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Angiokeratomas in a bathing suit distribution
1255
1112
Timely access to tertiary dermatologic care may reduce diagnostic delays and unnecessary healthcare services Yara Abdou, MD, University of New Mexico, School of Medicine, Albuquerque, NM, United States; Ifeoma Aguanunu, MD, MPH, University of Illinois at Chicago, College of Medicine, Chicago, IL, United States; Christine Lohse, Mayo Clinic, College of Medicine, Rochester, MN, United States; Nneka Comfere, MD, Mayo Clinic, College of Medicine, Rochester, MN, United States Skin concerns are the most common (49.7%) reason why patients visited their doctor and account for $39.3 billion in medical costs. Primary care practitioners including physician extenders with variable dermatologic expertise commonly provide dermatologic care. Increasing demand for dermatologic care in an aging population, long wait times and disparities in access are likely to further exacerbate these trends. The primary objective of this study is to assess rates of diagnostic delay, diagnostic discordance and health care utilization in referrals to a tertiary dermatology practice. A retrospective analysis of clinical and demographic characteristics and health care service utilization of 228 patients referred to the dermatology department at Mayo Clinic, Rochester (MCR) in August 2012 was performed. Patients referred to the MCR dermatology practice were predominantly women (60%), aged 55 years, had visited a provider of dermatologic services 148 miles away, and were referred by a primary care practitioner (53%). 11% of referrals had 2 or 3 prior diagnoses and 30% had seen 2 or more providers prior to their referral. 13% of referrals had $2 prior skin biopsies and 33% had $4 previous therapies. Clinical and pathologic diagnostic discordance were noted in 32% and 9% respectively, of all patients referred to the dermatology practice. Significant differences in the proportion of clinically discordant diagnoses rendered by primary care practitioners relative to dermatologists were observed (68% vs 25%; P ¼.023). Diagnostic delay of [2 years occurred in 44% of referred patients. The proportions of referring professionals from dermatology, primary care, and ‘other’ specialties with a[2 year lag in diagnosis were 48%, 37%, and 63%, respectively (P ¼.039). The correlation coefficient for the association between miles from Mayo and time lag in diagnosis was 0.37 (P \.001). The proportions of patients with clinical information that was provided, not provided, and not documented with a [2 year lag in diagnosis were 25%, 73%, and 48%, respectively (P ¼.001). Patients who received an exit diagnosis in the category of inflammatory dermatoses had the highest mean numbers of previous diagnoses (1.3), previous providers (1.8) and previous therapies (3.4), relative to those with nonmelanocytic and melanocytic proliferations. Direct and timely access to a tertiary practice for dermatologic care may facilitate accurate, timely and cost effective diagnosis.
A rare dyschromatosis possibly associated with malignancy Niharika Bansal, Solihull Hospital, Solihull, United Kingdom; Manjit Kaur, Heart of England Hospitals NHS Foundation Trust, Solihull, United Kingdom; Trevor Cole, West Midlands Regional Genetics, Birmingham, United Kingdom; Celia Moss, Birmingham Children’s Hospital, Birmingham, United Kingdom; Annette Loffeld, Solihull Hospital, Solihull, United Kingdom; Chamandeep Thind, Worcester Royal Hospital, Worcester, United Kingdom; John Lee, St John’s Institute of Dermatology, London, United Kingdom; Takuya Takeichi, St John’s Institute of Dermatology, London, United Kingdom; Marie O’Donnell, Birmingham Women’s Hospital NHSFT, Birmingham, United Kingdom; Alexis Cuell, City Hospital, Birmingham, United Kingeom; John McGrath, King’s College London, London, United Kingdom
Commercial support: None identified.
