|Year : 2014 | Volume
| Issue : 1 | Page : 203-206
Postradiation hypertrichosis: A paradox
Jai Prakash Agarwal1, Maheshkumar N Upasani1, Yogesh Ghadi2, Anusheel Munshi1
1 Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
2 Department of Medical Physics, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
|Date of Web Publication||23-Apr-2014|
Jai Prakash Agarwal
Department of Radiation Oncology, Tata Memorial Hospital, Dr. Ernest Borges Road, Parel, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
Alopecia due to radiation has remained a widely accepted aspect of radiotherapy. We present an unexpected clinical scenario, where a patient with left lung stage IIIB nonsmall cell adenocarcinoma, treated with radiochemotherapy achieved a complete response and developed an obscure late effect in terms of paradoxical hypertrichosis in the radiation portals. The paper presents plausible hypothesis for this unusual phenomenon.
Keywords: Alopecia, late effects, postradiation hypertrichosis, radiotherapy
|How to cite this article:|
Agarwal JP, Upasani MN, Ghadi Y, Munshi A. Postradiation hypertrichosis: A paradox. J Can Res Ther 2014;10:203-6
| > Introduction|| |
Alopecia with radiation has remained a widely accepted aspect of radiotherapy even in this era where modern, precise, and accurate treatment delivery systems are available to spare the normal tissue. Indeed, the effect of radiation on hairs represents one of the first observations of the biological effects of the ionizing radiation. Within a few months of the discovery of X-rays by Röntgen, "the depilatory action of X-rays" was reported by Professor John Daniels in 1896.  Being a new discovery, it was purported and used for cosmetic epilation of superfluous hair. Thankfully, the harmful effects of this were realized over the period of time and this practice was stopped. The effect or rather the adverse effect of alopecia due to radiation has always been taken for granted or plainly ignored in pursuit of treatment of the cancer. Here, we present a related clinical circumstance which is rare and at first goes against the conventional reasoning.
| > Clinical Scenario|| |
A case of 54-year-old male presented with left-sided chest pain, associated with cough. On examination and investigation, he was diagnosed with carcinoma of left lung stage IIIB nonsmall cell adenocarcinoma He was treated with megavoltage (combination of 6 and 15 MV energy) external beam radiation with three-dimensional conformal technique using three coplanar beams to a dose of 60Gy in 30 fractions over 44 days to the chest and also received concomitant chemotherapy paclitaxel and carboplatin every week for 6 weeks. He tolerated the treatment well with acceptable acute toxicity of skin hyperpigmentation (RTOG grade II) and oesophagitis (RTOG grade I).
On the first follow-up, patient was controlled clinically with mild hyperpigmentation of skin and sparse aberrant hair growth over skin of the site of radiation portals. This area corresponded to the entry and exit of beams [Figure 1]. At subsequent follow-up also this hair growth and hyperpigmentation over the trunk persisted and the hair density increased. This was unexpected, especially because megavoltage energy is supposed to have skin sparing effect and the hair growth was restricted only to the skin surface of radiation portals. The effect was prominently noticeable because of the fact that he had very sparse hair over the adjacent body areas, including over back or chest. To rule out recurrence of disease and possible paraneoplastic syndrome-related hair growth, we did a 18 F-fluoro-deoxyglucose positron emission tomography-computed tomography at 3 months and again at 6 months posttreatment. Both the scans suggested complete metabolic and morphological response. We documented persistent hair growth till last follow-up which was at 2 years after radiation.
This intriguing phenomenon of increased hair growth in the radiation portals made us check the dose received by skin. The skin dose as per the planning system (Eclipse version 8.6, Varian Medical Systems) was 9 Gy [Figure 2]. Since planning systems are not efficient in calculating skin dose, we did a retrospective phantom-based surface dosimetry study to quantify approximate skin doses received by patient. A mix D torso phantom was used for this study. Field portals and energy were replicated as per the treatment plan. Dose was prescribed at the same isocenter. The surface dose was measured using five thermoluminiscent dosimeters (TLDs) placed at different points. Lateral and longitudinal placement of TLDs was decided such that it exposed completely in the junction area of two fields on phantom surface. TLD arrangement for the phantom was as shown in [Figure 3]. A dose of 10 Gy in a single fraction was delivered. The measured dose for TLD ranged from 2.19 Gy to 3.77 Gy which amounted to a range of 20%-34% of the total dose (average of 30.6%) delivered.
|Figure 1: Photograph of patient posttreatment, showing hyperpigmentation in radiation portals and hypertrichosis confined to the region of radiation portal. Panel (a) Anteriorly shows hair growth and hyperpigmentation in radiation portals over chest and shoulder. Panel (b) Posteriorly shows hair growth and hyperpigmentation in radiation portals over left back|
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|Figure 2: Color wash on the planning system (Eclipse version 8.6) showing the minimum dose 9 Gy reaching the skin and subcutaneous tissue|
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|Figure 3: Arrangement of the thermoluminiscent dosimeter for the phantom experiment. It shows the beams eye view and the reference points where the thermoluminiscent dosimeters were placed on the phantom and their distances from the isocenter|
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| > Discussion and Plausible Hypotheses|| |
Alopecia, loss of sebaceous and sweat glands in radiated sites is a dose-dependent phenomenon that can be temporary or permanent as happens to other normal tissue. Radiation-induced alopecia can be temporary effect due to anagen arrest and patients can usually recover from this after variable time interval. But sufficiently high dose of radiation used for treating malignancies can result in permanent destruction of the hair follicles leading to permanent alopecia. The mention of possibility of hair loss causes anxiety and psychological distress in patients who require radiation treatment. Similarly for patients on treatment, hair loss may dent their self-confidence due to poor body image.
