Joint Dermatology Gynaecology Study Day University College Cork 

Saturday 7th November 2015

Langerhans cell histiocytosis presents as vulval disease in a 16-year-old female

E Nic Dhonncha¹, J Clowry¹, B Hennessy², J Stratton³, S Field¹

Dept of Dermatology¹, Dept of Haematology², Dept of Obstetrics and Gynaecology³, University Hospital Waterford

A healthy 16-year-old female presented to our gynaecology service with a 10 month history of progressively severe vulval irritation and pain. Examination under general anaesthetic revealed diffuse erythema, scattered erosions, superficial ulceration, and thickened mucosal surface of the labia majora and labia minora. Full skin and nail examination was otherwise normal.

Vulval biopsy showed extensively ulcerated skin, sheets of macrophages with grooved nuclei and eosinophils. Immunohistochemistry showed S100 and CD1a positivity confirming Langerhans Cell Histiocytosis (LCH).

Further clinical history revealed polyuria, polydipsia, and amenorrhea. Investigations revealed urine osmolality of 90mOsm/kg and serum osmolality of 307mOsm/kg consistent with Diabetes Insipidus. Low oestrogen, FSH, and LH levels, and MRI pituitary were consistent with involvement of the pituitary gland with LCH.

Topical barrier ointments and clobetasol propionate improved vulval symptoms. Following multidisciplinary assessment, our patient was started on systemic chemotherapy (Cytarabine) for multisystem-LCH without risk organ involvement.

 

LCH, previously known as “Histiocytosis X,” is a rare disease characterised by clonal proliferation of Langerhan-type cells. LCH mainly affects children, and is estimated to occur in 1-2 per million adults.  Vulval presentation of LCH occurs even less frequently with less than 30 cases of pure vulval LCH reported, which can present with pruritis, pain, dyspareunia, burning, discharge, presence of a discrete lesion or generalised ulceration.

Aetiology of LCH is unknown, and pathogenesis remains elusive. Diagnosis is challenging with clinical presentation varying depending on the organs affected which most commonly are the skin, bones, and pituitary gland. Diagnosis is clinicopathologic, and immunohistochemical staining with CD1a and, or CD207 has superseded electron microscopy. Recommended baseline investigations to assess disease extent include haematological, biochemical and coagulation studies, thyroid function tests, abdominal ultrasound, and skeletal survey.

 

Allergic Contact Dermatitis of the Vulva

Susan M. O’Gorman, MB, BCh Rochelle R. Torgerson, MD, PhD

Background and Objectives: Allergic contact dermatitis (ACD) of the vulva arises as a primary condition or develops secondary to topical agents. We aimed to describe the incidence of ACD in patients presenting with vulvar symptoms and to identify the allergens of most importance.

Patients and Methods: Using a database of the patch testing results from 3 geographically distinct sites, we identified patients tested to a gynecologic series between 2003 and 2010. Patients had patch testing to the standard European battery and a gynecologic series. Patch testing was in line with accepted universal methods: application on day 1, allergen removal and initial reading on day 3, and final reading on day 5.

Results: Ninety patients were included. Thirty-five (39%) had a relevant positive result. The 5 allergens with the highest number of cases with a relevant reaction were natural fragrance mix 2%, balsam of Peru, benzocaine 5%, fragrance mix 8%, and quaternium 15 1%. The most common gynecologic series allergen to cause a relevant reaction was terconazole.

Conclusions: ACD is a frequent finding in patients presenting with vulvar symptoms. We identified a relevant positive result to patch testing in 39%. We found fragrances, medicaments, and preservatives to be of most relevance.

 

Patch Testing in Female Genital Dermatoses

Foley CC, White S, Merry S, Nolan U, Collins P, Kirby B, Lally A

Department of Dermatology, St. Vincent’s University Hospital, Elm Park, Dublin 4

Genital dermatoses can be challenging for patients and dermatologists. Many patients are exposed to contact allergens from cleansing products and over the counter topical treatments prior to consulting a dermatologist. Patch testing may therefore be a useful investigation in this group of patients. The aim of this study was to identify the common allergens detected on patch testing in this group.

