J AM ACAD DERMATOL
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about the need to carry out proper and strict photoprotection to avoid such photosensitivity reactions. Dolores Caro-Gutie rrez, MD, Maria Ux ua Florist an Muruz abal, MD, Enrique G omez de la Fuente, MD, Ana Pampın Franco, MD, and Jose Luis L opez Estebaranz, MD Department of Dermatology, Hospital Universitario Fundaci on Alcorc on, Madrid, Spain Funding sources: None. Conflicts of interest: None declared. Correspondence to: Dolores Caro-Gutie rrez, MD, Hospital Universitario Fundaci on Alcorcon, Calle Budapest 1, 28922, Alcorc on, Madrid, Espa~ na E-mail: [email protected] REFERENCES 1. Campbell MJ, Seib CD, Gosnell J. Vandetanib and the management of advanced medullary thyroid cancer. Curr Opin Oncol 2013;25:39-43. 2. Giacchero D, Ramacciotti C, Arnault JP, Brassard M, Baudin E, Maksimovic L, et al. A new spectrum of skin toxic effects associated with the multikinase inhibitor vandetanib. Arch Dermatol 2012;148:1418-20. 3. Yoon J, Oh CW, Kim CY. Stevens-Johnson syndrome induced by vandetanib. Ann Dermatol 2011;23(Suppl):S343-5. 4. Rodrıguez-Pazos L, G omez-Bernal S, Rodrıguez-Granados MT, Toribio J. Photodistributed erythema multiforme. Actas Dermosifiliogr 2013;104:645-53. http://dx.doi.org/10.1016/j.jaad.2014.05.003
Repigmentation of hair associated with melanoma in situ of scalp To the Editor: An 88-year-old woman presented with a slowly darkening patch of previously white hair on her superior scalp (Fig 1). On physical examination, she had an underlying 6.5- 3 3-cm scaly, irregularly pigmented plaque on her superior scalp. A shave biopsy of the plaque showed actinic keratosis as well as melanoma in situ, lentigo maligna type, extending along the dermoepidermal junction and down the hair follicle. Further scouting punch biopsies were performed to identify the extent of disease, including peripheral areas that contained pigmented hair shafts despite clinically normalappearing epidermis. Histopathology of these repeat biopsies showed multiple foci of actinic keratosis and a few areas with atypical melanocytes suspicious for, but not diagnostic of, melanoma in situ. Interestingly, there were 2 areas that showed pigmented hair shafts and hair bulbs with histopathologically normal dendritic melanocytes
Fig 1. Repigmented hair overlying melanoma in situ of scalp. Slowly darkening patch of previously white hair on superior scalp.
and no evidence of overlying melanoma in situ or actinic keratosis. Normal hair follicle pigmentation and physiologic graying are under complex genetic, metabolic, enzymatic, and signaling control.1,2 The mechanism responsible for our patient’s follicular repigmentation is unclear, although we believe it is most likely due to her overlying melanoma in situ or chronic sun damage. It is unlikely due to medication use because the patient was not taking any medications previously associated with hair repigmentation. Because the dendritic melanocytes in our patient’s hair bulb appeared normal on histologic examination, the follicular melanocytes were more likely stimulated to produce melanin by external signals rather than by a direct effect of melanoma cells repopulating the hair bulb. These signals could be from the lentigo maligna cells themselves or by changes in the microenvironment. To our knowledge, there is 1 previously reported case of hair repigmentation associated with lentigo maligna, which also showed no invasion of the hair follicles by the melanoma cells.3 In that case, the patient’s hair grew back gray after the melanoma was treated by radiotherapy, suggesting that normal hair physiology was restored once the malignant cells were removed. If these signals arise from the lentigo maligna, it would be interesting to clarify how the neoplastic cells could upregulate melanogenesis in nearby normal follicular melanocytes, and which of the numerous cytokines, enzymes, and metabolites required for normal pigmentation were involved in the process. The repigmentation could also be related to chronic sun exposure and actinic damage, as evidenced by the presence of actinic keratoses. In particular, chronic sun exposure causes upregulation of many molecules associated with melanogenesis, including stem cell
J AM ACAD DERMATOL VOLUME 71, NUMBER 4
