CASE REPORT
Extragenital lichen sclerosus with aetiological link to Borrelia Lt Col Biju Vasudevan*, Lt Col Amitabh Sagar†, Lt Col Ashish Bahal#, Brig AP Mohanty, VSM** MJAFI 2011;67:370–373
INTRODUCTION
lesions elsewhere, photosensitivity, muscle weakness or weight loss. She gave history that 15 years back she had an episode of swelling of the right lower limb associated with solitary welldemarcated swelling in the right groin. The lesion regressed with antibiotics prescribed by a registered practitioner. The same swelling had recurred one and a half years back with a similar course. Presently she did not have such complaints. General and systemic examination did not reveal any abnormality. Dermatological examination showed multiple plaques in a generalised asymmetrical distribution, each with different characteristics: (a) solitary hyperpigmented hyperkeratotic plaque of size 7 × 4 cm2 with surrounding well-defined hypopigmented margins on the lower back (Figure 1A); (b) multiple welldefined hypopigmented plaques with central hyperpigmented open comedone-like lesions on the upper back (Figure 1B); (c) porcelain white coloured solitary plaque on the right buttock and similar plaques along striae on flanks (Figures 1C and D); (d) partially well-defined areas of altered pigmentation on the right breast and extensor aspect of both legs (Figures 2A and B); (e) solitary well-defined atrophic plaque on the right shoulder. There were no genital or oral lesions and no evidence of systemic lupus, dermatomyositis or malignancy. Investigations showed normal haematocrit and biochemical investigations. Peripheral blood smear showed no Sézary cells. Serum for T3, T4, TSH, antinuclear antibodies, venereal disease research laboratory (VDRL) test, and antibodies against human immunodeficiency virus (HIV) were negative. Ultrasound and computed tomography scan of the abdomen were normal. Skin biopsy revealed a thinned out epidermis with vacuolar degeneration of basilar keratinocytes (Figures 3A and B). There was no follicular plugging. The upper dermis showed the presence of homogenous oedematous eosinophilic collagen fibrils while the lower dermis had haphazardly arranged fibrils (Figure 3C). Perivascular inflammatory infiltrate was found in the mid dermis below the homogenous layer (Figure 3D). It was also found that older the lesion, thinner were the epidermis and homogenous collagenous layer with lesser inflammatory infiltrate (Figure 4). Thus a diagnosis of extragenital lichen sclerosus was arrived at. Antibody tests revealed raised IgG titres against Borrelia burgdorferi. The IgM titres were negative. Culture from the skin lesions was however negative for Borrelia. She was treated with a course of oral doxycycline 100 mg twice daily and topical emollients for a month. The cutaneous lesions regressed in six weeks time leaving behind atrophic patches. Follow-up IgG titres became negative after 16 weeks.
Lichen sclerosus more popularly known as lichen sclerosus et atrophicans (LSA) or Csillag’s disease is an idiopathic inflammatory dermatosis of unknown aetiology affecting women 10 times more commonly than men and usually seen over 50 years of age.1 It is clinically characterised by small, porcelain white, sclerotic lesions occurring mainly on genital areas. Extragenital involvement, though occurring additionally in a few cases rarely occurs in isolation. Genetic factors and autoimmunity have been described as possible aetiologies. Symptoms commonly described are itching, burning and bleeding though dyspareunia, dysuria, and urinary obstruction have been reported to be associated with the disease.2 Diagnosis is clinico-pathological. Symptomatic treatment with emollients, antihistaminics, and topical corticosteroid ointments form the mainstay of treatment. Classical cutaneous manifestations associated with Borrelia are borrelial lymphocytoma, acrodermatatitis chronica atrophicans, and erythema migrans, though morphea and similar other conditions have rarely been attributed to this bacteria.3 We herein present a case of extragenital lichen sclerosus with varied morphological features and probable aetiological link to Borrelia.
