted swelling of the labia majora. Sinuses and abscesses extended over the mons pubis and into the perineum with multiple scars from previous surgery. There was a mild excess of body and facial hair. Investigations revealed a normal full blood count, glucose and hormone profile. Serum testosterone was 2 1 nmol/l (normal range ()-5-2-5). Skin swabs from the ano genital region grew Proteus, coliforms and coagulase-negative Stapluilocorcus durcus. A biopsy showed dermal scarring with marked acute and chronic intlammation. There were epithelialized sinus tracks with adjacent abscess formation. I here wore no granulomas. Treatment was commenced with clindamyfiu JOO Correspondence: Dr. L.S.Ostlere. IJc part me lit ol' Uerniatolot;y. The RoyaltreeHospital. Pond Street, Hampstead. London NVV3 IQG. U.K.
384
mg b.d. and prednisolone 10 mg al nighl to suppress adrenal androgens. There was a poor response and treatment was changed to Dianette, but again this had little impact. Finally, 15 tJy of radiotherapy was given over a lO-day course to the involved cutaneous areas using a 500 kV machine: this has proved to be the most effective treatment to date. The Crohn's disease has remained quiescent, with a functioning ileostomy. Case 2
A 5(i-year-old woman was diagnosed as having Crohn's disease in 1977. This was initially managed conservatively, but failure to respond to treatment required bowel resections in 198 3 and 1987. There was a history of recurrent boils in her groins which started around the same time as her bowel symptoms and she was referred to the dermatologists for this in 1986. On examination there was intlammation of the ano-genital region, with multiple abscesses and sinuses in the groins, extending over the mons pubis. with scarring and t)pen comedones {Fig. 1). The appearances were felt to be consistent with hidradenitis suppurativa (IIS} and tliis was supported by the histology, which showed no evidence of Crohn's disease. The patient underwent excision of the inguinal HS in 1989 and has since remained well.
Case J
A 48-year-old man was diagnosed as having Crohn's disease of the colon in 1 98 7. Treatment with sulphasalazine. high-dose prednisolone and azathioprine failed to control his symptoms and in May I 990 a panprocttK'olectomy was performed. One week after the operation, while on a reducing course of steroids, he developed an acutely painful rash in the groins which became so severe he was unable to walk. There was a possible history of boils in the groins in the past. On examination
HIDRADKNITIS SIIPI'UKATIVA IN CKOHNS DISHASK
I'igurf 1. Case 2; multiplL' ahstL'SM'Siind siiui.sfs in llic groins iiiui the mons pubi.s with sciirrinj' and opt-n uiriicdonos.
thtTc was swelling aiul erythema of llic groins, wilh multiple poinllng iibsccsses. These extended around the perineum and t)n to the buttoeks. A biopsy showed a demieil infliimmatory intiltrate and folliciilar plugging consistent with the diagnosis ot'HS. The close of prcdnisolone was increased from 1 to 30 mg and he was started on minocyeline and metronlda/ole. 'I'lu' rash greatly improved over the next 10 days, lie tht-ri developed urticaria which resolved witliin 24 h of stopping the antibiotics, Isolrelinoin was given in a dosage of 0-5 mg/kg and the steroids were tailed off. Alter 10 weeks the isotretinoin was stopped due to the development of lethargy and generalized aches and pains. There has been no relapse of the HS or Crohn's disease. I-^xamination of the groins has shown occasional nodules with minimal scarring and post-intlammatory hyperpigmentatlon.
Discussion Cutaneous manifestations of inflammatory bowel disease are well recognized. In a review of 700 patients wilh inflammatory bowel disease. lOS had skin nuinilestations.' The incidence of skin lesions was highest in patients with involvement of the colon and lowest in those with ileal disease. The commonest skin complications were erythema nodosum (4 3 of 700 patients) and pyoderma gangrenosum (If) of 700 patients). Others included urticaria, vitiligo. Stevens-Iohnson syndrome, psoriasis and lupus erythematosis. Perineal Crohn's disease is commtm. occurring in about 30% of patients," while nietastatic Crohn's disease, a granulomatons reaction of the skin that is non-contiguous to ihe gastrointestinal tract, is rare. Since its description hy
Parks i'( ((/. in IShS.' 24 cases have been reported.^ Many of the cases were initially misdiagnosed, partly dne to the variable morphology of the lesions.^ To our knowledge the association of hidradenitis suppurativa and Crohn's disease has not heen previously reported. The three patients presented all developed HS between I and 3 years after tlie bowel symptoms started. In Cases 2 and 3 inflammation was limited to the colon. Case 3 differed from tfie other two patients in the aciiteness of onset. He pr(jbably had mild HS which was precipitated by withdrawal of steroids. In all three patients the HS was limited to the perineal region and none of them had associated acne. The disease activity of the bowel and the hidradenitis did not appear to be related in any of the patients. The ahove three cases demonstrate that ano-genital sinuses and abscesses m;iy be due to HS and not cutaneous Crohn's disease, even if the patient has gastrointestinal Crohn's disease. Ant)-genital HS may only he distinguished from Crohn's diseiise from the history as the established forms may have similar histology and clinical appearance. A diagnosis of HS depends on the following features:'' onset at or after puberty: a poor response to conventional courses of antibiotics, with a tendency to early relapse: the presence of comedones: routine culture