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British Journal of Radiology 75 (2002),478-481 © 2002 The British Institute of Radiology

Case report

The comedo skin reaction to radiotherapy

W M C Martin, FRCR, FRCP, PhD 1 and A F Bardsley, MB ChB, FRCS (Plastic Surg) 2

1 Oncology Department, Norfolk and Norwich Hospital, Brunswick Road, Norwich NR1 3SR and 2 Plastic Surgery Department, West Norwich Hospital, Bowthorpe Road, Norwich NR2 3TU, UK


   Abstract
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 Abstract
Case report
 Discussion
 References
 
A 50-year-old man had a maxillectomy and post-operative radiotherapy for squamous carcinoma of the maxilla. The acute skin reaction merged at 2 months into a chronic comedo-type acneiform skin reaction in the irradiated area. Previous literature on this reaction to radiation is reviewed. The reaction is rare and occurs mostly in the head and neck area, more commonly in patients who have received acneigenic drugs, and with a latent period of between 2 weeks and 6 months from completion of radiotherapy. The pathogenesis of acne is discussed and a mechanism of post-irradiation acne is suggested.


   Case report
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 Abstract
 Case report
Discussion
 References
 
A 50-year-old man presented with an abscess in the left upper eyelid. An opaque frontal sinus was noted on plain radiography, CT showed opacification and a left inferior medial antrostomy revealed solid tumour in the antrum from which biopsy showed squamous carcinoma. At left maxillectomy, tumour was found extending towards the orbital floor but the orbital periosteum was not involved. The left maxilla, left ethmoid sinus and floor of the orbit were resected with reconstruction of the orbital floor with free bone graft and reconstruction of the maxillary cavity, nasal wall and palatal mucosa with a myocutaneous rectus abdominus free flap. Histology showed tumour close (0.1 mm) to the upper medial resection margin. Two left submandibular nodes were clear of tumour. Post-operative radiotherapy was given to the left maxilla using a three-field technique (supero-oblique, anterior and infero-oblique) to a tumour dose of 50 Gy/25 fractions (F) over 41 days with full bolus to the cheek and a 6 Gy/3F boost was given to the region of close margin using 7 Me V electrons.

Acute radiation reactions occurred in the skin, left eye, left nasal cavity and oral cavity. These all settled following treatment with, respectively, E45 (Crookes Healthcare Ltd, Nottingham, UK) cream changing to hydrocortisone cream in the third week, hypromellose drops and later prednisolone eye drops, betamethasone-neomycin nasal drops and mouthwashes for oral mucositis. 2 months after completion of radiotherapy a comedo–type acneiform skin reaction developed over the left cheek and nose, within the area of radiation pigmentation (Figure 1Go). This persisted despite use of various topical acne treatments. There was also an ectropion. The patient later developed a sinus in the left lower eyelid connected to the metal fixation plate beneath, and 12 months after initial surgery the left maxillary wound was re-explored with removal of metal work and release of the cicatricial ectropion with a small scalp flap.



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  		Figure 1. The comedo reaction within the area of radiation pigmentation.

 
18 months following maxillectomy, the comedones were treated with a comedo extractor. 5 years post-maxillectomy he remains clinically free both of tumour and comedos (Figure 2Go).



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  		Figure 2. The patient, 2 years after radiation therapy.

 

   Discussion
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 Abstract
 Case report
 Discussion
References
 
The first observation of an acneiform reaction to radiation was by Bluefarb in 1947 who reported a ring of comedos at the margin of a superficial radiation field [1]. These occurred 3 months after treatment of a squamous carcinoma of the face. Ronchese [2] confirmed this in three cases of basal carcinoma treated with superficial irradiation. Swift [3] reported comedones and pustules in the whole irradiated area of a female patient who had received orthovoltage treatment to the thoracic spine for metastatic breast carcinoma 6 months earlier. The patient was taking testosterone, an acneigenic drug, and had suffered from acne at the age of 14 years, yet the rash was limited solely to the irradiated area. Stein et al [4] were the first to describe a comedo reaction following cobalt irradiation in a patient who had also received steroids and isoniazid. Other reports of this phenomenon following megavoltage radiation have appeared. Table 1Go summarizes the literature on this subject and includes our case report [5–16].