Borak and Leddy  studied the doses of orthovoltage radiation that were lethal for epithelium in the epidermis and appendages concluding that the dose equivalent of 16 Gy is lethal for the hair follicles. Severs et al.,  also reconfirmed these findings and reported lethal dose for the hair follicles to be 16 Gy. Of course, the effect depends on the dose per fraction, volume of skin irradiated, total dose, and overall treatment time. Geary  also reported that hairs in the anagen phase were much more susceptible to radiation and had poor regrowth than those in the telogen phase. We performed an extensive english literature search for possible reports or cause of hair regrowth in radiation portals. However, we were unable to find any reports supporting or explaining this phenomenon. This leaves us to theorize and extrapolate the sparse knowledge to arrive at a meaningful plausible explanation for this unusual and unexpected phenomenon.
Hypertrichosis results when telogen or resting follicles are stimulated into anagen (phase of active growth) or when nonpigmented vellus hair follicles are converted into longer, darker terminal hair follicles. Hypertrichosis can be congenital (hypertrichosis lanuginosa) or acquired (iatrogenic) from medications such as cyclosporine, steroids, penicillin, and streptomycin. Sunlight has also been identified as having the tendency to induce hypertrichosis and agents such as psoralens or porphyrins can potentiate it possibly due to prostaglandin generation by the ultraviolet radiation.
There are several reports that explain rare event of hypertrichosis when lasers are used for hair ablation. ,,] The phenomenon of an increase in hair density, color, or coarseness, or a combination of these at treated sites in the absence of any other known cause of hypertrichosis has been called by different names including "paradoxical hypertrichosis", "terminalization", "induction," and "terminal hair growth".  Paradoxical hypertrichosis was first described by Moreno-Arias et al., , as growth of hair in untreated areas in close proximity to areas treated with lasers. In many studies, the explanation for increased hair growth with laser ablation is that suboptimal thermal energy is delivered to nearby follicles which results in induction of the hair follicle cycle. , We can extrapolate this theory to the effect of radiation; that is the dose received by at least few hair follicles was sublethal to an extent that they managed to escape the lethal damage and instead it led to further stimulation of these follicles thereby causing terminalization of hair or hypertrichosis in the radiation portals.
Another explanation may be with the presence of adipose-derived stem cells (ASCs) in the subcutaneous fat. ASC are regarded as an abundant and reliable source of stem cells for tissue regeneration. ASC exerts multiple beneficial effects by secreting growth factors, thereby promoting new hair growth. Intracellular reactive oxygen species (ROS) constitute an important stimulus for ASC that leads to hair growth promotion. , Radiation also acts by generation of free radicals and ROS, which might possibly explain the stimulation of the ASCs to lead to hypertrichosis in radiation portals. ROS is harmful in high quantities as it causes cellular apoptosis. Low or moderate ROS generation increase the proliferation, migration, and regenerative potential of ASCs. So it is possible that the low to moderate amount ROS were produced by radiation which stimulated the ASCs. These ASCs then further caused increase in the hair follicular differentiation.
Third alternative possibility is that the stem cells in the existing hair follicle or the basal layer of the dermis received doses of radiation, due to which they were directly stimulated into differentiation which led to increased hair growth limited to radiation portal. Hence, knowing the dose delivered to the surface was important. The dose calculated on the planning system was lesser than the dose by the TLD study, possibly due to the known fact of inherent inability of the calculation algorithms to specifically report accurate surface doses. The dose as per the TLD is just above the reported alopecia doses. It is possible that this dose was sublethal for the stem cells that further differentiated to cause hypertrichosis.
Concurrent chemotherapy agents also cause alopecia. Cytotoxic chemotherapeutic drugs act on the highly mitotic and proliferative matrix cells of the hair bulb during the anagen phase. This ceases the hair production and leads to anagen effluvium.  However, the effect is dose-dependent and also on the stage of hair growth. If the majority of hairs are not in anagen phase, then chemotherapeutic agents may possibly not produce alopecia. The alopecia, thus, produced is generally reversible after cessation of chemotherapy. In our patient, the effect of chemotherapeutic agent does not seem to have any unusual or unpredictable effects on hair follicles. Many methods have been tried to prevent alopecia due to chemotherapeutic agents and also due to radiation without much success. This case presents an opportunity to have a fresh look on possibility of alopecia prevention with radiotherapy as well as chemotherapy.
| > Conclusion|| |
Though there are several theories to explain this unusual phenomenon, either any one or all of these hypotheses might be plausible. This case also highlights the unique capability of the body normal tissue to respond to the lethally damaging radiation in an unusual way. The possible postulates proposed with regards to this unusual situation should trigger research in the arena of skin and hair sparing radiotherapy, especially in cosmetically important areas such as the scalp and face. Indeed there has been at least some work in trial settings to test drugs to prevent radiation-induced alopecia. However, it would be best if we could get away with just some tinkering and tweaking of the delivered dose to avoid radiation-induced alopecia.
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[Figure 1], [Figure 2], [Figure 3]