Table 1. Treatment strategies utilised in 98 CSU patients before and after review at a specialist clinic Medication Regimen
PRN sedating antihistamine PRN non-sedating antihistamine Daily sedating antihistamine Daily non-sedating antihistamine High dose non-sedating antihistamine Additional agents
Prior to specialist review, n (%)
Following specialist review, n (%)
43 (44)
0 (0)
35 (36)
5 (5)
7 (7)
0 (0)
11 (11)
27 (28)
1 (1)
66 (67)
23 (23)
28 (29)
*Additional treatment strategies following specialist review were only employed in patients in whom the response to high dose antihistamines was incomplete.
standard first line therapy of a regular, standard-dose, nonsedating antihistamine. 44% were treated with as-required sedating antihistamines, out of keeping with accepted best practice. Prescribing patterns after specialist review differed considerably from strategies utilised by referring primary care doctors. Non-sedating antihistamines were the main pillar of specialist management and were used at above licensed doses in 67% of cases. 29% of patients required therapy in addition to high dose non-sedating antihistamines, including 5% in whom immunosuppression was required. This data indicates compliance with stepwise EAACI/WAO guideline based management after specialist review. The application of guideline based management resulted in a good outcome in 78% of this previously severely affected cohort. 14% of patients had an adequate outcome, while a further 8% had no improvement despite appropriate management and the use of multiple agents. This retrospective study describes a cohort of patients with long-lived troublesome chronic spontaneous urticaria. Despite significant symptoms, patients were not managed in line with international guidelines prior to specialist review. The main specialist strategy was to prescribe antihistamines on a daily basis and, where required, to increase the dose to above licensed levels. This simple intervention improved outcomes for the majority of patients. The lack of employment of regular high dose antihistamines by primary care practictioners was particularly striking. Liason between primary care and regional specialists with the application of local innovations such as shared care guidelines could lead to more timely and effective intervention. 22% of patients remained symptomatic despite appropriate management using multiple agents. It is this treatment resistant group that is most likely to benefit from specialist input and access to emerging treatment strategies [6]. This study demonstrates poor implementation of EAACI/WAO guidelines for CSU among primary care practitioners. Given the resource limitations on some specialist services, education of primary care physicians and early application of guideline-based CSU management may be a cost efficient way of improving outcome for this neglected patient group.
386
Disclosure. Financial support: none. Conflict of interest: none. 1 Centre for Infection, Immunity, Queen’s University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK 2 Department of Immunology, Royal Victoria Hospital, 274 Grosvenor Road, Belfast, BT12 6BA, UK
Niall P CONLON1 J David M EDGAR2
1. Staubach P, Eckhardt-Henn A, Dechene M, et al. Quality of life in patients with chronic urticaria is differentially impaired and determined by psychiatric comorbidity. Br J Dermatol 2006; 154: 294-8. 2. Kaminski ER, Bethune CA, Jones RB. Complexity of case mix in a regional allergy service. BMC Res Notes 2012; 5103. 3. Chow SKW. Management of chronic urticaria in asia: 2010 AADV consensus guidelines. Asia Pac Allergy 2012; 2: 149-60. 4. Powell RJ, Du Toit GL, Siddique N, et al. BSACI guidelines for the management of chronic urticaria and angio-oedema. Clin Exp Allergy 2007; 37: 631-50. 5. Zuberbier T, Asero R, Bindslev-Jensen C, et al. EAACI/GA(2)LEN/ EDF/WAO guideline: Management of urticaria. Allergy 2009; 64: 1427-43. 6. Maurer M, Rosén K, Hsieh HJ, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med 2013; 368: 924-35. doi:10.1684/ejd.2014.2323
Chronic granulomatous dermatosis as a presenting sign of a lymphoepithelioid Tcell lymphoma (Lennert lymphoma) Lennert lymphoma (LL), under the WHO classification, is defined as a “lymphoepithelioid cell variant of the peripheral T-cell lymphomas, unspecified”, due to its lack of specific clinical features. Lennert lymphoma is primarily a nodal disease which presents with lymphadenopathy, with characteristic pathologic features of epithelioid histiocytes and atypical small lymphoid cells [1]. While skin involvement of LL is known to be infrequent, we report a case of LL that initially presented as atypical granulomatous dermatosis. A 77-year-old female visited our dermatology clinic with dark, erythematous, indurated plaques on her right upper back, shoulder and axilla (figure 1A). The patient complained of pruritus and skin biopsies from the shoulder and axilla revealed chronic granulomatous dermatitis with diffuse lymphocytic infiltration (figure 1B). The possibility of infectious granuloma was ruled out through negative dPAS and Ziehl-Neelsen staining. However, after 3 months, a small palpable nodule was noted in the right axilla; a preliminary examination by ultrasonography raised the possibility of lymphoma and pathologic findings from an excised axillary lymph node revealed proliferation of epithelioid cells and atypical lymphocytes (figure 1C) with immunoreactivity for CD2, CD3 (figure 1D), and CD5, decreased EJD, vol. 24, n◦ 3, May-June 2014
500µm
Yonsei
C13-5213
D.W
(-) Ctl.
