CED
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Propranolol: a novel treatment for angiolymphoid hyperplasia with eosinophilia C. Horst and N. Kapur Department of Dermatology, The Whittington Hospital, London, UK doi:10.1111/ced.12412
Summary
Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, idiopathic disease that manifests as dermal or subcutaneous red or brown papules or nodules, most commonly on the head and neck. Histologically, ALHE is characterized by vascular proliferation with epithelioid endothelial cells with surrounding lymphocytic and eosinophilic infiltrate. There may be an accompanying serum eosinophilia and local lymphadenopathy. We report a case of a 32-year-old woman who presented with multiple erythematous nodules in the periauricular area and the vertex of her scalp. The nodules had been present for several months. Surgical removal of one of the lesions confirmed the histological diagnosis of ALHE. The patient was started on oral propranolol (40 mg once daily) in an effort to reduce the vascular component of the lesions. Within 6 weeks, the patient noted that several of the lesions had decreased in size, and all were less erythematous. Propranolol was subsequently stopped within a few months of initiating treatment. One lesion recurred over a year later, and propranolol was then restarted. No new lesions occurred after 2 years of follow-up.
Angiolymphoid hyperplasia with eosinophilia (ALHE) is a histological description of painless vascular lesions that can appear as erythematous papules or brown nodules, occurring mainly in the cutis and subcutis of the head and neck. Also known as epithelioid haemangioma, inflammatory angiomatous nodule and atypical granuloma, among other names, the condition is uncommon and benign, and often manifests in young women.1 There may also be a hormonal component to the lesions, as they tend to expand and proliferate under the influence of oestrogen. The histological changes underlying ALHE include reactive proliferation of capillary vessels, an excess of mast cells and eosinophilic infiltration, and lymphadenopathy Correspondence: Carolyn Horst, Department of Dermatology, The Whittington Hospital, Magdala Avenue, London, N19 5NF, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 16 February 2014
810
Clinical and Experimental Dermatology (2014) 39, pp810–812
local to the lesion.2 Multiple treatments have been reported, including excision, steroid injections, biological therapies and phototherapy, but none with great or reproducible success.
Report A 32-year-old woman presented to our clinic in August 2010, with multiple, red–brown, pedunculated and nodular lesions in the left periauricular area and the vertex of her scalp (Fig. 1a,b). She had a background history of multiple pilar cysts on her scalp, but the new lesions had a different consistency from the pilar cysts, and had only appeared recently, during her pregnancy with her sixth child. The lesions began with pruritus in the area of the lesion, then they became scabbed and raised, and occasionally bled. On initial examination, the lesions appeared to be secondarily infected, and the patient was prescribed erythromycin to clear the infection. She was given a
ª 2014 British Association of Dermatologists
Propranolol: treatment for angiolymphoid hyperplasia with eosinophilia C. Horst and N. Kapur
(a)
(b) Figure 2 Biopsy taken from left periauricular area showing
marked eosinophilic infiltrate around a central vessel with endothelial cell hyperplasia (haematoxylin and eosin, original magnification 9 10).
Figure 1 (a,b) The left periauricular area, showing the large,
erythematous nodules of angiolymphoid hyperplasia with eosinophilia in November 2010.
working diagnosis of Kimura disease (KD), and a biopsy was taken once the secondary infection had resolved. Histological examination found expansion of the dermis by vascular proliferation, along with the presence of plump endothelial cells, and considerable eosinophil and lymphocyte infiltration (Fig. 2). A diagnosis of ALHE was made. By October 2010, three new lesions had appeared at the vertex of the patient’s scalp. It was recommended that the patient change contraception to a nonhormonal method, and she arranged to have a coil inserted. Given the number, site, size and location of the lesions, surgical excision was not considered a desirable option, so the patient was given propranolol 40 mg once daily to reduce the vascular component and therefore the size of the lesions by a noninvasive method. This dose of propranolol was chosen in line with guidance on decreasing the vasculature of congenital haemangiomas in children. On review 6 weeks after initiating propranolol, there was a considerable
ª 2014 British Association of Dermatologists
improvement; two of the lesions had decreased in size and the others had become less erythematous. No new lesions had appeared in that time. The patient was advised to continue on propranolol. The patient ceased taking propranolol several months later, and she re-presented to a different clinic with similar lesions in January 2012, a little over a year after her last follow-up with us. The new lesions were thought to be pilar cysts, but on removal and histological examination, they were found to be ALHE as well. The patient resumed propranolol at this time and no new lesions were seen in May 2012 when she was reviewed in our clinic. The existing lesions had not increased in size. Throughout her treatment, the patient’s blood pressure never dipped below 96/64, and on average was 106/68; before she initiated treatment, her blood pressure was 117/73. She did not report any adverse effects of the medication. She returned to our clinic in July 2012, when she was found to have secondarily infected pilar cysts on the vertex of her scalp, and was treated with erythromycin. The most recent followup was in January 2014; she was asymptomatic, there were no new lesions, and the only mark in the periaricular area was scarring at the original biopsy site (Fig. 3). ALHE was originally thought to be at one end of a disease spectrum, with KD at the other. The similar features of these two conditions include the lesion location (head and neck), and some aspects of the histopathology (lymphoid and vascular proliferation).3
Clinical and Experimental Dermatology (2014) 39, pp810–812
811
Propranolol: treatment for angiolymphoid hyperplasia with eosinophilia C. Horst and N. Kapur
Learning points
•
Figure 3 Left periaricular area showing the biopsy site but no
other signs of the angiolymphoid hyperplasia with eosinophilia in January 2014.