CASE REPORT This 58-year-old lady, resident of Bihar presented to the skin department with complaints of dark raised lesions on the body of one-year duration. Initially the patient had noticed a solitary white lesion on the lower back which later developed a blackish colour and progressively increased in size. She later developed similar lesions on the upper back, buttocks, breast, and lower limbs. Mild itching was present. There was no history of
*Graded Specialist (Dermatology), Command Hospital (SC), Pune – 40, † Associate Professor, Department of Medicine, AFMC, Pune – 40, #Graded Specialist (Microbiology), **Commandant, Military Hospital, Shillong. Correspondence: Lt Col Biju Vasudevan, Graded Specialist (Dermatology), Command Hospital (SC), Pune – 40. E-mail: [email protected] Received: 19.05.2010; Accepted: 08.04.2011 doi: 10.1016/S0377-1237(11)60089-0
MJAFI Vol 67 No 4
370
© 2011, AFMS
Extragenital Lichen Sclerosus With Aetiological Link to Borrelia
A
B
C
D
Figure 1 Various cutaneous morphological manifestations: (A) hyperpigmented hyperkeratotic plaque with surrounding well-defined hypopigmented margin, (B) well-defined hypopigmented plaque with central hyperpigmented open-comedone like lesion, (C) porcelain white plaque on right buttock, and (D) similar plaques along striae on flanks.
A
B
Figure 2 Partially well-defined areas of altered pigmentation on: (A) right breast, and (B) extensor aspect of legs.
with HLA A29, B44, DQ-7, 8, and 9.4 Autoantibodies to glycoprotein extracellular matrix protein 1 have been demonstrated in few cases.5 Csillag’s disease affects anogenital area in 85–98% cases, with additional extragenital lesions being reported in 15–20% of patients.6 Extragenital lesions alone occur in 2.5% and are found usually on the back and shoulders.7 They are generally
DISCUSSION Lichen sclerosus is an inflammatory disease with a worldwide prevalence of 0.03%. The underlying cause is unknown with genetic predisposition, trauma, infections, vaccinations, autoimmune, and hormonal factors being described as the most likely causes. Immunogenetic studies have demonstrated links MJAFI Vol 67 No 4
371
© 2011, AFMS
Vasudevan, et al
A
B
C
D
Figure 3 Histopathology of skin lesions on haematoxylin and eosin staining showing: (A) thinned out epidermis (10×), (B) vacuolar degeneration of basilar keratinocytes (40×), (C) upper dermis showing presence of homogenous oedematous eosinophilic collagen fibrils while the lower dermis has haphazardly arranged fibrils (40×), and (D) perivascular inflammatory infiltrate in the mid dermis (40×).
asymptomatic and less common presentations include involvement of the palms, soles, infraorbital and scrotal regions, appearance in acrochordons, and scarring alopecia.8 Our patient, in addition, also had a hyperkeratotic plaque on the back, porcelain plaques along striae on the buttocks, and dyspigmented lesions on the breast and legs. These lesions have rarely been described earlier in the literature. Investigations include skin biopsy, autoimmune workup and borrelial antibody titres. Histopathology of LSA is specific with thin epidermis, basal cell degeneration, upper dermal homogenisation of collagen, and mid-dermal chronic inflammatory infiltrate, all of which were present in our case. B. burgdorferi can be identified either by isolation or polymerase chain reaction (PCR), both of which are not always successful. Clinical diagnosis is still the best method of diagnosis and raised IgG or IgM titres helps in establishing the cause when the clinical picture is uncertain, as in our case. Recently, focus floating microscopy was found to successfully detect Borrelia in tissue specimens.9 Our case had raised antibody titres. However, immunohistochemistry or PCR could not be carried out due to lack of facilities. An earlier study revealed an overall seropositivity of 13% to Borrelia in a population of 500 people in the north-eastern region of India with Arunachal Pradesh having the highest seroprevalence rate of 17.8%.10 The seroprevalence MJAFI Vol 67 No 4
rates in the USA, Europe, Japan, China, and Malaysia have been reported to be 2–12%, 26%, 5–21%, 5.06–26.2%, and 4.1%, respectively. Csillag’s disease usually responds to potent topical steroids. Other therapies reported to be beneficial include topical testosterone, oestrogen, potassium paraamino benzoate, calcipotriol, tacrolimus, pimecrolimus, intralesional steroids, systemic corticosteroids, systemic retinoids, methotrexate, cyclosporine, sulphasalzine, penicillamine, photodynamic therapy, and surgery.11 Our patient responded to anti-borrelial antibiotics and topical emollients. Earlier studies have described resolution of lichen sclerosus lesions with antibiotics like cephalosporins and penicillin.12 Borrelia has been aetiologically linked in few case reports to morphea, linear scleroderma, atrophoderma of Pierini and Pasini, Parry-Romberg progressive facial hemiatrophy, and Shulman’s syndrome. There has been evidence attributing lichen sclerosus to B. burgdorferi infection in very few reports from around the world and we have not found any reports from India.13,14 Our patient had complaints in the past suggestive of borrelial involvement and was associated with raised borrelial antibody titres which regressed with treatment. This case has been presented because of the very unique morphological lesions in a case of solely extragenital lichen 372
© 2011, AFMS
Extragenital Lichen Sclerosus With Aetiological Link to Borrelia
A
B
C
D
Figure 4 Sequence of histopathological changes based on the ageing of lesions. Gradual reduction in homogenous collagen layer and inflammatory infiltrate can be appreciated.