Patients with genital symptoms who underwent patch testing between January 2013 and October 2015 were reviewed (n=40, all female). There were 25 patients with vulval dermatitis, 12 with vulval pruritis and 3 patients with vulvodynia included in the study, ranging in age from 24 to 85 years (mean 45 years, median 40 years). The mean duration of symptoms prior to patch testing was 4.5 years (median 2 years, range 0-35 years).

The series tested included the BSCA standard series in all 40 patients, cosmetic/facial series in 17, medicament series in 25, fragrances/essential oils series in 31, textiles/colours/finishes series in 16, corticosteroid series in 5, caine mix breakdown in 5 and own products in 6 patients.

Allergic reaction to allergens was identified in 30/40 patients (75%) with 11/30 (37%) considered relevant to the presenting complaint, 8/30 (26%) of uncertain relevance and 11/30 (37%) of past relevance, e.g. nickel allergy. 16/40 reported an improvement in symptoms at time of patch testing, i.e. following advice from initial consultation. Of the 26 who attended follow-up post patch tesing, a further 5 reported improvement following patch testing and 5 reported no change in symptoms. Of the 11 patients with currently relevant contact allergens 7 had vulval dermatitis, 3 had vulval pruritis and 1 had vulvodynia as the presenting complaint.  Concurrent perianal symtpoms were present in 18/40 (45%) (7 vulval dermatitis, 8 vulval pruritis and 3 vulvodynia), of which 7/18 (39%) had ≥1 currently relevant allergens identified on patch testing.

The most common currently relevant contact allergens in this cohort were Balsam of Peru (5/11), caine mix III (4/11), with allergic reaction to dibucaine hydrochloride in 2/4, and fragrance mix I (4/11) suggesting that patients are using products in the genital area for  symptoms from another genital dermatosis (pruritis or eczema) prior to the development of genital allergic contact dermatitis.

This study re-emphasises the importance of skin care advice and avoidance of known allergens and irritants in the management of genital dermatoses.

 

 

Mucous Membrane Pemphigoid with treatment resistant oral and non scarring anogenital mucosal involvement

Nestor, L; Lally, A

A 60 year old lady presented to dermatology in 2008 with a three week history of an itchy blistering rash affecting her lower limbs. In addition she had vulval and mouth soreness and gritty eyes. She had a background history of Ulcerative Colitis diagnosed in 2002, treated initially with Azathioprine and Ciclosporin prior to proctocolectomy and ileal pouch formation in 2005. Histology from an intact blister showed subepidermal bullous formation with a predominant neutrophilic infiltrate. Direct immunofluorescence demonstrated linear deposition of IgA along the basement membrane zone. Serum sample sent for indirect immunofluorescence revealed epidermal binding IgA anti basement membrane zone antibodies. These results all supported the clinical diagnosis of Linear IgA disease.  The cutaneous component subsequently responded to dapsone however the mucosal involvement persisted and following this, a diagnosis of mucous membrane pemphigoid was made. Current treatment includes Dapsone 100mg once daily since 2008, Mycophenalate Mofetil 1g twice daily since 2011, and reducing dose oral steroids. Previous treatment included Lymecycline (x 1 year) Rituximab(x2 infusions),IVIG (x 6 months), Etanercept (x 3 months), Infliximab (x 6 months),Methotrexate(x 3 months), pulsed Methylprednisolone and throughout oral corticosteroids at doses of greater than 1mg/kg/day. More recently she received a trial of Thalidomide which she unfortunately failed to tolerate. Multidisciplinary management of this patient continues from dermatology to oral medicine, ophthalmology, haematology, gastroenterology and dietetics. She has declined treatment with Plasmapharesis/Cyclophosphamide to date.

Mucous Membrane Pemphigoid is a rare, chronic autoimmune blistering disorder characterised by subepithelial bullae and scarring with predominant mucosal involvement. Our case describes an unusual form, with non scarring anogenital involvement. It highlights also the recalcitrant nature of this condition. Early recognition of MMP may decrease disease related complications. However the diagnosis of MMP remains a challenge as patients may present to a variety of specialists and often with diverse clinical manifestations, highlighting the importance of multidisciplinary awareness and management.

 

  

Lichen sclerosus et atrophicus in monozygotic twins: a familial LS.