However, they are different in lesion persistence (KD lesions tend to endure longer), their target demographic (men vs. women) and the presence of lymphoid germinal centres (absent in ALHE).4 Regardless of the debate over whether or not they are the same disease at different stages or severity, neither type of lesion has a definitive management. Many approaches to treating ALHE have been tried since the condition was originally described over 40 years ago. These include conventional therapies such as steroids (injected and systemic), methotrexate, cryotherapy, phototherapy and surgical excision, as well as new therapies targeting cytokines (including topical imiquimod), interleukin-5 (meolizumab)5,6 and vascular endothelial growth factor-A (bevcizumab).7 These latter approaches have been reported as successful, but given the cost of biological therapies, may be untenable as a treatment in many clinical situations. There is only one previous report of the use of oral propranolol for ALHE, but the lesions in that patient presented as a superotemporal orbital mass affecting his vision, instead of the more typical, subcutaneous periauricular lesions.8 As reported above, the use of propranolol in this patient, with a typical presentation of ALHE, was successful in reducing the growth rate of several lesions and reducing the size of several more lesions. We believe that the success of both monoclonal antibody therapy and propranolol is due to them targeting the vascular proliferative element of ALHE. Given the expense of monoclonal antibody treatment, propranolol may offer an inexpensive alternative as first-line therapy for ALHE.
812
Clinical and Experimental Dermatology (2014) 39, pp810–812
ALHE is a difficult condition to treat, and there is little consistent evidence for many types of treatment approaches. • Excision has been commonly thought to be the most valuable intervention. • Propranolol may successfully address the vascular aspect of the lesions, preventing growth and causing a reduction in size in the lesions. • Monoclonal therapies such as bevacizumab and mepolizumab may also be successful, but are unlikely to be used as a first-line treatment, given their expense. • The condition may occur on a background of other dermatological conditions, including recurrent pilar cysts. • Recognition of ALHE as a different condition is important for appropriate management.
References 1 Botet MV, Sanchez JL. Angiolymphoid hyper-plasia with eosinophilia: report of a case and a review of the literature. J Dermatol Surg Oncol 1978; 4: 931–6. 2 Wells GC, Whimster IW. Subcutaneous angiolymphoid hyperplasia with eosinophilia. Br J Dermatol 1969; 81: 1–14. 3 Chong WS, Thomas A, Coh CL. Kimura’s disease and angiolymphoid hyperplasia with eosinophilia: two disease entities in the same patient. Int J Dermatol 2006; 45: 39– 145. 4 Kuo TT, Lee YS, Chan HL. Kimura’s disease. Involvement of regional lymph nodes and distinction from angiolymphoid hyperplasia with eosinophilia. Am J Surg Pathol 1988; 12: 843–54. 5 Isohisa T, Masuda K, Nakai N et al. Angiolymphoid Hyperplasia with eosinophils treated successfully with imiquimod. Int J Dermatol 2014; 53: e43–4. 6 Braun-Falco M, Fischer S, Plotz SG et al. Angiolymphoid hyperplasia with eosinophilia treated with anti-interleukin 5 antibody (mepolizumab). Br J Dermatol 2004; 151: 1103–4. 7 Kahuna A, Lee B, Flint A et al. Periocular epithelioid hemangioma: response to bevacizumab and vascaular pathogenesis. Arch Ophthalmol 2012; 130: 1209–12. 8 Moss H, Sines D, Blatt J et al. Epithelioid hemangioma responsive to oral propranolol. Ophthal Plast Reconstr Surg 2012; 28: e88–90.