The dyschromatoses are a group of pigmentary disorders characterized by mixed hypo- and hyperpigmented lesions. Mutations in 14 genes have been reported in the inherited dyschromatoses, including the c-kit receptor ligand (KITLG). KITLG mutations lead to diverse skin phenotypes, including autosomal dominant familial progressive hyper- and hypopigmentation (FPHH), a subtype of familial progressive hyperpigmentation and dyschromatosis universalis hereditaria type 2. We describe 2 families with FPHH in whom we identified previously unreported mutations in KITLG. In addition, skin and internal malignancies were noted in both pedigrees, raising the possibility of FPHH being a new cancer-associated genodermatosis. Family 1: 3 generations of a Caucasian nonconsanguineous family presented with a progressive pigmentary disorder consisting of hypo- and hyperpigmented macules. Marked tanning and thickening of sun exposed skin was reported, changes also seen on nonesun exposed areas including palms and soles. The 62-year-old grandfather had a history of pharyngeal cancer and was found to have two primary superficial spreading melanomas on his back. DNA analysis revealed a novel germline heterozygous missense mutation (c.101C [ A: p.Thr34Asn) in KITLG in the proband, father, grandfather but not in the proband’s unaffected sister. Family 2: A 36-year-old British Caucasian woman reported progressive hyperpigmentation and dark macules with onset in early childhood. The pigmentary changes were seen in both sun-exposed and nonexposed skin, including palms and soles. She had a history of papillary thyroid cancer. 2 of her 3 sons showed similar skin changes, with increased pigmentation of skin and striking hypo- and hyperpigmented macules. DNA analysis revealed a novel germline heterozygous missense mutation in KITLG (c.110T[G; p.Val37Gly) in the proband and both affected sons. FPHH is not known to be associated with malignancy. Most pathogenic mutations in FPHH occur within the VTNN domain of the KITLG protein (amino acids 34-36) in contrast to observations in individuals with cancer wherein KITLG mutations may be seen in the alpha helix (amino acids 37-46). Although the malignancies in our families may be co-incidental to the mutations in KITLG, our clinicopathologic and molecular data indicate that there may be an association between FPHH and both cutaneous and internal cancers, findings that have relevance to the clinical assessment and management of these patients. Commercial support: None identified.
1428
Erythrokeratodermia variabilis (EKV, OMIM 133200) is characterized by migratory erythematous patches and hyperkeratotic plaques. EKV is a rare inherited disorder caused by the mutation in the genes encoding connexin-31 (GJB3) and connexin30.3 (GJB4), the components of gap junction, in an autosomal dominant (rarely recessive) manner. Here, we reported a first case of Japanese patient with EKV resulting from the GJB4 mutation. A 60-year-old Japanese woman had suffered from ambulant pigmented erythrokeratotic plaques without any symptoms, mainly affecting her back and shoulders, since her birth. Her hair, nail, teeth and audibility were not affected. Histopathologic examination of skin lesion showed hyperkeratosis and irregular epidermal acanthosis with slight thickening of granular layer. Both clinical and pathological findings were consistent with EKV, although there was no EKV-related family history. Direct sequence analysis of coding region in the GJB3 and GJB4 gene demonstrated that no mutations were found in GJB3, while the mutation designated as c.35G [ A was found in GJB4 . This mutation has been previously reported in Dutch population, but not in Japanese population, indicating the possibility that this site may be an interracial hotspot of the mutation in the GJB4 gene. Although topical vitamin D3 derivative (maxacalcitol) was applied to the hyperkeratotic skin lesions, it was not effective. Consequently, oral etretinate (0.4 mg/kg/day) was initiated, resulting in the complete disappearance of the skin lesions confirming several previous reports demonstrating the efficacy of oral retinoid. No recurrence was observed in the follow-up periods.