Fahy, CMR, Fitzgibbon J, Murphy M.

Lichen sclerosus (LS) is a chronic inflammatory skin disorder.  Although aetiology remains unclear, a genetic association is suggested.  We report the development of LS in monozygotic adult twins.

A 29 year old female was referred with a 5 year history of steroid – responsive vulval pruritus.  Symptoms were intermittent but flares were very disabling.  Clinical examination demonstrated typical features of LS.  Histopathology from biopsy was consistent with LS.  There was a good clinical response to appropriate use and duration of clobetasol ointment.  Her twin sister gave a history of  vulval irritation for some years.  Like her sister, there was no history of atopy, psoriasis or thyroid disease.  Overall, the clinical impression was also that of LS, not as severe as her sister’s but treatment also gave a rapid response.

There is a bimodal peak in LS in females, although our patients’ age is not typical.  Three pairs of female monozygotic twins (2 – 16 years) were reported with LS.  Monozygotic male twins, aged 9, were diagnosed with balanitis xerotica obliterans.  Familial LS had only been described in 37 families until the observational cohort study from 95 families attending the Oxford paediatric vulval clinic with a diagnosis of LS.  A positive family history of probable LS was found in 12% of women.

We report the development of LS in twins.  This is in line with literature supporting the hypothesis of a genetic aetiology with LS.  It is important to consider and identify LS in female patients of all ages as it may be under – recognised in pre – menopausal women.  This report suggests that with appropriate treatment, pre – menopausal women may respond faster and better than post – menopausal women.  The importance of history – taking is highlighted when reviewing patients with vulval signs and symptoms

 

 

Title: Intractable erosive lichen planus treated successfully with rituximab

Authors: Kara Heelan¹, Catherine Quinlan¹ , Maeve A McAleer¹, Christine McCreary², Michelle Murphy¹

Affiliations: ¹ Department of Dermatology, South Infirmary-Victoria University Hospital, Cork, Ireland

² Cork University Dental School and Hospital, Wilton, Cork, Ireland

Erosive lichen planus (LP) is a chronic recurrent disease that manifests as oral erosive ulcers affecting oral and genital mucosa.¹ More rarely it can affect esophageal, lacrimal, conjunctival and laryngeal mucosa. Erosive LP is very difficult to treat. Potent topical corticosteroids, systemic corticosteroids, immunosuppressant’s and retinoids are often used but rarely effective in recalcitrant disease.  More recently biologic agents including etanercept, adalimumab, infliximab, efalizumab, basiliximab and alefacept have been used with some success.² We report two cases of vulvo-vaginal gingival LP who achieved disease remission with rituximab.

References

1. Crincoli V, Di Bisceglie MB, Scivetti M, Lucchese A, Tecco S, Festa F. Oral lichen planus: update on etiopathogenesis, diagnosis and treatment. Immunopharmacology and immunotoxicology 2011;33:11-20.
2. O’Neill ID, Scully C. Biologics in oral medicine: ulcerative disorders. Oral Dis 2013;19:37-45.

 

 

Enhanced expression of IL-17, IL-10 and IL-1β in Hidradenitis suppurativa.

G Kelly¹, CM Sweeney¹, Hughes R¹, van den Born M¹, R Fitzgerald², A Lally¹, AM Tobin², B Kirby¹.

¹Dermatology Research Group, St. Vincent’s Hospital, Dublin 4. ²Adelaide and Meath Hospital, Tallaght, Dublin 24.

Background: Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory disease of follicular occlusion characterised by recurrent painful boils, sinus tracts, fistulae and scarring. The prevalence of HS is estimated at 1-4% of the population. The exact aetiology of HS is unknown but recent evidence suggests that immune dysregulation plays a role in disease initiation and progression.¹ This is further supported by the presence of immune cells and their products in HS lesions, an association with other immune-mediated diseases and the encouraging use of TNF-α inhibitors in this disease.

Objectives: We examined the expression of cytokines and inflammatory markers in the peripheral blood and skin of HS patients.