sclerosus, which is not very frequently reported and probable aetiological link to borrelial infection, which is rarely reported.
6. 7.
CONFLICTS OF INTEREST
8.
None identified. 9.
REFERENCES 10. 1. 2. 3. 4.
5.
Helm KF, Gibson LE, Muller SA. Lichen sclerosus et atrophicus in children and young adults. Pediatr Dermatol 1991;8:97–101. Al-Khenaizan S, Almuneef M, Kentab O. Lichen sclerosus mistaken for child sexual abuse. Int J Dermatol 2005;44:317–320. Trevisan G, Rees D, Stinco G. Borrelia burgdorferi and localized scleroderma. Clin Dermatol 1994;12:475–479. Marren P, Yell J, Charnock FM, Bunce M, Welsh K, Wojnarowska F. The association between lichen sclerosus and antigens of the HLA system. Br J Dermatol 1995;132:197–203. Chan I, Oyama N, Neill SM, Wojnarowska F, Black MM, McGrath JA. Characterization of IgG autoantibodies to extracellular matrix protein 1 in lichen sclerosus. Clin Exp Dermatol 2004;29:499–504.
MJAFI Vol 67 No 4
11. 12. 13.
14.
373
Meffert JJ, Davis BM, Grimwood RE. Lichen sclerosus. J Am Acad Dermatol 1995;32:393–416. Tremaine RDL, Miller RAW. Lichen sclerosus et atrophicus. Int J Dermatol 1989;28:10–16. Weigand DA. Microscopic features of lichen sclerosus et atrophicus in acrochordons: a clue to the cause of lichen sclerosus et atrophicus? J Am Acad Dermatol 1993;28:751–754. Eisendle K, Grabner T, Kutzner H, Zelger B. Possible role of Borrelia burgdorferi sensu lato infection in lichen sclerosus. Arch Dermatol 2008;144:662–663. Praharaj AK, Jetley S, Kalghatgi AT. Seroprevalence of Borrelia burgdorferi in North Eastern India. MJAFI 2008;64:26–28. Fischer G, Rogers M. Treatment of childhood vulvar lichen sclerosus with potent topical corticosteroid. Pediatr Dermatol 1997;14:235–238. Shelley WB, Shelley ED, Amurao CV. Treatment of lichen sclerosus with antibiotics. Int J Dermatol 2006;45:1104–1106. Schempp C, Bocklage H, Lange R, Kölmel HW, Orfanos CE, Gollnick H. Further evidence for Borrelia burgdorferi infection in morphea and lichen sclerosus et atrophicus confirmed by DNA amplification. J Investig Dermatol 1993;100:717–720. De Vito JR, Merogi AJ, Vo T, et al. Role of Borrelia burgdorferi in the pathogenesis of morphea/scleroderma and lichen sclerosus et atrophicus: a PCR study of thirty-five cases. J Cutan Pathol 1996;23:350–358.