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  		Table 1. Literature summary on radiogenic acne

 
Using the available data in Table 1Go, the male: female ratio can be seen to be 15:11. The age range is 26–75 years, with all decades represented. All patients were above the normal age for development of acne. All body sites were affected, from the scalp to the pelvis, but 16 of 27 cases occurred on the scalp, face or neck. The radiation doses were radical in all cases except that of the of aforementioned patient who received orthovoltage treatment and testosterone. The latent periods were between 2 weeks and 6 months. Steroids, isoniazid, anti-convulsants and LHRH analogues are known to be associated with acne. Of the 27 cases in Table 1Go, data on drug therapy are not available for 11 cases. Of the remaining 16 cases, 8 had recently received treatment with an acneigenic drug, 3 had undergone treatments with drugs not known to be associated with acne (tamoxifen, BCNU) and 5 had received no drug therapy. Where a previous history was available (in 15 of 27 cases), 6 had suffered acne as children or teenagers, a proportion not markedly different from the general population.

Therefore, while the comedo reaction can occur at any site, there appears to be a predilection for the scalp, face or neck and the reaction is more common in patients who have recently received acneigenic drugs. A history of acne earlier in life does not seem to be a significant risk factor.

It is now accepted that comedo production is caused by over-proliferation of sebaceous ducts, retention of hyper-proliferating ductal keratinocytes in these ducts and formation of a keratin plug [17]. Factors implicated in its pathogenesis include sebaceous lipid composition, especially linoleate, androgens, local cytokine production and bacteria. Linoleate levels are reduced in sebum from acne sufferers but return to normal with resolution of the acne following treatment with isotretinoin [18] or anti-androgens [19]. In animal experiments a low linoleate level produces hypercornification similar to the increased scale seen in comedones [20]. There is evidence that androgens have a role in comedogenesis since cells of the pilosebaceous duct have androgen receptors [21] and drugs containing cyproterone acetate reduce comedones and also increase sebum linoleate concentration [19]. Interleukin 1-alpha is present in many comedones at significant levels [22] and can also induce comedogenesis in vitro [23]. The organisms Propionibacterium acnes, Staphylococcus epidermidis and Malassezia furfur [24] are commonly isolated from the skin surface and sebaceous ducts of patients with acne and may cause the comedo to become inflamed, but are not now thought to be involved in the initiation of comedones [20].

Irradiation is known to reduce the amount and composition of sebum produced. It therefore seems likely that the pathogenesis of radiation–induced comedos relates to changes in lipid composition in sebum leading to duct hyperproliferation. Following megavoltage radiation, a differential effect exists in the dose to various points in the pilosebaceous apparatus and this may also be a factor. Skin tumours will often have already damaged the pilosebaceous apparatus, and this may explain why the early radiotherapists using superficial radiation saw the ring of comedones only at the margin of the irradiation field.

Our patient's comedones were removed with a comedo extractor. Other treatments for acne include antiseptic cleansing agents, keratolytics such as benzoyl peroxide, topical or oral antibiotics and topical or oral retinoids. Results are generally good. Radiation itself has been used in the past and this is presumably effective because radiation suppression of pilosebaceous gland activity can lead to skin cleansing [6].


   Acknowledgments
 
We wish to thank the nurses of West Norwich Hospital for excellent nursing care, the therapy radiographers of Norfolk and Norwich Hospital for efficiently planning and treating this patient, Clare Wilson for typing the manuscript and Dr Nick Levell and Dr Andrew Bulman for their most helpful comments. We also wish to thank the patient for giving his permission to use facial photographs.

Received for publication December 4, 2001. Accepted for publication January 7, 2002.