Methods: Serum, peripheral blood mononuclear cells [PBMC] and skin were obtained from 30 HS patients [age 24-64 years, M:F 9:21, Hurley stage I/II/III] and from healthy controls. The expression of pro-inflammatory and anti-inflammatory cytokines was determined by ELISA, flow cytometry and confirmed by RT-PCR.

Results: The expression of several inflammatory cytokines, including IL-17 and Th17 associated cytokines, is enhanced in HS skin and in the peripheral blood. The expression of highly sensitive C-reactive protein and IL-10 is enhanced in HS serum indicating significant systemic inflammation (p<0.05). The production of IL-17 and IL-10 by PBMC from HS patients in response to CD3 and CD28 activation was enhanced (P<0.05). CD45+ cells infiltrate the skin of HS patients and produce IL-17. Further characterisation of these cells revealed that CD3+ T cells and HLA-DR+ antigen presenting cells produced IL-17 in HS skin. CD1a+ dendritic cells produce IL-1β in HS skin. mRNA expression of the inflammasome associated cytokines IL-1β and IL-18 along with NLRP-3 was significantly enhanced in both perilesional and lesional skin from HS patients. These novel findings in a large group of hidradenitis patients suggest that immune pathways are involved in HS pathogenesis supporting the hypothesis that immune dysregulation is important in HS.

Conclusion:

Therapies targeting IL-1β and IL-17 pathways may represent novel therapeutic options for this debilitating disease.

1. van der Zee HH, Laman JD, Boer J, Prens EP. Hidradenitis suppurativa: viewpoint on clinical phenotyping, pathogenesis and novel treatments. Exp Dermatol.2012;21:735-9.

This study was supported by a research grant from Abbvie.

 

A case of genital pyoderma gangrenosum successfully treated with ciclosporin without relapse of established follicular lymphoma and a review of relevant existing literature

L Roche, C Gulman, M O’Kane, Connolly Hospital/Beaumont Hospital, Dublin

Pyoderma gangrenosum (PG) is an ulcerating neutrophilic dermatosis associated with inflammatory bowel disease, rheumatological diseases, haematological disorders and malignancy. PG most commonly affects the lower limbs; may affect peristomal skin, and rarely involves mucosal and internal sites. Genital PG is rare.

A 64-year-old woman with follicular lymphoma in stable partial remission following 8 cycles of chemotherapy including Rituximab therapy, developed painful vulvo-vaginal and peri-anal erosions. These rapidly progressed to frank ulceration with extensive destruction of vulval architecture. She had severe vulval pain without additional systemic or gastrointestinal symptoms, with raised inflammatory markers. She was treated empirically for both candida and herpetic infection with no benefit. Repeated culture of swabs and skin biopsies were negative for viral, bacterial mycobacterial and fungal causes of ulceration; syphilis serology was negative. Computed tomography demonstrated stable lymphoma in partial remission, intact anal sphincter with no fistula formation, and no new malignancy.  Examination under anaesthesia confirmed rectal and urethral integrity despite extensive deep ulceration of the vulva and peri-anal skin. Skin biopsies showed non-specific ulceration without vasculitis or malignancy, the inflammatory infiltrate extended into the subcutaneous adipose tissue and contained neutrophils, lymphocytes, histiocytes and eosinophils. Genital pyoderma gangrenosum was diagnosed. Following discussion with haematology colleagues, treatment of her PG with immunosuppressant medication, without further definitive lymphoma treatment, was commenced. Consensus opinion was that this offered the most favourable risk benefit profile since her lymphoma would require hematopoietic stem cell transplantation to effect cure. Our patient responded well to therapy with prednisolone 0.6 mg/kg/day, ciclosporin 3mg/kg/day and minocycline 100mg daily. By week 7 she was fully healed with scarring. Prednisolone was successfully tapered to 7.5 mg/day over 18 weeks; subsequent attempts at reducing the ciclosporin dose below 1mg/kg/day, resulted in relapses characterised by copious non-offensive sterile discharge and superficial erosions, which subsequently responded to increased ciclosporin dose.  Her lymphoma remains stable on serial imaging with no further recurrence of PG lesions on maintenance ciclosporin 1mg/kg/day. Complications during therapy included adrenal suppression, pulmonary embolism and mild renal impairment. The long-term impact of ciclosporin on her lymphoma prognosis is uncertain and she is closely followed by the haematology service.