factor, alpha melanocyte stimulating hormone, c-Kit receptor, and tyrosinase.1,4 Whereas graying is considered part of the normal aging process, hair repigmentation is rare and may even indicate an underlying pathology such as melanoma in situ, as in this case. Now that there have been at least 2 reported cases of hair repigmentation associated with lentigo maligna, this clinical sign should alert the physician to a potential underlying cutaneous malignancy. More research is warranted to further investigate the mechanisms of repigmentation. It would be of great clinical significance if these pathways could be understood and used to treat the underlying malignancy or even to safely repigment white and graying hair for cosmetic purposes. Jeffrey B. Tiger, MD,a,b Kaiane A. Habeshian, BS,c Dorothea T. Barton, MD,a and Jeoffry B. Brennick, MDa Dartmouth-Hitchcock Medical Center,a Lebanon, New Hampshire; Roger Williams Medical Center,b Providence, Rhode Island; Geisel School of Medicine at Dartmouth,c Hanover, New Hampshire Dr Tiger is currently affiliated with Lahey Hospital & Medical Center, Burlington, Massachusetts This case was presented by Jeffrey B. Tiger, MD, the corresponding author, at the Gross and Microscopic Symposium at the American Academy of Dermatology’s 2013 Annual Meeting, Saturday, March 2, 2013. Funding sources: None. Conflicts of interest: None declared. Correspondence to: Jeffrey B. Tiger, MD, 1141 Beacon Street, Brookline, MA 02446 E-mail: [email protected]
REFERENCES 1. Slominski A, Wortsman J, Plonka PM, Schallreuter KU, Paus R, Tobin DJ. Hair follicle pigmentation. J Invest Dermatol 2005; 124:13-21. 2. Steingrimsson E, Copeland NG, Jenkins NA. Melanocyte stem cell maintenance and hair graying. Cell 2005;121:9-12. 3. Dummer R. Clinical picture: hair repigmentation in lentigo maligna. Lancet 2001;357(9256):598. 4. Hachiya A, Kobayashi A, Ohuchi A, Takema Y, Imokawa G. The paracrine role of stem cell factor/c-kit signaling in the activation of human melanocytes in ultraviolet-B-induced pigmentation. J Invest Dermatol 2001;116:578-86. http://dx.doi.org/10.1016/j.jaad.2014.05.019
Letters e145
Acute postoperative pyoderma gangrenosum case and review of literature identifying chest wall predominance and no recurrence following skin grafts To the Editor: Acute postoperative pyoderma gangrenosum (PPG) is a rare ulcerative cutaneous disease often misdiagnosed as a postoperative wound infection. The etiology of PG is unknown, although abnormal neutrophil chemotaxis has been implicated.1 Most recently, a novel mutation in PSTPIP1, which encodes a cytoskeletal adaptor protein that inhibits macrophage function, was identified in a patient with aggressive PG. The mutated protein induced filopodia formation in macrophages and led to increased matrix degradation.2 We present a patient seen at our institution and key findings from analysis of 90 episodes of PPG in 87 patients from the literature. A 30-year-old woman with a history of hypogammaglobulinemia presented with bilateral breast wound breakdown 6 days after breast reduction surgery. She was febrile with a white blood cell count of 18.8 (103/L). Cultures from the right breast wounds were positive for Pseudomonas aeruginosa. She was treated with multiple antibiotics and repeated surgical debridement without improvement. On examination, there was necrotic eschar overlying bilateral breast ulcers with surrounding superficial bullae and intense erythema. A perilesional biopsy demonstrated a dense neutrophilic dermal infiltrate without evidence of vasculitis or infection; special stains for bacteria were negative. PPG was diagnosed and the patient was started on methylprednisolone 60 mg 4 times daily and cyclosporine 300 mg daily with improvement noted within 48 hours. The patient was discharged on a prednisone taper and cyclosporine 300 mg daily. Complete healing occurred in 3 months. The patient elected to undergo bilateral transverse rectus abdominis myocutaneous flap breast reconstruction surgery 6 months after her initial surgery. Preoperatively, she continued cyclosporine 300 mg daily. Again, diffuse wound breakdown occurred 5 days postoperatively. Cyclosporine was continued and the patient was started on methylprednisolone 30 mg every 6 hours with rapid improvement and healing 4 months later. In review of 76 published articles, 106 PPG cases were identified. Of these, 87 patients undergoing 90 procedures met criteria for developing wound breakdown within 21 days following surgery, consistent with acute PPG (Table I), and were included in the analysis. PPG was reported following surgery involving the chest wall in 42 cases (47%) (Fig 1).