lgH (+) Ctl.
F
50bp Marker
D
BM13-682,683
B
Yonsei
A
100µm
C
E
200bp
200bp
100bp
100bp
TCRr(mix II) 100µm
lgH Nested 2'nd
100µm
Figure 1. A) Dark, erythematous, indurated plaques on right upper shoulder and axilla. Three months after the initial presentation, a small palpable nodule in the right axilla was noted. B) Granulomatous inflammation with epithelioid histiocytes and lymphocytes from an erythematous plaque of the shoulder (hematoxylin-eosin; bar, 500 m). C) Excisional biopsy from the palpable axillary nodule revealed lymph node proliferation of small atypical cells and numerous, small, poorly defined clusters of epithelioid histiocytes. Hematoxylin-eosin; bar, 100 m. D) Immunohistochemical staining for CD3 on the infiltrated cells in the skin lesion. Bar, 100 m. E) Retrospective review of the skin lesions also confirmed comparable, pathological changes in the lymph node, such as proliferation of small atypical cells and numerous epithelioid histiocytes (hematoxylin-eosin; bar, 100m). F) The T-cell receptor clonality was confirmed by Southern hybridization (an amplified DNA band between 170-230 bp (white arrow) in the lane of the patient’s sample, which is labeled ‘Yonsei’).
expression of CD7, and negative immunoreactivity for granzyme B, CD30 and CD15. Prominent clusters of epithelioid histiocytes were consistent with diagnostic criteria for lymphoepithelioid lymphoma [1]. The patient was diagnosed as stage IV, with the involvement of no organs other than the skin, through imaging studies and bone marrow aspiration biopsy. A careful retrospective review of the skin lesions also confirmed the involvement of lymphoma within the skin (figure 1E). Infiltrating T cells expressed CD8 but not CD4, and they were negative for CD7 antigen but not for CD2 or CD3. Analysis of Southern blots detected rearrangement of the T-cell receptor gene, but semi-nested PCR failed to reveal any rearrangement of the immunoglobulin heavychain gene (figure 1F). Proliferating cells did not express CD20, CD30 or granzyme B, but in situ hybridization of Epstein-Barr virus-encoded small RNA (EBER) showed positive nuclear signals in the tumor cells. The prominent population of CD8+ cells, rather than CD4 expression, supports previous investigations of LL as being derived from a CD8+ cytotoxic T cell [2]. Cutaneous manifestations are rare as initial presentations in LL. We highlight the need for awareness about cutaneous involvement of LL and suggest that the presence of epithelioid histiocytes and small lymphoid cells in skin can be overlooked as a mere granulomatous inflammatory reaction. Previous anecdotal reports have shown a granuloma annulare-like skin lesion, prurigo nodularis or non-specific reactive dermatosis without cellular atypia as cutaneous manifestations of LL [1, 3, 4]. However these cases were suggested to be reactive skin responses arising at a distant focus from lymphoma. There have been reports of cutaneous involvement in LL arising before a nodal lesion but the atypical cells were only confined to a deeper layer of skin [5], or they appeared as small asymptomatic papules [6]. Yet, our case differs, as the initial presentation was not in the usual characteristic nodular structure but rather a polymorphic plaque, making the diagnosis of lymphoma difficult EJD, vol. 24, n◦ 3, May-June 2014
before the lymph node confirmation. Therefore, cutaneous involvement clinically mimicking a chronic granulomatous dermatitis prior to the development of nodal lymphoma in our patient could be noted as an uncommon presentation. We believe that the relatively indolent, cellular atypia in a skin specimen can be easily overlooked in cutaneous involvement of LL. Both careful physical examination and lymph node biopsy should be carried out because of the possible aggressive nature of LL, which would necessitate an intensive treatment. Disclosure. Financial support: none. Conflict of interest: none.