of pus revealing no pathogens and premenstrual exacerbations in women. The aetiology of both HS and Crohn's disease remains elusive. Although HS is ct)nsidered a disease of apocrine glands there is little evidence to support this and a more likely mechanism is follicular occlusion within apocrine gland-hearing skin.' The association with otiier conditions in which follicular occlusion is a prominent feature, namely acne conglobata. pilonidai sinus and dissecting cellulitis of the scalp, would tend to support this view. Hidradenitis suppurativa is only readily identifiable when in an established chronic form. Although there are no ligures on prevalence, the severe Ibrni is considered rare. However, recurrent apocrine boils of a type seen in early HS are not uncommon in the age group most subject to acne. This suggests that in some patients HS reaches a stage from which it becomes self-perpetuating and chronic. Crohn's disease is another condition characterized pathologically by squamous-cell-lined structures and abscesses. C3ranulomata, while a feature of Crohn's disease, can also he seen in HS owing to the distortion of follicles and phagocytosis of keratin. Thus it can be seen that HS and Crohn's disease have similarities and may easily he clinically confused in ano-genital sites. While the two conditions have different origins they may
386
L.S.OSTLERE et al
share a final common pathway once established and chronic. Autointoxication is the concept that diseases may result from absorption of toxins from the bowel, and is a possible explanation of the association between Crohn's disease and HS. Person and Bernhard*^ concluded that it could explain many bowel related sicin conditions including those associated with inflammatory bowel disease, small bowel bypass surgery, dermatitis herpetitbrmis and psoriasis. They proposed that even minor detects ol' gut mucosal barrier function may result in failure of gut IgA to inactivate bacterial or dietary antigens. The IgA immune complexes formed are deposited in the sicin. Cutaneous expression ol disease may be affected by host and microbial factors, as well as by immune complex size and concentration, Evidence lor this theory includes the presence of IgA immune complexes in dermatitis herpetiformis which increase after oral wheat challenge.'' In addition psoriasis is significantly more common in patients with inflammatory bowel disease'" and circulating IgA immune complexes have been found in 67% of patients with psoriasis compared with 4% of controls." possibly the result of subciinical bowel inflammation. In Crohn's disease much circumstantial evidence indicates the importance of immune mechanisms causing tissue injury.'' A number of causative organisms and environmental agents have been suggested, with no conclusive evidence.'' Some features such as erythema nodosum, pyoderma gangrenosum and leukocytoclastic vasculitis would be compatible with the deposition of immune complexes possibly formed from microbial antigens that have been absorbed through the damaged niucosa. Circulating immune complexes have been found, but these are not specific to inflammatory bowel disease.'" Although HS has not been previously described in inflammatory bowel disease, a case of Crohn's disease developing in a patient with acne fulminans has heen
reported.'"* Acne, classically the conglobata variety, commonly occurs in patients with HS and it is possible that similar mechanisms could be applied to this case. The clinical and histological features of established ano-genital HS and cutaneous Crohn's disease may be very similar, and the history is important in distinguishing the two conditions. While the two conditions may have different origins, once they become chronic similar pathological processes may exist.
References 1 Cireenstctn Al. [anowilz HI), Sachar 1)11, The exlrii-inlesLiniil complicalions of Crohn's dis{;ast' and ulccrativc colitis: A study of 700 patients. Medkinc iy7f); 55: 401-12. 2 HobbissIH, Scholield PF. Management of perianal Cmhn's disease, IRSoiMed 1982: 75:414-17, } Parks AG, Morson BC, Pegum |S, Crohn's disease with cutaneous involvemtmt. ?wc K Soc Med 19f>5: 58: 241-2. 4 Shuni I)T. Guenther L, Metastatic Crohn's disease'. Arvh Dennulol 1440: 126: M 5 - 8 , 5 Buckley C, Bayoumi AHM, Sarkiiny I. Metastatic Crohn's disease. Chn Hxp Dcrmaiol i940: 15: 1 J l - J . f) Mortimer P, Hidradenitis suppurativa—diagnostic criteria. In: Acne and Helated Disorders. Proceedings of an International Symposium, Cardiff 1988. (Marks R. Plewig C. eds), 1st cdn. London: Martin Uunit/. Ltd. 1989: i59-fiO. 7 Yu CC-W, Cook MG. Hidradenitis suppurativa: u disease of fbllicular cpilhelium, rather than apucrine glands. Hr / Dernmtol 1990: 122: 7(i J-9. K Person IR, Bernhard ID, Aut()intoxicati{)n revisited, / Am Aiiul Dcrmawl 198(1: 15: 559-63, 9 'Zone J[, I^Salle BA. Provost TV. Induction of IgA circulating immune complexes after wheat feedinj; in dermatitis herpetiformis patients. / lim'st Dcrmiilo! 1982; 78: i7S-80. 10 Yates VM, Watkinsori C. Kelman A, Further evidence for an association between psoriasis. Crohn's disease and ulcerative colitis, iir I !}fr>mitol 1982: 106: J 2 i - J 0 , I I Hall RP, Peck (11.. LawleyT|. Circulating IgA immune complexes in patients with psoriasis. / Invest Dcrmatol 198 i: 80: 4fiS-8. 12 Stniber W. lames SP, The immunobgic basis of inflammatory bowel disease, / CUn Immunol 1986: 6: 41 5-J2. 1 i Kirsner |B. The 'idiopathic' inflammatory bowel diseases. Their cause and pathogenesis. Arch Dermato! 1982: 118: 280-2. 14 McAuley D. Miller RA, Acne fulminans associated with inflammatory bowel disease. Arch Dermatol 1985: 121: 9 1 - i .