© 2011, AFMS
Extragenital lichen sclerosus with aetiological link to Borrelia Lt Col Biju Vasudevan*, Lt Col Amitabh Sagar†, Lt Col Ashish Bahal#, Brig AP Mohanty, VSM** MJAFI 2011;67:370–373
INTRODUCTION
lesions elsewhere, photosensitivity, muscle weakness or weight loss. She gave history that 15 years back she had an episode of swelling of the right lower limb associated with solitary welldemarcated swelling in the right groin. The lesion regressed with antibiotics prescribed by a registered practitioner. The same swelling had recurred one and a half years back with a similar course. Presently she did not have such complaints. General and systemic examination did not reveal any abnormality. Dermatological examination showed multiple plaques in a generalised asymmetrical distribution, each with different characteristics: (a) solitary hyperpigmented hyperkeratotic plaque of size 7 × 4 cm2 with surrounding well-defined hypopigmented margins on the lower back (Figure 1A); (b) multiple welldefined hypopigmented plaques with central hyperpigmented open comedone-like lesions on the upper back (Figure 1B); (c) porcelain white coloured solitary plaque on the right buttock and similar plaques along striae on flanks (Figures 1C and D); (d) partially well-defined areas of altered pigmentation on the right breast and extensor aspect of both legs (Figures 2A and B); (e) solitary well-defined atrophic plaque on the right shoulder. There were no genital or oral lesions and no evidence of systemic lupus, dermatomyositis or malignancy. Investigations showed normal haematocrit and biochemical investigations. Peripheral blood smear showed no Sézary cells. Serum for T3, T4, TSH, antinuclear antibodies, venereal disease research laboratory (VDRL) test, and antibodies against human immunodeficiency virus (HIV) were negative. Ultrasound and computed tomography scan of the abdomen were normal. Skin biopsy revealed a thinned out epidermis with vacuolar degeneration of basilar keratinocytes (Figures 3A and B). There was no follicular plugging. The upper dermis showed the presence of homogenous oedematous eosinophilic collagen fibrils while the lower dermis had haphazardly arranged fibrils (Figure 3C). Perivascular inflammatory infiltrate was found in the mid dermis below the homogenous layer (Figure 3D). It was also found that older the lesion, thinner were the epidermis and homogenous collagenous layer with lesser inflammatory infiltrate (Figure 4). Thus a diagnosis of extragenital lichen sclerosus was arrived at. Antibody tests revealed raised IgG titres against Borrelia burgdorferi. The IgM titres were negative. Culture from the skin lesions was however negative for Borrelia. She was treated with a course of oral doxycycline 100 mg twice daily and topical emollients for a month. The cutaneous lesions regressed in six weeks time leaving behind atrophic patches. Follow-up IgG titres became negative after 16 weeks.
Lichen sclerosus more popularly known as lichen sclerosus et atrophicans (LSA) or Csillag’s disease is an idiopathic inflammatory dermatosis of unknown aetiology affecting women 10 times more commonly than men and usually seen over 50 years of age.1 It is clinically characterised by small, porcelain white, sclerotic lesions occurring mainly on genital areas. Extragenital involvement, though occurring additionally in a few cases rarely occurs in isolation. Genetic factors and autoimmunity have been described as possible aetiologies. Symptoms commonly described are itching, burning and bleeding though dyspareunia, dysuria, and urinary obstruction have been reported to be associated with the disease.2 Diagnosis is clinico-pathological. Symptomatic treatment with emollients, antihistaminics, and topical corticosteroid ointments form the mainstay of treatment. Classical cutaneous manifestations associated with Borrelia are borrelial lymphocytoma, acrodermatatitis chronica atrophicans, and erythema migrans, though morphea and similar other conditions have rarely been attributed to this bacteria.3 We herein present a case of extragenital lichen sclerosus with varied morphological features and probable aetiological link to Borrelia.
