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Narrowband ultraviolet B phototherapy influences serum folate levels in patients with vitiligo
710 Letters
J AM ACAD DERMATOL APRIL 2010
Narrowband ultraviolet B phototherapy influences serum folate levels in patients with vitiligo To the Editor: We read with interest the article by Rose et al1 in the August 2009 issue of the Journal. Ultraviolet B light phototherapy (UVB) is generally considered the safest form of systemic psoriasis therapy in pregnancy. We commend the authors for creating a study to examine the photodegradation of serum folate after exposure to narrowband UVB (nbUVB), given that folate deficiency in the first trimester of pregnancy could predispose to the development of neural tube defects. Interestingly, a similar study had been performed in 2006 by Shaheen et al2 that revealed very different results. A comparison of the two studies is provided in Table I. Shaheen et al’s study consisted of vitiligo patients, and Rose et al’s study consisted of psoriasis patients. There was a statistically significant drop in folate serum levels after 36 exposures of nbUVB, in contrast to Rose et al’s findings that indicate no change in the levels after 18 exposures. Shaheen et al’s study did not measure red cell folate levels, so it is only possible to compare serum folate levels. Importantly, in both studies, there were no patients who attained folate deficiency levels (\3.7 ng/mL). The primary difference between the two studies appears to be that Shaheen et al’s study patients received higher doses of phototherapy over a longer period of time. Weaknesses in Rose et al’s study, when compared to Shaheen et al’s study, are as follows: (1) There was no mention of whether blood samples were protected from light before the measurement of folate to limit in vitro alterations of folate levels; (2) There was no control group; (3) The number of phototherapy sessions in Rose et al’s study was half that of Shaheen et al’s study; and (4) Cumulative UVB dose was not reported, but was likely much less than half that of Shaheen et al’s study. In Shaheen et al’s study, the cumulative UVB dose was reported as 75.95 6 3.67 J/cm2 (range, 70.7979.88), which is an average treatment dose of 2.1 J/cm2 per patient. In Rose et al’s study, patients’ doses were increased at each visit to a maximum of 2.3 J/cm2. The average treatment dose of Shaheen et al’s study is close to the maximum allowed in Rose et al’s study, which implies that the irradiance at each treatment was likely much less. The authors correctly state that there have been no studies to indicate whether or not ultraviolet light
Table I. Comparison of two narrowband ultraviolet B folic acid degradation studies
Condition
Patients (study vs control)
Vitiligo* 20 S/20 C 35 S Psoriasisy
Exposure Folate levels Folate levels after exposure baseline (no. of (ng/L) (ng/mL) treatments)
36 18
8.1 6 2.6 6.3 6 3.6
5.9 6 1.5 6.4 6 3.3
C, Control; S, study. *Shaheen et al.2 y Rose et al.1
therapy increases a patient’s risk for neural tube defects. There are also no studies that indicate appropriate folate supplementation during phototherapy. Folic acid supplementation in a normal pregnancy ranges from 0.4 to 1 mg a day. High risk patients may require up to 5 mg, but it is important to rule out vitamin B12 deficiency if a patient is supplementing with more than 1 mg/day,3 because vitamin B12 deficiency and high serum folate are associated with increased risk of cognitive impairment and anemia.4 Because the critical period of organogenesis, extending from 2 weeks before to 6 weeks after the missed menstrual period, can be over before a patient realizes that she is pregnant, we recommend that dermatologists discuss folic acid supplementation with their female patients of childbearing age considering phototherapy. Jenny E. Murase, MD,a,b John Y. M. Koo, MD,a and Timothy G. Berger, MDa Departments of Dermatology at the University of California, San Francisco,a San Francisco, and the Palo Alto Foundation Medical Group,b Mountain View, California. Funding sources: None. Conflicts of interest: None declared. Reprints requests and correspondence: Jenny E. Murase, MD, Department of Dermatology, Palo Alto Foundation Medical Group, 701 E El Camino Real (31-104), Mountain View, CA 94040 E-mail: [email protected] REFERENCES 1. Rose RF, Batchelor RJ, Turner D, Goulden V. Narrowband ultraviolet B phototherapy does not influence serum and red cell folate levels in patients with psoriasis. J Am Acad Dermatol 2009;61:259-62. 2. Shaheen MA, Abdel Fattah NS, El-Borhamy MI. Analysis of serum folate levels after narrow band UVB exposure. Egypt Dermatol Online J 2006;2:13. 3. Wilson RD, Davies G, De´silets V, Reid GJ, Summers A, Wyatt P, et al. The use of folic acid for the prevention of neural tube