   References
Top
 Abstract
 Case report
 Discussion
 References
 

  1. Bluefarb SM. Comedos following roentgen ray therapy. Arch Dermatol Syph 1947;56:537–9.
  2. Ronchese F. Cicatricial comedos and milia. Arch Dermatol Syph 1950;61:498–500.
  3. Swift S. Localized acne following deep x-ray therapy. Arch Dermatol 1956;74:97–8.[Abstract/Free Full Text]
  4. Stein KM, Leyden JJ, Goldschmidt H. Localized acneiform eruption following cobalt irradiation. Br J Dermatol 1972;87:274–9.[Medline]
  5. Trunnell TN, Baer RL, Michaelides P. Acneiform changes in areas of cobalt irradiation. Arch Dermatol 1972;106:73–5.[Abstract/Free Full Text]
  6. Engels EP, Leavell U, Maruyama Y. Radiogenic acne and comedones. Radiol Clin Biol 1974;43:48–55.[Medline]
  7. Larsen FS, Heydenreich G, Christiansen JV. Comedo formation following cobalt irradiation. Dermatologica 1979;158:287–92.[Medline]
  8. Walter JF. Cobalt radiation-induced comedones. Arch Dermatol 1980;116:1073–4.[Abstract/Free Full Text]
  9. Finn OA. Localised acneiform eruption following X-ray therapy. Br J Clin Pract 1981;35:57–8.[Medline]
  10. Myskowski PL, Safai B. Localized comedo formation after cobalt irradiation. Int J Dermatol 1981;20:550–1.[Medline]
  11. Aversa AJ, Nagy R. Localized comedones following radiation therapy. Cutis 1983;31:296–303.[Medline]
  12. Adriaans B, du Vivier A. Acne in an irradiated area (letter). Arch Dermatol 1989;125:1005.[Abstract/Free Full Text]
  13. Klemke CD, Nestoris S, Wolfer L-U, Krengel S, Zouboulis CC, Tebbe B, et al. Radiogene akne. Hautarzt 2000;51:187–91. (In German.)[Medline]
  14. Friedman SJ, Su WPD. Favre-Racouchot syndrome associated with radiation therapy. Cutis 1983;31:306–10.[Medline]
  15. Karrer S, Schäfer CB, Allgäuer M, Landthaler M. Acne comedonica nach strahlentherapie. Dtsch Med Wochenschr 1998;123:527–30. (In German.)[Medline]
  16. Hepburn NC, Crellin RP, Beveridge GW, Rodger A, Tidman MJ. Localized acne as a complication of megavoltage radiotherapy. J Dermatol Treat 1992;3:137–8.
  17. Plewig G, Fulton JE, Kligman AM. Cellular dynamics of comedo formation in acne vulgaris. Arch Dermatol Forsch 1971;242:12–29.[Medline]
  18. Downing DT, Stewart ME, Wertz PW, Strauss JS. Essential fatty acids and acne. J Am Acad Dermatol 1986;14:221–5.[Medline]
  19. Stewart ME, Greenwood R, Cunliffe WJ, Strauss JS, Downing DT. Effect of cyproterone acetate-ethinyl estradiol treatment on the proportion of linoleic and sebaceic acids in various skin surface lipid classes. Arch Dermatol Res 1986;278:481–5.[Medline]
  20. Cunliffe WJ, Simpson NB. Disorders of the sebaceous glands. In: Champion RH, Burton JL, Burns DA, Breathnach SM, editors. Text book of Dermatology Vol 3, (6th edn). Blackwell Science, 1998.
  21. Choudhry R, Hodgins MB, Van der Kwast TH, Brinkmann AO, Boersma WJ. Localisation of androgen receptors in human skin by immunocytochemistry. J Endocrinol 1992;133:467–74.[Abstract/Free Full Text]
  22. Ingham E, Eady A, Goodwin CE, Cove JH, Cunliffe WJ. Pro-inflammatory levels of interleukin-1 alpha–like bioactivity are present in the majority of open comedones in acne vulgaris. J Invest Dermatol 1992;98:895–901.[Medline]
  23. Guy R, Green MR, Kealey T. Modelling acne in vitro. J Invest Dermatol 1996;106:176–82.[Medline]
  24. Marples RR. The microflora of the face and acne lesions. J Invest Dermatol 1974;62:326–31.[Medline]
  25. Holland KT, Cunliffe WJ, Roberts CD. The role of bacteria in acne vulgaris—a new approach. Clin Exp Dermatol 1978;3:253–7.[Medline]




This Article
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Right arrow Articles by Bardsley, A F

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