CASE REPORT This 58-year-old lady, resident of Bihar presented to the skin department with complaints of dark raised lesions on the body of one-year duration. Initially the patient had noticed a solitary white lesion on the lower back which later developed a blackish colour and progressively increased in size. She later developed similar lesions on the upper back, buttocks, breast, and lower limbs. Mild itching was present. There was no history of
*Graded Specialist (Dermatology), Command Hospital (SC), Pune – 40, † Associate Professor, Department of Medicine, AFMC, Pune – 40, #Graded Specialist (Microbiology), **Commandant, Military Hospital, Shillong. Correspondence: Lt Col Biju Vasudevan, Graded Specialist (Dermatology), Command Hospital (SC), Pune – 40. E-mail: [email protected] Received: 19.05.2010; Accepted: 08.04.2011 doi: 10.1016/S0377-1237(11)60089-0
MJAFI Vol 67 No 4
370
© 2011, AFMS
Extragenital Lichen Sclerosus With Aetiological Link to Borrelia
A
B
C
D
Figure 1 Various cutaneous morphological manifestations: (A) hyperpigmented hyperkeratotic plaque with surrounding well-defined hypopigmented margin, (B) well-defined hypopigmented plaque with central hyperpigmented open-comedone like lesion, (C) porcelain white plaque on right buttock, and (D) similar plaques along striae on flanks.
A
B
Figure 2 Partially well-defined areas of altered pigmentation on: (A) right breast, and (B) extensor aspect of legs.
with HLA A29, B44, DQ-7, 8, and 9.4 Autoantibodies to glycoprotein extracellular matrix protein 1 have been demonstrated in few cases.5 Csillag’s disease affects anogenital area in 85–98% cases, with additional extragenital lesions being reported in 15–20% of patients.6 Extragenital lesions alone occur in 2.5% and are found usually on the back and shoulders.7 They are generally
DISCUSSION Lichen sclerosus is an inflammatory disease with a worldwide prevalence of 0.03%. The underlying cause is unknown with genetic predisposition, trauma, infections, vaccinations, autoimmune, and hormonal factors being described as the most likely causes. Immunogenetic studies have demonstrated links MJAFI Vol 67 No 4
371
© 2011, AFMS
Vasudevan, et al
A
B
C
D
Figure 3 Histopathology of skin lesions on haematoxylin and eosin staining showing: (A) thinned out epidermis (10×), (B) vacuolar degeneration of basilar keratinocytes (40×), (C) upper dermis showing presence of homogenous oedematous eosinophilic collagen fibrils while the lower dermis has haphazardly arranged fibrils (40×), and (D) perivascular inflammatory infiltrate in the mid dermis (40×).
asymptomatic and less common presentations include involvement of the palms, soles, infraorbital and scrotal regions, appearance in acrochordons, and scarring alopecia.8 Our patient, in addition, also had a hyperkeratotic plaque on the back, porcelain plaques along striae on the buttocks, and dyspigmented lesions on the breast and legs. These lesions have rarely been described earlier in the literature. Investigations include skin biopsy, autoimmune workup and borrelial antibody titres. Histopathology of LSA is specific with thin epidermis, basal cell degeneration, upper dermal homogenisation of collagen, and mid-dermal chronic inflammatory infiltrate, all of which were present in our case. B. burgdorferi can be identified either by isolation or polymerase chain reaction (PCR), both of which are not always successful. Clinical diagnosis is still the best method of diagnosis and raised IgG or IgM titres helps in establishing the cause when the clinical picture is uncertain, as in our case. Recently, focus floating microscopy was found to successfully detect Borrelia in tissue specimens.9 Our case had raised antibody titres. However, immunohistochemistry or PCR could not be carried out due to lack of facilities. An earlier study revealed an overall seropositivity of 13% to Borrelia in a population of 500 people in the north-eastern region of India with Arunachal Pradesh having the highest seroprevalence rate of 17.8%.10 The seroprevalence MJAFI Vol 67 No 4
rates in the USA, Europe, Japan, China, and Malaysia have been reported to be 2–12%, 26%, 5–21%, 5.06–26.2%, and 4.1%, respectively. Csillag’s disease usually responds to potent topical steroids. Other therapies reported to be beneficial include topical testosterone, oestrogen, potassium paraamino benzoate, calcipotriol, tacrolimus, pimecrolimus, intralesional steroids, systemic corticosteroids, systemic retinoids, methotrexate, cyclosporine, sulphasalzine, penicillamine, photodynamic therapy, and surgery.11 Our patient responded to anti-borrelial antibiotics and topical emollients. Earlier studies have described resolution of lichen sclerosus lesions with antibiotics like cephalosporins and penicillin.12 Borrelia has been aetiologically linked in few case reports to morphea, linear scleroderma, atrophoderma of Pierini and Pasini, Parry-Romberg progressive facial hemiatrophy, and Shulman’s syndrome. There has been evidence attributing lichen sclerosus to B. burgdorferi infection in very few reports from around the world and we have not found any reports from India.13,14 Our patient had complaints in the past suggestive of borrelial involvement and was associated with raised borrelial antibody titres which regressed with treatment. This case has been presented because of the very unique morphological lesions in a case of solely extragenital lichen 372
© 2011, AFMS
Extragenital Lichen Sclerosus With Aetiological Link to Borrelia
A
B
C
D
Figure 4 Sequence of histopathological changes based on the ageing of lesions. Gradual reduction in homogenous collagen layer and inflammatory infiltrate can be appreciated.