Letters 711
J AM ACAD DERMATOL VOLUME 62, NUMBER 4
defects and other congenital abnormalities. J Obstet Gynaecol Can 2003;25:959-73. 4. Selhub J, Morris MS, Jacques PF. In vitamin B12 deficiency, higher serum folate is associated with increased total
CASE Myxoinflammatory fibroblastic sarcoma on the thigh To the Editor: Myxoinflammatory fibroblastic sarcoma (MIFS) is a slow growing, low grade tumor reported as a soft tissue tumor affecting the distal extremities. It was first described in 1998 by MeisKindblom and Kindblom1 and Montgomery et al.2 Although it was described by different names—acral MIFS and inflammatory myxohyaline tumor of distal extremities with virocyte or Reed-Sternbergelike cells—it described the same entity of histologic features.1,2 The reported histologic similarities included numerous inflammatory cells (plasma cells, granulocytes, eosinophils, and lymphocytes), fibrosis, and scattered, large, bizarre tumor cells resembling Reed-Sternbergelike cells in an abundant myxoid extracellular matrix. Clinically, it is described in all age groups (4-91 yrs of age),1-6 occurs approximately equally among males and females,1-3 and commonly presents as a painless subcutaneous mass located in the distal extremities.1-5 In 2002, Jurcic et al4 reported 3 cases not located in the acral extremities, suggesting that the term ‘‘acral’’ was misleading when describing the tumor. A 56-year-old female patient presented to our dermatology clinic with no significant medical history with a chief complaint of an 8-week history of a painful mass located on the right proximal lateral thigh. The patient noted that the mass had progressively increased in size over the past 8 weeks. Clinical examination revealed a firm 1.5-cm subcutaneous nodule, which was thought to be an epithelial inclusion cyst or lipoma. A histopathological examination revealed a lesion with an almost biphasic appearance. There were solidly cellular areas with a fibrovascular appearance transitioning into foci of tumor with a very copious myxoid matrix containing thin walled blood vessels (Fig 1). Large Reed-Sternbergelike cells with vesicular nuclei containing prominent nucleoli were present in the more cellular areas (Fig 2, A). Scattered mitotic figures and eosinophils were also present (Fig 2, B). The lateral margins showed
homocysteine and methylmalonic acid concentrations. Proc Natl Acad Sci U S A 2007;104:19995-20000. doi:10.1016/j.jaad.2009.10.006
LETTERS
Fig 1. Appearance at low power showing a myxoid matrix surrounded by bands of fibrosis.
evidence of tumor, so the patient was referred to a general surgeon for reexcision. She has had four additional excisions because of positive margins, and is currently being evaluated by a radiation oncologist for further treatment. There have been two reported cases of myxoinflammatory fibroblastic sarcoma located on the thigh. The first case, by Montgomery et al,2 reported a patient treated with wide local excision with no recurrence on follow-up. The second case was reported by Jurcic et al4 in 2002 in an 87-year-old male patient who had the tumor excised. The tumor recurred 5 years later and was reexcised at that time with no evidence of disease at 1-year follow-up. Most patients are treated with local wide resection because recurrence is common ([50%),3 with the earliest reported recurrence at 3 months after the first excision. It has been reported to have a significant risk of local recurrence with a low rate of metastasis,6 which can be distinguished from myxofibrosarcoma, also known as myxoid malignant fibrous histiocytoma, which has a high rate of metastasis. The latter also has cells that demonstrate greater nuclear atypia and enlargement and pleomorphism but lack the Reed-Sternbergelike cells and have a lower number of inflammatory cells.2 The importance of distinguishing histologically between the two entities allows an accurate diagnosis and treatment for the patient.