Treatment of PG is challenging in cases with established malignancy and there is limited published data on optimum management and outcomes. Pyoderma gangrenosum should be considered as a rare cause of persistent genital ulceration, especially in cases of underlying systemic disease. Ref: ‘Superficial granulomatous pyoderma of the vulva in a patient receiving maintenance rituximab (MabThera) for lymphoma’, Walsh M, Leonard, Bell H, J Low Genital Tract Disease, 2011 April 15(2): 158-60

 

Vulval and anal intra-epithelial neoplasia in a renal transplant patient

S.McCarthy, R. O’Connor, J.F.Bourke

Dermatology Department, South Infirmary Victoria University Hospital, Cork

 

Vulval and anal intraepithelial neoplasia (VIN/AIN) are premalignant conditions, which are frequently associated with human papillomavirus (HPV) infection. Those with multifocal disease or immunosupression have higher rates of surgical treatment failure and progression to invasion.¹

A 44-year old female patient was referred with PV discharge, PR bleeding and an irritated lesion of the left vulva to gynaecology and general surgery services in 2013. She had a history of cadaveric renal transplantation in 1998 and immunosuppression was maintained with tacrolimus, low dose prednisolone and mycophenolate mofetil. Biopsies performed of the left labia minora at this time confirmed a diagnosis of vulval intraepithelial neoplasia, of undifferentiated type with possible stromal invasion seen on one biopsy. Colonoscopy was normal but subsequent biopsies of perianal skin tags in mid 2014 confirmed anal intraepithelial neoplasia. The patient was referred to dermatology in late 2014 due to the extensive involvement of both the vulva and perianal skin with failure to achieve clear margins with surgery. Mycophenolate mofetil was discontinued and sirolimus replaced tacrolimus to lower her overall immunosuppression status. Topical imiquimod was commenced to the vulval and perianal area. Imiquimod 5% cream was applied daily for 10 to 14 days, followed by topical clobetasol propionate ointment [0.05% w/w Ointment] for five to seven days for the intense inflammatory reaction. She repeated this monthly for four months. Repeat punch biopsies of the vulva and perianal area confirmed mild epithelial dysplasia of the perianal area. Her treatment was repeated for a further four months, and the human papilloma virus vaccination was administered.

Vulval- and anal-intraepithelial neoplasia are strongly related clinically and in aetiology. The appearance of VIN and AIN is variable and patients may present with pruritus, or discharge. Lesions may be raised, scaly, white plaques, erythematous, pigmented, fissured or eczematous. Disease is often multifocal and strongly associated with HPV (usually types 6,11,16, and 18) and both are precursors for invasive squamous carcinoma.^{1, 2} Low-grade dysplasia (AIN or VIN I or II) can be managed in an expectant way with regular follow-up. VIN and AIN III can be managed with surgical excision of involved areas however recurrence is common. Vulvectomy has the lowest recurrence rates but leads to psychosexual distress. Topical immunomodulation therapies (Imiquimod 5% cream or cidofovir 1% gel) are emerging as a safe effective alternative, especially in those with a high propensity for recurrence.³ HPV vaccination should be considered in combination with topical therapies as a sustained clinical response has been shown.⁴

1. Scholefield, J. H., D. Harris, and A. Radcliffe. “Guidelines for management of anal intraepithelial neoplasia.” Colorectal diseases1 (2011): 3-10.
2. Joura, Elmar A. “Epidemiology, diagnosis and treatment of vulvar intraepithelial neoplasia.” Current Opinion in Obstetrics and Gynecology1 (2002): 39-43.
3. van Seters, Manon, Marc van Beurden, Fiebo JW ten Kate, Ilse Beckmann, Patricia C. Ewing, Marinus JC Eijkemans, Marjolein J. Kagie et al. “Treatment of vulvar intraepithelial neoplasia with topical imiquimod.” New England Journal of Medicine 358, no. 14 (2008): 1465-1473.
4. Daayana, Sai, Eyad Elkord, U. Winters, M. Pawlita, R. Roden, Peter L. Stern, and Henry C. Kitchener. “Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia.” British journal of cancer 102, no. 7 (2010): 1129-1136.