Angiokeratomas in a bathing suit distribution Lori Asztalos, MD, MS, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children’s Hospital, Chicago, IL, United States; Lisa Shen, MD, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children’s Hospital, Chicago, IL, United States; Amy Paller, MD, MS, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children’s Hospital, Chicago, IL, United States A 12-year-old boy presented with a 3-year history of small papules on the lower extremities, pain in his hands and feet, and hyperhidrosis. Family history included cerebrovascular accident (CVA) in his maternal grandmother and uncle. Physical examination showed numerous 1-3 mm dark red to violaceous nonblanching macules and hyperkeratotic dome-shaped, hyperkeratotic papules on the buttock, posterior thighs, scrotum, and lower back. Palms and soles had a livedoid pattern with distal telangiectasias. Based on the distribution and appearance of lesions, a diagnosis of Fabry disease (FD) was suspected. b-galactosidase A (GLA) level was 2.3 (14-50 nmoles/mg/hr) and the activity of GLA was 0.8 (2.8-74.1 nmol/hr/mg) in leukocytes, and 0.3 (6.2-18.6 nmol/hr/ml) in plasma. A missense mutation at G328V of the GLA gene confirmed FD and enzyme replacement therapy (ERT) was immediately started with agalisidase beta 1 mg per kg. Angiokeratomas in a bathing suit distribution, termed angiokeratoma corporis diffusum (ACD), may be the first presenting sign of FD, a rare X-linked lysosomal storage disorder with a prevalence of 1:40,000-117,000. Fabry first described ACD as small vessel aneurysms primarily occurring between the umbilicus and knees. Deficiency of GLA results in accumulation of glycosphingolipids in organs and tissues, leading to multisystem organ dysfunction including corneal and lenticular opacities, hypo/hyperhidrosis, renal and heart failure, and cerebral artery thrombosis. Pain is the most common and most debilitating symptom, described as both a ‘‘crisis’’ type agonizing pain as well as burning and tingling paresthesia. Early recognition of ACD and FD is imperative since early treatment with ERT is key in reducing organ dysfunction, improving peripheral neuropathy, decreasing pain, and improving quality of life. Annual follow-up is recommended, including evaluation of hematology, chemistry, urinary protein, creatinine clearance, audiology assessment, ophthalmologic exam, pulmonary function test, and depression assessment. Neuroimaging is important to monitor cerebrovascular involvement.
Commercial support: None identified.
Commercial support: None identified.
GENODERMATOSES 809 A Japanese case of erythrokeratodermia variabilis caused by connexin30.3 (GJB4) mutation Yumie Yoshikata, MD, The Jikei University School of Medicine, Tokyo, Japan; Munenari Itoh, MD, PhD, The Jikei University School of Medicine, Tokyo, Japan; Hidemi Nakagawa, MD, PhD, The Jikei University School of Medicine, Tokyo, Japan
MAY 2015
J AM ACAD DERMATOL
AB103
1112
Timely access to tertiary dermatologic care may reduce diagnostic delays and unnecessary healthcare services Yara Abdou, MD, University of New Mexico, School of Medicine, Albuquerque, NM, United States; Ifeoma Aguanunu, MD, MPH, University of Illinois at Chicago, College of Medicine, Chicago, IL, United States; Christine Lohse, Mayo Clinic, College of Medicine, Rochester, MN, United States; Nneka Comfere, MD, Mayo Clinic, College of Medicine, Rochester, MN, United States Skin concerns are the most common (49.7%) reason why patients visited their doctor and account for $39.3 billion in medical costs. Primary care practitioners including physician extenders with variable dermatologic expertise commonly provide dermatologic care. Increasing demand for dermatologic care in an aging population, long wait times and disparities in access are likely to further exacerbate these trends. The primary objective of this study is to assess rates of diagnostic delay, diagnostic discordance and health care utilization in referrals to a tertiary dermatology practice. A retrospective analysis of clinical and demographic characteristics and health care service utilization of 228 patients referred to the dermatology department at Mayo Clinic, Rochester (MCR) in August 2012 was performed. Patients referred to the MCR dermatology practice were predominantly women (60%), aged 55 years, had visited a provider of dermatologic services 148 miles away, and were referred by a primary care practitioner (53%). 11% of referrals had 2 or 3 prior diagnoses and 30% had seen 2 or more providers prior to their referral. 13% of referrals had $2 prior skin biopsies and 33% had $4 previous therapies. Clinical and pathologic diagnostic discordance were noted in 32% and 9% respectively, of all patients referred to the dermatology practice. Significant differences in the proportion of clinically discordant diagnoses rendered by primary care practitioners relative to dermatologists were observed (68% vs 25%; P ¼.023). Diagnostic delay of [2 years occurred in 44% of referred patients. The proportions of referring professionals from dermatology, primary care, and ‘other’ specialties with a[2 year lag in diagnosis were 48%, 37%, and 63%, respectively (P ¼.039). The correlation coefficient for the association between miles from Mayo and time lag in diagnosis was 0.37 (P \.001). The proportions of patients with clinical information that was provided, not provided, and not documented with a [2 year lag in diagnosis were 25%, 73%, and 48%, respectively (P ¼.001). Patients who received an exit diagnosis in the category of inflammatory dermatoses had the highest mean numbers of previous diagnoses (1.3), previous providers (1.8) and previous therapies (3.4), relative to those with nonmelanocytic and melanocytic proliferations. Direct and timely access to a tertiary practice for dermatologic care may facilitate accurate, timely and cost effective diagnosis.