1 Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, 2 Department of Pathology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Seoul, Korea
Hemin LEE1 Dae Suk KIM1 Soo Hee KIM2 Do Young KIM1
1. Patsouris E, Engelhard M, Zwingers T, et al. Lymphoepithelioid cell lymphoma (Lennert’s lymphoma): clinical features derived from analysis of 108 cases. Br J Haemat 1993; 84: 346-8. 2. Geissinger E, Odenwald T, Lee S. Nodal peripheral T-cell lymphomas and, in particular, their lymphoepithelioid (Lennert’s) variant are often derived from CD8+ cytotoxic T-cells. Virchows Arch 2004; 445: 334-43. 3. Bhushan M, Craven NM, Armstrong GR, et al. Lymphoepithelioid cell lymphoma (Lennert’s lymphoma) presenting as atypical granuloma annulare. Br J Dermatol 2000; 142: 776-80. 4. Seeburger J, Anderson-Wilms N, Jacobs R. Lennert’s lymphomapresenting as prurigo nodularis. Cutis 1993; 51: 355. 5. Kiesewetter F, Haneke E, Lennert K, et al. Cutaneous lymphoepithelioid lymphoma (Lennert’s lymphoma). Combined immunohistological, ultrastructural, and DNA-flow-cytometric analysis. Am J Dermatopathol 1989; 11: 549-54. 6. Massone C, Basso M, Rongioletti F. Cutaneous presentation of recurrence of lymphoepithelioid T-cell lymphoma (Lennert’s lymphoma). Clin Exp Dermatol 2005; 30: 155-7. doi:10.1684/ejd.2014.2328
Treatment of recalcitrant erythrodermic psoriasis with ustekinumab Erythrodermic psoriasis (EP) can be challenging to treat since several factors, such as failure or intolerance, limit favourable outcomes with traditional therapies [1]. The conventional treatments recommended for EP are methotrexate, oral retinoids and cyclosporine [2], although systemic steroids are still used, especially in severe and unstable forms, since they usually induce a rapid clinical improvement [2, 3]. Recently, some cases of EP have been successfully treated with biological agents, including tumor
387
PRN sedating antihistamine PRN non-sedating antihistamine Daily sedating antihistamine Daily non-sedating antihistamine High dose non-sedating antihistamine Additional agents
Prior to specialist review, n (%)
Following specialist review, n (%)
43 (44)
0 (0)
35 (36)
5 (5)
7 (7)
0 (0)
11 (11)
27 (28)
1 (1)
66 (67)
23 (23)
28 (29)
*Additional treatment strategies following specialist review were only employed in patients in whom the response to high dose antihistamines was incomplete.
standard first line therapy of a regular, standard-dose, nonsedating antihistamine. 44% were treated with as-required sedating antihistamines, out of keeping with accepted best practice. Prescribing patterns after specialist review differed considerably from strategies utilised by referring primary care doctors. Non-sedating antihistamines were the main pillar of specialist management and were used at above licensed doses in 67% of cases. 29% of patients required therapy in addition to high dose non-sedating antihistamines, including 5% in whom immunosuppression was required. This data indicates compliance with stepwise EAACI/WAO guideline based management after specialist review. The application of guideline based management resulted in a good outcome in 78% of this previously severely affected cohort. 14% of patients had an adequate outcome, while a further 8% had no improvement despite appropriate management and the use of multiple agents. This retrospective study describes a cohort of patients with long-lived troublesome chronic spontaneous urticaria. Despite significant symptoms, patients were not managed in line with international guidelines prior to specialist review. The main specialist strategy was to prescribe antihistamines on a daily basis and, where required, to increase the dose to above licensed levels. This simple intervention improved outcomes for the majority of patients. The lack of employment of regular high dose antihistamines by primary care practictioners was particularly striking. Liason between primary care and regional specialists with the application of local innovations such as shared care guidelines could lead to more timely and effective intervention. 22% of patients remained symptomatic despite appropriate management using multiple agents. It is this treatment resistant group that is most likely to benefit from specialist input and access to emerging treatment strategies [6]. This study demonstrates poor implementation of EAACI/WAO guidelines for CSU among primary care practitioners. Given the resource limitations on some specialist services, education of primary care physicians and early application of guideline-based CSU management may be a cost efficient way of improving outcome for this neglected patient group.