sclerosus, which is not very frequently reported and probable aetiological link to borrelial infection, which is rarely reported.
6. 7.
CONFLICTS OF INTEREST
8.
None identified. 9.
REFERENCES 10. 1. 2. 3. 4.
5.
Helm KF, Gibson LE, Muller SA. Lichen sclerosus et atrophicus in children and young adults. Pediatr Dermatol 1991;8:97–101. Al-Khenaizan S, Almuneef M, Kentab O. Lichen sclerosus mistaken for child sexual abuse. Int J Dermatol 2005;44:317–320. Trevisan G, Rees D, Stinco G. Borrelia burgdorferi and localized scleroderma. Clin Dermatol 1994;12:475–479. Marren P, Yell J, Charnock FM, Bunce M, Welsh K, Wojnarowska F. The association between lichen sclerosus and antigens of the HLA system. Br J Dermatol 1995;132:197–203. Chan I, Oyama N, Neill SM, Wojnarowska F, Black MM, McGrath JA. Characterization of IgG autoantibodies to extracellular matrix protein 1 in lichen sclerosus. Clin Exp Dermatol 2004;29:499–504.
MJAFI Vol 67 No 4
11. 12. 13.
14.
373
Meffert JJ, Davis BM, Grimwood RE. Lichen sclerosus. J Am Acad Dermatol 1995;32:393–416. Tremaine RDL, Miller RAW. Lichen sclerosus et atrophicus. Int J Dermatol 1989;28:10–16. Weigand DA. Microscopic features of lichen sclerosus et atrophicus in acrochordons: a clue to the cause of lichen sclerosus et atrophicus? J Am Acad Dermatol 1993;28:751–754. Eisendle K, Grabner T, Kutzner H, Zelger B. Possible role of Borrelia burgdorferi sensu lato infection in lichen sclerosus. Arch Dermatol 2008;144:662–663. Praharaj AK, Jetley S, Kalghatgi AT. Seroprevalence of Borrelia burgdorferi in North Eastern India. MJAFI 2008;64:26–28. Fischer G, Rogers M. Treatment of childhood vulvar lichen sclerosus with potent topical corticosteroid. Pediatr Dermatol 1997;14:235–238. Shelley WB, Shelley ED, Amurao CV. Treatment of lichen sclerosus with antibiotics. Int J Dermatol 2006;45:1104–1106. Schempp C, Bocklage H, Lange R, Kölmel HW, Orfanos CE, Gollnick H. Further evidence for Borrelia burgdorferi infection in morphea and lichen sclerosus et atrophicus confirmed by DNA amplification. J Investig Dermatol 1993;100:717–720. De Vito JR, Merogi AJ, Vo T, et al. Role of Borrelia burgdorferi in the pathogenesis of morphea/scleroderma and lichen sclerosus et atrophicus: a PCR study of thirty-five cases. J Cutan Pathol 1996;23:350–358.
© 2011, AFMS