e144 Letters
OCTOBER 2014
about the need to carry out proper and strict photoprotection to avoid such photosensitivity reactions. Dolores Caro-Gutie rrez, MD, Maria Ux ua Florist an Muruz abal, MD, Enrique G omez de la Fuente, MD, Ana Pampın Franco, MD, and Jose Luis L opez Estebaranz, MD Department of Dermatology, Hospital Universitario Fundaci on Alcorc on, Madrid, Spain Funding sources: None. Conflicts of interest: None declared. Correspondence to: Dolores Caro-Gutie rrez, MD, Hospital Universitario Fundaci on Alcorcon, Calle Budapest 1, 28922, Alcorc on, Madrid, Espa~ na E-mail: [email protected] REFERENCES 1. Campbell MJ, Seib CD, Gosnell J. Vandetanib and the management of advanced medullary thyroid cancer. Curr Opin Oncol 2013;25:39-43. 2. Giacchero D, Ramacciotti C, Arnault JP, Brassard M, Baudin E, Maksimovic L, et al. A new spectrum of skin toxic effects associated with the multikinase inhibitor vandetanib. Arch Dermatol 2012;148:1418-20. 3. Yoon J, Oh CW, Kim CY. Stevens-Johnson syndrome induced by vandetanib. Ann Dermatol 2011;23(Suppl):S343-5. 4. Rodrıguez-Pazos L, G omez-Bernal S, Rodrıguez-Granados MT, Toribio J. Photodistributed erythema multiforme. Actas Dermosifiliogr 2013;104:645-53. http://dx.doi.org/10.1016/j.jaad.2014.05.003
Repigmentation of hair associated with melanoma in situ of scalp To the Editor: An 88-year-old woman presented with a slowly darkening patch of previously white hair on her superior scalp (Fig 1). On physical examination, she had an underlying 6.5- 3 3-cm scaly, irregularly pigmented plaque on her superior scalp. A shave biopsy of the plaque showed actinic keratosis as well as melanoma in situ, lentigo maligna type, extending along the dermoepidermal junction and down the hair follicle. Further scouting punch biopsies were performed to identify the extent of disease, including peripheral areas that contained pigmented hair shafts despite clinically normalappearing epidermis. Histopathology of these repeat biopsies showed multiple foci of actinic keratosis and a few areas with atypical melanocytes suspicious for, but not diagnostic of, melanoma in situ. Interestingly, there were 2 areas that showed pigmented hair shafts and hair bulbs with histopathologically normal dendritic melanocytes
Fig 1. Repigmented hair overlying melanoma in situ of scalp. Slowly darkening patch of previously white hair on superior scalp.
and no evidence of overlying melanoma in situ or actinic keratosis. Normal hair follicle pigmentation and physiologic graying are under complex genetic, metabolic, enzymatic, and signaling control.1,2 The mechanism responsible for our patient’s follicular repigmentation is unclear, although we believe it is most likely due to her overlying melanoma in situ or chronic sun damage. It is unlikely due to medication use because the patient was not taking any medications previously associated with hair repigmentation. Because the dendritic melanocytes in our patient’s hair bulb appeared normal on histologic examination, the follicular melanocytes were more likely stimulated to produce melanin by external signals rather than by a direct effect of melanoma cells repopulating the hair bulb. These signals could be from the lentigo maligna cells themselves or by changes in the microenvironment. To our knowledge, there is 1 previously reported case of hair repigmentation associated with lentigo maligna, which also showed no invasion of the hair follicles by the melanoma cells.3 In that case, the patient’s hair grew back gray after the melanoma was treated by radiotherapy, suggesting that normal hair physiology was restored once the malignant cells were removed. If these signals arise from the lentigo maligna, it would be interesting to clarify how the neoplastic cells could upregulate melanogenesis in nearby normal follicular melanocytes, and which of the numerous cytokines, enzymes, and metabolites required for normal pigmentation were involved in the process. The repigmentation could also be related to chronic sun exposure and actinic damage, as evidenced by the presence of actinic keratoses. In particular, chronic sun exposure causes upregulation of many molecules associated with melanogenesis, including stem cell
J AM ACAD DERMATOL VOLUME 71, NUMBER 4