386
Disclosure. Financial support: none. Conflict of interest: none. 1 Centre for Infection, Immunity, Queen’s University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK 2 Department of Immunology, Royal Victoria Hospital, 274 Grosvenor Road, Belfast, BT12 6BA, UK
Niall P CONLON1 J David M EDGAR2
1. Staubach P, Eckhardt-Henn A, Dechene M, et al. Quality of life in patients with chronic urticaria is differentially impaired and determined by psychiatric comorbidity. Br J Dermatol 2006; 154: 294-8. 2. Kaminski ER, Bethune CA, Jones RB. Complexity of case mix in a regional allergy service. BMC Res Notes 2012; 5103. 3. Chow SKW. Management of chronic urticaria in asia: 2010 AADV consensus guidelines. Asia Pac Allergy 2012; 2: 149-60. 4. Powell RJ, Du Toit GL, Siddique N, et al. BSACI guidelines for the management of chronic urticaria and angio-oedema. Clin Exp Allergy 2007; 37: 631-50. 5. Zuberbier T, Asero R, Bindslev-Jensen C, et al. EAACI/GA(2)LEN/ EDF/WAO guideline: Management of urticaria. Allergy 2009; 64: 1427-43. 6. Maurer M, Rosén K, Hsieh HJ, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med 2013; 368: 924-35. doi:10.1684/ejd.2014.2323
Chronic granulomatous dermatosis as a presenting sign of a lymphoepithelioid Tcell lymphoma (Lennert lymphoma) Lennert lymphoma (LL), under the WHO classification, is defined as a “lymphoepithelioid cell variant of the peripheral T-cell lymphomas, unspecified”, due to its lack of specific clinical features. Lennert lymphoma is primarily a nodal disease which presents with lymphadenopathy, with characteristic pathologic features of epithelioid histiocytes and atypical small lymphoid cells [1]. While skin involvement of LL is known to be infrequent, we report a case of LL that initially presented as atypical granulomatous dermatosis. A 77-year-old female visited our dermatology clinic with dark, erythematous, indurated plaques on her right upper back, shoulder and axilla (figure 1A). The patient complained of pruritus and skin biopsies from the shoulder and axilla revealed chronic granulomatous dermatitis with diffuse lymphocytic infiltration (figure 1B). The possibility of infectious granuloma was ruled out through negative dPAS and Ziehl-Neelsen staining. However, after 3 months, a small palpable nodule was noted in the right axilla; a preliminary examination by ultrasonography raised the possibility of lymphoma and pathologic findings from an excised axillary lymph node revealed proliferation of epithelioid cells and atypical lymphocytes (figure 1C) with immunoreactivity for CD2, CD3 (figure 1D), and CD5, decreased EJD, vol. 24, n◦ 3, May-June 2014
500µm
Yonsei
C13-5213
D.W
(-) Ctl.
lgH (+) Ctl.
F
50bp Marker
D
BM13-682,683
B
Yonsei
A
100µm
C
E
200bp
200bp
100bp
100bp
TCRr(mix II) 100µm
lgH Nested 2'nd
100µm
Figure 1. A) Dark, erythematous, indurated plaques on right upper shoulder and axilla. Three months after the initial presentation, a small palpable nodule in the right axilla was noted. B) Granulomatous inflammation with epithelioid histiocytes and lymphocytes from an erythematous plaque of the shoulder (hematoxylin-eosin; bar, 500 m). C) Excisional biopsy from the palpable axillary nodule revealed lymph node proliferation of small atypical cells and numerous, small, poorly defined clusters of epithelioid histiocytes. Hematoxylin-eosin; bar, 100 m. D) Immunohistochemical staining for CD3 on the infiltrated cells in the skin lesion. Bar, 100 m. E) Retrospective review of the skin lesions also confirmed comparable, pathological changes in the lymph node, such as proliferation of small atypical cells and numerous epithelioid histiocytes (hematoxylin-eosin; bar, 100m). F) The T-cell receptor clonality was confirmed by Southern hybridization (an amplified DNA band between 170-230 bp (white arrow) in the lane of the patient’s sample, which is labeled ‘Yonsei’).