A rare dyschromatosis possibly associated with malignancy Niharika Bansal, Solihull Hospital, Solihull, United Kingdom; Manjit Kaur, Heart of England Hospitals NHS Foundation Trust, Solihull, United Kingdom; Trevor Cole, West Midlands Regional Genetics, Birmingham, United Kingdom; Celia Moss, Birmingham Children’s Hospital, Birmingham, United Kingdom; Annette Loffeld, Solihull Hospital, Solihull, United Kingdom; Chamandeep Thind, Worcester Royal Hospital, Worcester, United Kingdom; John Lee, St John’s Institute of Dermatology, London, United Kingdom; Takuya Takeichi, St John’s Institute of Dermatology, London, United Kingdom; Marie O’Donnell, Birmingham Women’s Hospital NHSFT, Birmingham, United Kingdom; Alexis Cuell, City Hospital, Birmingham, United Kingeom; John McGrath, King’s College London, London, United Kingdom
Commercial support: None identified.
The dyschromatoses are a group of pigmentary disorders characterized by mixed hypo- and hyperpigmented lesions. Mutations in 14 genes have been reported in the inherited dyschromatoses, including the c-kit receptor ligand (KITLG). KITLG mutations lead to diverse skin phenotypes, including autosomal dominant familial progressive hyper- and hypopigmentation (FPHH), a subtype of familial progressive hyperpigmentation and dyschromatosis universalis hereditaria type 2. We describe 2 families with FPHH in whom we identified previously unreported mutations in KITLG. In addition, skin and internal malignancies were noted in both pedigrees, raising the possibility of FPHH being a new cancer-associated genodermatosis. Family 1: 3 generations of a Caucasian nonconsanguineous family presented with a progressive pigmentary disorder consisting of hypo- and hyperpigmented macules. Marked tanning and thickening of sun exposed skin was reported, changes also seen on nonesun exposed areas including palms and soles. The 62-year-old grandfather had a history of pharyngeal cancer and was found to have two primary superficial spreading melanomas on his back. DNA analysis revealed a novel germline heterozygous missense mutation (c.101C [ A: p.Thr34Asn) in KITLG in the proband, father, grandfather but not in the proband’s unaffected sister. Family 2: A 36-year-old British Caucasian woman reported progressive hyperpigmentation and dark macules with onset in early childhood. The pigmentary changes were seen in both sun-exposed and nonexposed skin, including palms and soles. She had a history of papillary thyroid cancer. 2 of her 3 sons showed similar skin changes, with increased pigmentation of skin and striking hypo- and hyperpigmented macules. DNA analysis revealed a novel germline heterozygous missense mutation in KITLG (c.110T[G; p.Val37Gly) in the proband and both affected sons. FPHH is not known to be associated with malignancy. Most pathogenic mutations in FPHH occur within the VTNN domain of the KITLG protein (amino acids 34-36) in contrast to observations in individuals with cancer wherein KITLG mutations may be seen in the alpha helix (amino acids 37-46). Although the malignancies in our families may be co-incidental to the mutations in KITLG, our clinicopathologic and molecular data indicate that there may be an association between FPHH and both cutaneous and internal cancers, findings that have relevance to the clinical assessment and management of these patients. Commercial support: None identified.