factor, alpha melanocyte stimulating hormone, c-Kit receptor, and tyrosinase.1,4 Whereas graying is considered part of the normal aging process, hair repigmentation is rare and may even indicate an underlying pathology such as melanoma in situ, as in this case. Now that there have been at least 2 reported cases of hair repigmentation associated with lentigo maligna, this clinical sign should alert the physician to a potential underlying cutaneous malignancy. More research is warranted to further investigate the mechanisms of repigmentation. It would be of great clinical significance if these pathways could be understood and used to treat the underlying malignancy or even to safely repigment white and graying hair for cosmetic purposes. Jeffrey B. Tiger, MD,a,b Kaiane A. Habeshian, BS,c Dorothea T. Barton, MD,a and Jeoffry B. Brennick, MDa Dartmouth-Hitchcock Medical Center,a Lebanon, New Hampshire; Roger Williams Medical Center,b Providence, Rhode Island; Geisel School of Medicine at Dartmouth,c Hanover, New Hampshire Dr Tiger is currently affiliated with Lahey Hospital & Medical Center, Burlington, Massachusetts This case was presented by Jeffrey B. Tiger, MD, the corresponding author, at the Gross and Microscopic Symposium at the American Academy of Dermatology’s 2013 Annual Meeting, Saturday, March 2, 2013. Funding sources: None. Conflicts of interest: None declared. Correspondence to: Jeffrey B. Tiger, MD, 1141 Beacon Street, Brookline, MA 02446 E-mail: [email protected]
REFERENCES 1. Slominski A, Wortsman J, Plonka PM, Schallreuter KU, Paus R, Tobin DJ. Hair follicle pigmentation. J Invest Dermatol 2005; 124:13-21. 2. Steingrimsson E, Copeland NG, Jenkins NA. Melanocyte stem cell maintenance and hair graying. Cell 2005;121:9-12. 3. Dummer R. Clinical picture: hair repigmentation in lentigo maligna. Lancet 2001;357(9256):598. 4. Hachiya A, Kobayashi A, Ohuchi A, Takema Y, Imokawa G. The paracrine role of stem cell factor/c-kit signaling in the activation of human melanocytes in ultraviolet-B-induced pigmentation. J Invest Dermatol 2001;116:578-86. http://dx.doi.org/10.1016/j.jaad.2014.05.019
Letters e145
Acute postoperative pyoderma gangrenosum case and review of literature identifying chest wall predominance and no recurrence following skin grafts To the Editor: Acute postoperative pyoderma gangrenosum (PPG) is a rare ulcerative cutaneous disease often misdiagnosed as a postoperative wound infection. The etiology of PG is unknown, although abnormal neutrophil chemotaxis has been implicated.1 Most recently, a novel mutation in PSTPIP1, which encodes a cytoskeletal adaptor protein that inhibits macrophage function, was identified in a patient with aggressive PG. The mutated protein induced filopodia formation in macrophages and led to increased matrix degradation.2 We present a patient seen at our institution and key findings from analysis of 90 episodes of PPG in 87 patients from the literature. A 30-year-old woman with a history of hypogammaglobulinemia presented with bilateral breast wound breakdown 6 days after breast reduction surgery. She was febrile with a white blood cell count of 18.8 (103/L). Cultures from the right breast wounds were positive for Pseudomonas aeruginosa. She was treated with multiple antibiotics and repeated surgical debridement without improvement. On examination, there was necrotic eschar overlying bilateral breast ulcers with surrounding superficial bullae and intense erythema. A perilesional biopsy demonstrated a dense neutrophilic dermal infiltrate without evidence of vasculitis or infection; special stains for bacteria were negative. PPG was diagnosed and the patient was started on methylprednisolone 60 mg 4 times daily and cyclosporine 300 mg daily with improvement noted within 48 hours. The patient was discharged on a prednisone taper and cyclosporine 300 mg daily. Complete healing occurred in 3 months. The patient elected to undergo bilateral transverse rectus abdominis myocutaneous flap breast reconstruction surgery 6 months after her initial surgery. Preoperatively, she continued cyclosporine 300 mg daily. Again, diffuse wound breakdown occurred 5 days postoperatively. Cyclosporine was continued and the patient was started on methylprednisolone 30 mg every 6 hours with rapid improvement and healing 4 months later. In review of 76 published articles, 106 PPG cases were identified. Of these, 87 patients undergoing 90 procedures met criteria for developing wound breakdown within 21 days following surgery, consistent with acute PPG (Table I), and were included in the analysis. PPG was reported following surgery involving the chest wall in 42 cases (47%) (Fig 1).