expression of CD7, and negative immunoreactivity for granzyme B, CD30 and CD15. Prominent clusters of epithelioid histiocytes were consistent with diagnostic criteria for lymphoepithelioid lymphoma [1]. The patient was diagnosed as stage IV, with the involvement of no organs other than the skin, through imaging studies and bone marrow aspiration biopsy. A careful retrospective review of the skin lesions also confirmed the involvement of lymphoma within the skin (figure 1E). Infiltrating T cells expressed CD8 but not CD4, and they were negative for CD7 antigen but not for CD2 or CD3. Analysis of Southern blots detected rearrangement of the T-cell receptor gene, but semi-nested PCR failed to reveal any rearrangement of the immunoglobulin heavychain gene (figure 1F). Proliferating cells did not express CD20, CD30 or granzyme B, but in situ hybridization of Epstein-Barr virus-encoded small RNA (EBER) showed positive nuclear signals in the tumor cells. The prominent population of CD8+ cells, rather than CD4 expression, supports previous investigations of LL as being derived from a CD8+ cytotoxic T cell [2]. Cutaneous manifestations are rare as initial presentations in LL. We highlight the need for awareness about cutaneous involvement of LL and suggest that the presence of epithelioid histiocytes and small lymphoid cells in skin can be overlooked as a mere granulomatous inflammatory reaction. Previous anecdotal reports have shown a granuloma annulare-like skin lesion, prurigo nodularis or non-specific reactive dermatosis without cellular atypia as cutaneous manifestations of LL [1, 3, 4]. However these cases were suggested to be reactive skin responses arising at a distant focus from lymphoma. There have been reports of cutaneous involvement in LL arising before a nodal lesion but the atypical cells were only confined to a deeper layer of skin [5], or they appeared as small asymptomatic papules [6]. Yet, our case differs, as the initial presentation was not in the usual characteristic nodular structure but rather a polymorphic plaque, making the diagnosis of lymphoma difficult EJD, vol. 24, n◦ 3, May-June 2014
before the lymph node confirmation. Therefore, cutaneous involvement clinically mimicking a chronic granulomatous dermatitis prior to the development of nodal lymphoma in our patient could be noted as an uncommon presentation. We believe that the relatively indolent, cellular atypia in a skin specimen can be easily overlooked in cutaneous involvement of LL. Both careful physical examination and lymph node biopsy should be carried out because of the possible aggressive nature of LL, which would necessitate an intensive treatment. Disclosure. Financial support: none. Conflict of interest: none.
1 Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, 2 Department of Pathology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Seoul, Korea
Hemin LEE1 Dae Suk KIM1 Soo Hee KIM2 Do Young KIM1
1. Patsouris E, Engelhard M, Zwingers T, et al. Lymphoepithelioid cell lymphoma (Lennert’s lymphoma): clinical features derived from analysis of 108 cases. Br J Haemat 1993; 84: 346-8. 2. Geissinger E, Odenwald T, Lee S. Nodal peripheral T-cell lymphomas and, in particular, their lymphoepithelioid (Lennert’s) variant are often derived from CD8+ cytotoxic T-cells. Virchows Arch 2004; 445: 334-43. 3. Bhushan M, Craven NM, Armstrong GR, et al. Lymphoepithelioid cell lymphoma (Lennert’s lymphoma) presenting as atypical granuloma annulare. Br J Dermatol 2000; 142: 776-80. 4. Seeburger J, Anderson-Wilms N, Jacobs R. Lennert’s lymphomapresenting as prurigo nodularis. Cutis 1993; 51: 355. 5. Kiesewetter F, Haneke E, Lennert K, et al. Cutaneous lymphoepithelioid lymphoma (Lennert’s lymphoma). Combined immunohistological, ultrastructural, and DNA-flow-cytometric analysis. Am J Dermatopathol 1989; 11: 549-54. 6. Massone C, Basso M, Rongioletti F. Cutaneous presentation of recurrence of lymphoepithelioid T-cell lymphoma (Lennert’s lymphoma). Clin Exp Dermatol 2005; 30: 155-7. doi:10.1684/ejd.2014.2328
Treatment of recalcitrant erythrodermic psoriasis with ustekinumab Erythrodermic psoriasis (EP) can be challenging to treat since several factors, such as failure or intolerance, limit favourable outcomes with traditional therapies [1]. The conventional treatments recommended for EP are methotrexate, oral retinoids and cyclosporine [2], although systemic steroids are still used, especially in severe and unstable forms, since they usually induce a rapid clinical improvement [2, 3]. Recently, some cases of EP have been successfully treated with biological agents, including tumor
387