ª 2014 British Association of Dermatologists
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Propranolol: a novel treatment for angiolymphoid hyperplasia with eosinophilia C. Horst and N. Kapur Department of Dermatology, The Whittington Hospital, London, UK doi:10.1111/ced.12412
Summary
Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, idiopathic disease that manifests as dermal or subcutaneous red or brown papules or nodules, most commonly on the head and neck. Histologically, ALHE is characterized by vascular proliferation with epithelioid endothelial cells with surrounding lymphocytic and eosinophilic infiltrate. There may be an accompanying serum eosinophilia and local lymphadenopathy. We report a case of a 32-year-old woman who presented with multiple erythematous nodules in the periauricular area and the vertex of her scalp. The nodules had been present for several months. Surgical removal of one of the lesions confirmed the histological diagnosis of ALHE. The patient was started on oral propranolol (40 mg once daily) in an effort to reduce the vascular component of the lesions. Within 6 weeks, the patient noted that several of the lesions had decreased in size, and all were less erythematous. Propranolol was subsequently stopped within a few months of initiating treatment. One lesion recurred over a year later, and propranolol was then restarted. No new lesions occurred after 2 years of follow-up.
Angiolymphoid hyperplasia with eosinophilia (ALHE) is a histological description of painless vascular lesions that can appear as erythematous papules or brown nodules, occurring mainly in the cutis and subcutis of the head and neck. Also known as epithelioid haemangioma, inflammatory angiomatous nodule and atypical granuloma, among other names, the condition is uncommon and benign, and often manifests in young women.1 There may also be a hormonal component to the lesions, as they tend to expand and proliferate under the influence of oestrogen. The histological changes underlying ALHE include reactive proliferation of capillary vessels, an excess of mast cells and eosinophilic infiltration, and lymphadenopathy Correspondence: Carolyn Horst, Department of Dermatology, The Whittington Hospital, Magdala Avenue, London, N19 5NF, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 16 February 2014
810
Clinical and Experimental Dermatology (2014) 39, pp810–812
local to the lesion.2 Multiple treatments have been reported, including excision, steroid injections, biological therapies and phototherapy, but none with great or reproducible success.
Report A 32-year-old woman presented to our clinic in August 2010, with multiple, red–brown, pedunculated and nodular lesions in the left periauricular area and the vertex of her scalp (Fig. 1a,b). She had a background history of multiple pilar cysts on her scalp, but the new lesions had a different consistency from the pilar cysts, and had only appeared recently, during her pregnancy with her sixth child. The lesions began with pruritus in the area of the lesion, then they became scabbed and raised, and occasionally bled. On initial examination, the lesions appeared to be secondarily infected, and the patient was prescribed erythromycin to clear the infection. She was given a
ª 2014 British Association of Dermatologists
Propranolol: treatment for angiolymphoid hyperplasia with eosinophilia C. Horst and N. Kapur
(a)
(b) Figure 2 Biopsy taken from left periauricular area showing
marked eosinophilic infiltrate around a central vessel with endothelial cell hyperplasia (haematoxylin and eosin, original magnification 9 10).
Figure 1 (a,b) The left periauricular area, showing the large,
erythematous nodules of angiolymphoid hyperplasia with eosinophilia in November 2010.
working diagnosis of Kimura disease (KD), and a biopsy was taken once the secondary infection had resolved. Histological examination found expansion of the dermis by vascular proliferation, along with the presence of plump endothelial cells, and considerable eosinophil and lymphocyte infiltration (Fig. 2). A diagnosis of ALHE was made. By October 2010, three new lesions had appeared at the vertex of the patient’s scalp. It was recommended that the patient change contraception to a nonhormonal method, and she arranged to have a coil inserted. Given the number, site, size and location of the lesions, surgical excision was not considered a desirable option, so the patient was given propranolol 40 mg once daily to reduce the vascular component and therefore the size of the lesions by a noninvasive method. This dose of propranolol was chosen in line with guidance on decreasing the vasculature of congenital haemangiomas in children. On review 6 weeks after initiating propranolol, there was a considerable
ª 2014 British Association of Dermatologists
improvement; two of the lesions had decreased in size and the others had become less erythematous. No new lesions had appeared in that time. The patient was advised to continue on propranolol. The patient ceased taking propranolol several months later, and she re-presented to a different clinic with similar lesions in January 2012, a little over a year after her last follow-up with us. The new lesions were thought to be pilar cysts, but on removal and histological examination, they were found to be ALHE as well. The patient resumed propranolol at this time and no new lesions were seen in May 2012 when she was reviewed in our clinic. The existing lesions had not increased in size. Throughout her treatment, the patient’s blood pressure never dipped below 96/64, and on average was 106/68; before she initiated treatment, her blood pressure was 117/73. She did not report any adverse effects of the medication. She returned to our clinic in July 2012, when she was found to have secondarily infected pilar cysts on the vertex of her scalp, and was treated with erythromycin. The most recent followup was in January 2014; she was asymptomatic, there were no new lesions, and the only mark in the periaricular area was scarring at the original biopsy site (Fig. 3). ALHE was originally thought to be at one end of a disease spectrum, with KD at the other. The similar features of these two conditions include the lesion location (head and neck), and some aspects of the histopathology (lymphoid and vascular proliferation).3
Clinical and Experimental Dermatology (2014) 39, pp810–812
811
Propranolol: treatment for angiolymphoid hyperplasia with eosinophilia C. Horst and N. Kapur
Learning points
•
Figure 3 Left periaricular area showing the biopsy site but no
other signs of the angiolymphoid hyperplasia with eosinophilia in January 2014.
