Cicatricial Alopecia Secondary to Radiation Therapy: Case Report and Review of the Literature
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Cicatricial Alopecia Secondary to Radiation Therapy: Case Report and Review of the Literature Gregg A. Severs, DO; Thomas Griffin, MD; Maria Werner-Wasik, MD Cicatricial or scarring alopecia represents perma- icatricial or scarring alopecia represents nent destruction of the hair follicle, histopatholog- permanent destruction of the hair follicle. ically showing a decreased number of follicular C Clinically, depending on the cause, there is units leaving streamers of fibrosis or hyalinization effacement of follicular orifices in a patchy or dif- of surrounding collagen. High-dose radiation fuse distribution. A biopsy is confirmatory, show- therapy (RT) used for treating intracranial malig- ing a decreased number of follicular units leaving nancy can permanently destroy hair follicles, streamers of fibrosis or hyalinization of surround- resulting in permanent alopecia. Typically, there ing collagen.1 There are several well-recognized also is clinical scarring of the skin with dermal causes of secondary cicatricial alopecia, such as fibrosis. We report a case of radiation-induced infection, inflammatory processes, and physical cicatricial alopecia confirmed by histopathol- sources (eg, radiation, burns).2 Alopecia and loss ogy, without obvious clinical scarring or dermal of sebaceous and sweat glands in radiated sites is a fibrosis. This lack of fibrosis made our patient a dose-dependent phenomenon that can be tempo- good candidate for hair transplantation. The clini- rary or permanent.1 Patients usually recover from copathologic presentation in this case could be the hair loss (anagen arrest) associated with radia- related to the method of RT employed in treating tion therapy (RT), but a sufficiently high dose of our patient’s brain tumor. A literature review of radiation used for treating intracranial malignancy radiation-induced cicatricial alopecia, as well as can permanently destroy hair follicles.3 a brief discussion of the current radiation methods High-dose RT, resulting in permanent alopecia, used in the treatment of intracranial malignancy, typically leads to clinical scarring of the skin with is presented. We believe that because most ana- dermal fibrosis. We report a case of radiation- gen follicles are approximately 4 mm deep in the induced cicatricial alopecia confirmed by histo- skin, if the dose of radiation superficial to a depth pathology, without obvious clinical scarring or of 5 mm is kept under 16 Gy, which is the approxi- dermal fibrosis. This lack of fibrosis made our pa- mate lethal dose for hair follicles, the incidence tient a good candidate for hair transplantation. of radiation-induced cicatricial alopecia could be The clinicopathologic presentation in this case avoided or markedly decreased. could be related to the method of RT employed Cutis. 2008;81:147-153. in treating our patient’s brain tumor. Because of this atypical clinical appearance and the paucity of reports documenting the histopathologic features of radiation-induced cicatricial alopecia, we present the following case and review of the literature. Accepted for publication March 15, 2007. Dr. Severs is in private practice, Scranton, Pennsylvania. Case Report Dr. Griffin is from the Department of Dermatology, Drexel A World Health Organization grade III astrocy- University, Philadelphia, Pennsylvania. Dr. Werner-Wasik is toma (anaplastic astrocytoma) was diagnosed in from the Department of Radiation Oncology, Jefferson a 25-year-old woman in July 2001. The lesion Medical College, Philadelphia. The authors report no conflict of interest. was surgically removed and the craniotomy was Correspondence: Gregg A. Severs, DO, 327 N Washington Ave, bridged with a titanium plate. She then received Suite 200, Scranton, PA 18503 ([email protected]). 3-dimensional conformal radiation therapy (3D-CRT) VOLUME 81, FEBRUARY 2008 147 Cicatricial Alopecia Radiation Isodose Distributiona Radiation Line Tissue Tissue Dose, % Color Dose, Gy Depth 93 Cyclamen 60.0 1.32 cm 90 Green 58.0 1.00 cm 80 Purple 51.6 0.7 cm 50 Yellow 32.2 0.4 cm 30 Pink 19.35b 0.1–0.2 cmb aThe tumor is represented with a red line. bThe doses at a depth of 0.1 to 0.2 cm are notoriously difficult to assess precisely, so this is an estimate. Figure 1. The distribution of radiation therapy doses at depths of particular isodose lines (lines connecting points of equivalent dose) as presented in the Table. to a total dose of 60.0 Gy in 2.0 Gy fractions of average hair density. We compared the control administered over 6 weeks with a 4–field beam biopsy with the alopecia biopsy to demonstrate arrangement (left anterior oblique, left posterior the depths of typical and destroyed structures oblique, left lateral, vertex) using 6 MV photons. and to show the difference in dermal thickness. The distribution of RT doses at depths of particular In the alopecia biopsy site, there were essen- isodose lines (lines connecting points of equivalent tially no follicles from 0.1 cm to 0.4 cm, which dose) is presented in Figure 1 and the Table. received between 19.35 and 32.2 Gy of radiation After RT, she began chemotherapy with temo- (Figure 1; Table). At a depth superficial to zolomide (October 2001–September 2002). She 0.2 cm, which received up to 19.35 Gy of first noticed hair loss during her second week radiation (Figure 1; Table), adnexal structures of radiation, with maximal hair loss at 5 weeks were damaged. The dermis was thin when com- of RT. At its worst, the area of alopecia cov- pared with the control, measuring 0.2 cm versus ered the entire superior aspect of her scalp. The 0.4 cm, respectively. The biopsy specimen from peripheral areas began to regrow during her che- the left parietal scalp (Figure 3) showed an intact motherapy, approximately 1 to 2 months after epidermis. Eccrine ducts and orifices were pres- discontinuing RT. ent. The outer root sheath was present above the On physical examination, the patient had sebaceous glands. The dermis showed a decreased average hair density, except for a residual area of number of follicular units. The follicles were alopecia on the left temporoparietal scalp. Within either truncated just below the sebaceous glands this area, there was a linear surgical scar and an (Figure 4) or were miniaturized anagen follicles. area of decreased hair density (Figure 2). There Truncated follicles showed buds of germinal fol- was a progressive decreasing density gradient licular epithelium below the level of sebaceous peripherally to centrally, with only miniaturized glands but no deeper than just below the seba- hairs remaining centrally. The follicular orifices ceous glands. Miniaturized anagen follicles were were present and the skin was not bound down, seen originating in the lower reticular dermis atrophic, or obviously fibrotic, except along the and showed intact internal and external root surgical scar. sheaths. Sebaceous glands and arrector pili mus- Punch biopsy specimens (4 mm) were obtained cles were present; however, the sebaceous glands from the area of alopecia on the left parietal scalp were small, with decreased numbers of lobules (Figure 3) and compared with a control biopsy when compared with the control. Eccrine glands taken from uninvolved occipital scalp at an area were present in the lower reticular dermis but 148 CUTIS® Cicatricial Alopecia Figure 4. An intact epidermis and hypoplastic seba- ceous glands in a punch biopsy specimen from the area of alopecia on the left parietal scalp. A truncated follicle also was present (H&E, original magnification 310). Figure 2. Area of alopecia on the left temporo- parietal scalp. Figure 3. Punch biopsy specimen (4 mm) obtained from the area of alopecia on the left parietal scalp Figure 5. Streamers of scarred follicles were present in (H&E, original magnification 32). the subcutaneous fat (H&E, original magnification 320). VOLUME 81, FEBRUARY 2008 149 Cicatricial Alopecia were decreased in number and size, with fewer normal due to the decreased diameter of the bul- acini per gland, and focally showed hyalinization bar remnant that it encased. At this stage, upon of the basement membrane. Subcutaneous fat pulling, many hair roots were found to be broken was present and was unremarkable. Streamers of off at a level immediately below the keratogenous scarred follicles were present in the subcutaneous zone. At 2 to 3 weeks following exposure, hairs fat (Figure 5). with tapered shafts and small keratinized bulbs were found. In many hairs, the keratogenous zone Comment was absent and evidence of complete cessation of In 1896, one year after Roentgen discovered growth was apparent. Other hairs that retained x-rays, Daniel4 reported that x-radiation caused the keratogenous zone continued to produce hair loss of hair in the human scalp. During the first shafts, but the shafts were markedly thinned. 2 decades of the 20th century, x-ray epilation of the The proportion of hairs showing these dysplastic face for hirsutism was frequently utilized.5 In 1906, changes were greater in sites receiving the higher Williams6 observed that the roots of hair epilated doses of radiation.13 by x-ray were pointed in configuration and hairs In 1940, McCarthy10 described 3 grades of skin that did not fall out spontaneously after exposure reactions to x-rays. A first-grade reaction appears to radiation and continued to grow had markedly within 16 to 21 days of x-radiation and consists constricted shafts. of scarcely perceptible erythema and slight scali- X-ray epilation for the treatment of tinea capi- ness of the skin with loss of hair. Healing takes tis was standardized by Kienböck7 in 1907 and place with regrowth of the hair in 2 to 4 months. Adamson8 in 1909 and used a suberythema dose. A second-grade reaction occurs within a week of The radiation dose from this technique ranged x-radiation with very marked edema and ery- from 500 rad (5 Gy) to 800 rad (8 Gy).9 Epilation thema, often with vesicle formation.