1428
Erythrokeratodermia variabilis (EKV, OMIM 133200) is characterized by migratory erythematous patches and hyperkeratotic plaques. EKV is a rare inherited disorder caused by the mutation in the genes encoding connexin-31 (GJB3) and connexin30.3 (GJB4), the components of gap junction, in an autosomal dominant (rarely recessive) manner. Here, we reported a first case of Japanese patient with EKV resulting from the GJB4 mutation. A 60-year-old Japanese woman had suffered from ambulant pigmented erythrokeratotic plaques without any symptoms, mainly affecting her back and shoulders, since her birth. Her hair, nail, teeth and audibility were not affected. Histopathologic examination of skin lesion showed hyperkeratosis and irregular epidermal acanthosis with slight thickening of granular layer. Both clinical and pathological findings were consistent with EKV, although there was no EKV-related family history. Direct sequence analysis of coding region in the GJB3 and GJB4 gene demonstrated that no mutations were found in GJB3, while the mutation designated as c.35G [ A was found in GJB4 . This mutation has been previously reported in Dutch population, but not in Japanese population, indicating the possibility that this site may be an interracial hotspot of the mutation in the GJB4 gene. Although topical vitamin D3 derivative (maxacalcitol) was applied to the hyperkeratotic skin lesions, it was not effective. Consequently, oral etretinate (0.4 mg/kg/day) was initiated, resulting in the complete disappearance of the skin lesions confirming several previous reports demonstrating the efficacy of oral retinoid. No recurrence was observed in the follow-up periods.
Angiokeratomas in a bathing suit distribution Lori Asztalos, MD, MS, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children’s Hospital, Chicago, IL, United States; Lisa Shen, MD, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children’s Hospital, Chicago, IL, United States; Amy Paller, MD, MS, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children’s Hospital, Chicago, IL, United States A 12-year-old boy presented with a 3-year history of small papules on the lower extremities, pain in his hands and feet, and hyperhidrosis. Family history included cerebrovascular accident (CVA) in his maternal grandmother and uncle. Physical examination showed numerous 1-3 mm dark red to violaceous nonblanching macules and hyperkeratotic dome-shaped, hyperkeratotic papules on the buttock, posterior thighs, scrotum, and lower back. Palms and soles had a livedoid pattern with distal telangiectasias. Based on the distribution and appearance of lesions, a diagnosis of Fabry disease (FD) was suspected. b-galactosidase A (GLA) level was 2.3 (14-50 nmoles/mg/hr) and the activity of GLA was 0.8 (2.8-74.1 nmol/hr/mg) in leukocytes, and 0.3 (6.2-18.6 nmol/hr/ml) in plasma. A missense mutation at G328V of the GLA gene confirmed FD and enzyme replacement therapy (ERT) was immediately started with agalisidase beta 1 mg per kg. Angiokeratomas in a bathing suit distribution, termed angiokeratoma corporis diffusum (ACD), may be the first presenting sign of FD, a rare X-linked lysosomal storage disorder with a prevalence of 1:40,000-117,000. Fabry first described ACD as small vessel aneurysms primarily occurring between the umbilicus and knees. Deficiency of GLA results in accumulation of glycosphingolipids in organs and tissues, leading to multisystem organ dysfunction including corneal and lenticular opacities, hypo/hyperhidrosis, renal and heart failure, and cerebral artery thrombosis. Pain is the most common and most debilitating symptom, described as both a ‘‘crisis’’ type agonizing pain as well as burning and tingling paresthesia. Early recognition of ACD and FD is imperative since early treatment with ERT is key in reducing organ dysfunction, improving peripheral neuropathy, decreasing pain, and improving quality of life. Annual follow-up is recommended, including evaluation of hematology, chemistry, urinary protein, creatinine clearance, audiology assessment, ophthalmologic exam, pulmonary function test, and depression assessment. Neuroimaging is important to monitor cerebrovascular involvement.
Commercial support: None identified.
Commercial support: None identified.
GENODERMATOSES 809 A Japanese case of erythrokeratodermia variabilis caused by connexin30.3 (GJB4) mutation Yumie Yoshikata, MD, The Jikei University School of Medicine, Tokyo, Japan; Munenari Itoh, MD, PhD, The Jikei University School of Medicine, Tokyo, Japan; Hidemi Nakagawa, MD, PhD, The Jikei University School of Medicine, Tokyo, Japan
MAY 2015
J AM ACAD DERMATOL
AB103