J AM ACAD DERMATOL APRIL 2010
Narrowband ultraviolet B phototherapy influences serum folate levels in patients with vitiligo To the Editor: We read with interest the article by Rose et al1 in the August 2009 issue of the Journal. Ultraviolet B light phototherapy (UVB) is generally considered the safest form of systemic psoriasis therapy in pregnancy. We commend the authors for creating a study to examine the photodegradation of serum folate after exposure to narrowband UVB (nbUVB), given that folate deficiency in the first trimester of pregnancy could predispose to the development of neural tube defects. Interestingly, a similar study had been performed in 2006 by Shaheen et al2 that revealed very different results. A comparison of the two studies is provided in Table I. Shaheen et al’s study consisted of vitiligo patients, and Rose et al’s study consisted of psoriasis patients. There was a statistically significant drop in folate serum levels after 36 exposures of nbUVB, in contrast to Rose et al’s findings that indicate no change in the levels after 18 exposures. Shaheen et al’s study did not measure red cell folate levels, so it is only possible to compare serum folate levels. Importantly, in both studies, there were no patients who attained folate deficiency levels (\3.7 ng/mL). The primary difference between the two studies appears to be that Shaheen et al’s study patients received higher doses of phototherapy over a longer period of time. Weaknesses in Rose et al’s study, when compared to Shaheen et al’s study, are as follows: (1) There was no mention of whether blood samples were protected from light before the measurement of folate to limit in vitro alterations of folate levels; (2) There was no control group; (3) The number of phototherapy sessions in Rose et al’s study was half that of Shaheen et al’s study; and (4) Cumulative UVB dose was not reported, but was likely much less than half that of Shaheen et al’s study. In Shaheen et al’s study, the cumulative UVB dose was reported as 75.95 6 3.67 J/cm2 (range, 70.7979.88), which is an average treatment dose of 2.1 J/cm2 per patient. In Rose et al’s study, patients’ doses were increased at each visit to a maximum of 2.3 J/cm2. The average treatment dose of Shaheen et al’s study is close to the maximum allowed in Rose et al’s study, which implies that the irradiance at each treatment was likely much less. The authors correctly state that there have been no studies to indicate whether or not ultraviolet light
Table I. Comparison of two narrowband ultraviolet B folic acid degradation studies
Condition
Patients (study vs control)
Vitiligo* 20 S/20 C 35 S Psoriasisy
Exposure Folate levels Folate levels after exposure baseline (no. of (ng/L) (ng/mL) treatments)
36 18
8.1 6 2.6 6.3 6 3.6
5.9 6 1.5 6.4 6 3.3
C, Control; S, study. *Shaheen et al.2 y Rose et al.1
therapy increases a patient’s risk for neural tube defects. There are also no studies that indicate appropriate folate supplementation during phototherapy. Folic acid supplementation in a normal pregnancy ranges from 0.4 to 1 mg a day. High risk patients may require up to 5 mg, but it is important to rule out vitamin B12 deficiency if a patient is supplementing with more than 1 mg/day,3 because vitamin B12 deficiency and high serum folate are associated with increased risk of cognitive impairment and anemia.4 Because the critical period of organogenesis, extending from 2 weeks before to 6 weeks after the missed menstrual period, can be over before a patient realizes that she is pregnant, we recommend that dermatologists discuss folic acid supplementation with their female patients of childbearing age considering phototherapy. Jenny E. Murase, MD,a,b John Y. M. Koo, MD,a and Timothy G. Berger, MDa Departments of Dermatology at the University of California, San Francisco,a San Francisco, and the Palo Alto Foundation Medical Group,b Mountain View, California. Funding sources: None. Conflicts of interest: None declared. Reprints requests and correspondence: Jenny E. Murase, MD, Department of Dermatology, Palo Alto Foundation Medical Group, 701 E El Camino Real (31-104), Mountain View, CA 94040 E-mail: [email protected] REFERENCES 1. Rose RF, Batchelor RJ, Turner D, Goulden V. Narrowband ultraviolet B phototherapy does not influence serum and red cell folate levels in patients with psoriasis. J Am Acad Dermatol 2009;61:259-62. 2. Shaheen MA, Abdel Fattah NS, El-Borhamy MI. Analysis of serum folate levels after narrow band UVB exposure. Egypt Dermatol Online J 2006;2:13. 3. Wilson RD, Davies G, De´silets V, Reid GJ, Summers A, Wyatt P, et al. The use of folic acid for the prevention of neural tube