However, they are different in lesion persistence (KD lesions tend to endure longer), their target demographic (men vs. women) and the presence of lymphoid germinal centres (absent in ALHE).4 Regardless of the debate over whether or not they are the same disease at different stages or severity, neither type of lesion has a definitive management. Many approaches to treating ALHE have been tried since the condition was originally described over 40 years ago. These include conventional therapies such as steroids (injected and systemic), methotrexate, cryotherapy, phototherapy and surgical excision, as well as new therapies targeting cytokines (including topical imiquimod), interleukin-5 (meolizumab)5,6 and vascular endothelial growth factor-A (bevcizumab).7 These latter approaches have been reported as successful, but given the cost of biological therapies, may be untenable as a treatment in many clinical situations. There is only one previous report of the use of oral propranolol for ALHE, but the lesions in that patient presented as a superotemporal orbital mass affecting his vision, instead of the more typical, subcutaneous periauricular lesions.8 As reported above, the use of propranolol in this patient, with a typical presentation of ALHE, was successful in reducing the growth rate of several lesions and reducing the size of several more lesions. We believe that the success of both monoclonal antibody therapy and propranolol is due to them targeting the vascular proliferative element of ALHE. Given the expense of monoclonal antibody treatment, propranolol may offer an inexpensive alternative as first-line therapy for ALHE.
812
Clinical and Experimental Dermatology (2014) 39, pp810–812
ALHE is a difficult condition to treat, and there is little consistent evidence for many types of treatment approaches. • Excision has been commonly thought to be the most valuable intervention. • Propranolol may successfully address the vascular aspect of the lesions, preventing growth and causing a reduction in size in the lesions. • Monoclonal therapies such as bevacizumab and mepolizumab may also be successful, but are unlikely to be used as a first-line treatment, given their expense. • The condition may occur on a background of other dermatological conditions, including recurrent pilar cysts. • Recognition of ALHE as a different condition is important for appropriate management.
References 1 Botet MV, Sanchez JL. Angiolymphoid hyper-plasia with eosinophilia: report of a case and a review of the literature. J Dermatol Surg Oncol 1978; 4: 931–6. 2 Wells GC, Whimster IW. Subcutaneous angiolymphoid hyperplasia with eosinophilia. Br J Dermatol 1969; 81: 1–14. 3 Chong WS, Thomas A, Coh CL. Kimura’s disease and angiolymphoid hyperplasia with eosinophilia: two disease entities in the same patient. Int J Dermatol 2006; 45: 39– 145. 4 Kuo TT, Lee YS, Chan HL. Kimura’s disease. Involvement of regional lymph nodes and distinction from angiolymphoid hyperplasia with eosinophilia. Am J Surg Pathol 1988; 12: 843–54. 5 Isohisa T, Masuda K, Nakai N et al. Angiolymphoid Hyperplasia with eosinophils treated successfully with imiquimod. Int J Dermatol 2014; 53: e43–4. 6 Braun-Falco M, Fischer S, Plotz SG et al. Angiolymphoid hyperplasia with eosinophilia treated with anti-interleukin 5 antibody (mepolizumab). Br J Dermatol 2004; 151: 1103–4. 7 Kahuna A, Lee B, Flint A et al. Periocular epithelioid hemangioma: response to bevacizumab and vascaular pathogenesis. Arch Ophthalmol 2012; 130: 1209–12. 8 Moss H, Sines D, Blatt J et al. Epithelioid hemangioma responsive to oral propranolol. Ophthal Plast Reconstr Surg 2012; 28: e88–90.
ª 2014 British Association of Dermatologists