Letters 711
J AM ACAD DERMATOL VOLUME 62, NUMBER 4
defects and other congenital abnormalities. J Obstet Gynaecol Can 2003;25:959-73. 4. Selhub J, Morris MS, Jacques PF. In vitamin B12 deficiency, higher serum folate is associated with increased total
CASE Myxoinflammatory fibroblastic sarcoma on the thigh To the Editor: Myxoinflammatory fibroblastic sarcoma (MIFS) is a slow growing, low grade tumor reported as a soft tissue tumor affecting the distal extremities. It was first described in 1998 by MeisKindblom and Kindblom1 and Montgomery et al.2 Although it was described by different names—acral MIFS and inflammatory myxohyaline tumor of distal extremities with virocyte or Reed-Sternbergelike cells—it described the same entity of histologic features.1,2 The reported histologic similarities included numerous inflammatory cells (plasma cells, granulocytes, eosinophils, and lymphocytes), fibrosis, and scattered, large, bizarre tumor cells resembling Reed-Sternbergelike cells in an abundant myxoid extracellular matrix. Clinically, it is described in all age groups (4-91 yrs of age),1-6 occurs approximately equally among males and females,1-3 and commonly presents as a painless subcutaneous mass located in the distal extremities.1-5 In 2002, Jurcic et al4 reported 3 cases not located in the acral extremities, suggesting that the term ‘‘acral’’ was misleading when describing the tumor. A 56-year-old female patient presented to our dermatology clinic with no significant medical history with a chief complaint of an 8-week history of a painful mass located on the right proximal lateral thigh. The patient noted that the mass had progressively increased in size over the past 8 weeks. Clinical examination revealed a firm 1.5-cm subcutaneous nodule, which was thought to be an epithelial inclusion cyst or lipoma. A histopathological examination revealed a lesion with an almost biphasic appearance. There were solidly cellular areas with a fibrovascular appearance transitioning into foci of tumor with a very copious myxoid matrix containing thin walled blood vessels (Fig 1). Large Reed-Sternbergelike cells with vesicular nuclei containing prominent nucleoli were present in the more cellular areas (Fig 2, A). Scattered mitotic figures and eosinophils were also present (Fig 2, B). The lateral margins showed
homocysteine and methylmalonic acid concentrations. Proc Natl Acad Sci U S A 2007;104:19995-20000. doi:10.1016/j.jaad.2009.10.006
LETTERS
Fig 1. Appearance at low power showing a myxoid matrix surrounded by bands of fibrosis.
evidence of tumor, so the patient was referred to a general surgeon for reexcision. She has had four additional excisions because of positive margins, and is currently being evaluated by a radiation oncologist for further treatment. There have been two reported cases of myxoinflammatory fibroblastic sarcoma located on the thigh. The first case, by Montgomery et al,2 reported a patient treated with wide local excision with no recurrence on follow-up. The second case was reported by Jurcic et al4 in 2002 in an 87-year-old male patient who had the tumor excised. The tumor recurred 5 years later and was reexcised at that time with no evidence of disease at 1-year follow-up. Most patients are treated with local wide resection because recurrence is common ([50%),3 with the earliest reported recurrence at 3 months after the first excision. It has been reported to have a significant risk of local recurrence with a low rate of metastasis,6 which can be distinguished from myxofibrosarcoma, also known as myxoid malignant fibrous histiocytoma, which has a high rate of metastasis. The latter also has cells that demonstrate greater nuclear atypia and enlargement and pleomorphism but lack the Reed-Sternbergelike cells and have a lower number of inflammatory cells.2 The importance of distinguishing histologically between the two entities allows an accurate diagnosis and treatment for the patient.