A 48-year-old woman presented with traumatic injury secondary to removal of pubic hair using hot wax. Her medical history included long-standing type 1 diabetes mellitus, complicated by retinopathy, nephropathy and neuropathy. Because of diabetic complications, she had required a renal transplant five years before presentation and a pancreatic transplant two years later. Her anti-rejection medications included tacrolimus, mycophenolate mofetil and prednisone. Her past dermatologic history included melasma on the face.
Three years after her pancreatic transplant, the patient underwent “Brazilian” waxing. When the wax was pulled off the skin, the entire area was denuded and bleeding. The patient was assessed by a physician, and the traumatized area was allowed to heal by secondary intention. As the area healed, the patient noticed a violaceous discoloration in her pubic area and again sought medical attention. On examination, a purplish-red plaque over the mons pubis extending to the inguinal folds was observed. At the border of this plaque, brownish-red planar verrucous papules were noted, with sparing of the posterior aspects of the vulva, buttocks and perineal area (Figure 1). A biopsy was taken and sent for histopathology.
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Figure 1:
Clinical photograph of the groin of a 48-year-old woman showing purplish-red flat-topped verrucous papules coalescing into a confluent plaque over the mons pubis and labia. These flat wart-like lesions developed after pubic hair waxing.
Histopathology showed keratinocytes with changes consistent with the effects of human papillomavirus (HPV), and a diagnosis of epidermodysplasia verruciformis was made. She reported no personal or family history of this condition. We initiated a side-to-side comparison of treatment with liquid nitrogen cryotherapy on the right upper medial thigh and inguinal crease, and tretinoin 0.1% cream daily on the left side. On follow-up, the side treated with liquid nitrogen showed much more postinflammatory hyperpigmentation and less resolution of lesions, and the side treated with tretinoin showed more satisfactory flattening of the papules and minimal postinflammatory hyperpigmentation. There was some erythema and discomfort with the tretinoin treatment, but these adverse effects diminished with time.
Discussion
The issues raised in this case represent the intersection of several trends that are becoming increasingly important to physicians. First, there is a rise in the number of patients who are immunosuppressed.1 Not only is the number of solid organ transplant recipients growing, but so too is the number of patients taking immunosuppressive medication for a variety of inflammatory and autoimmune disorders. The second trend involves the increasing popularity of body modification, including partial or complete removal of body hair. One recent survey-based study found that more than 70% of teenage girls shaved or waxed their pubic hair on a regular basis.2 This predilection for hairlessness is also increasing among men. The methods used to remove body hair also include shaving, clipping, epilation, depilatory creams, laser hair removal, electrolysis, sugaring and threading. Many of these methods cause trauma that can provide an entry point for infection.
Because of a lack of controlled trials on the risks and adverse effects of techniques for body hair removal, case reports provide most of our insight into the risks of body hair removal. One report discussed a patient with diabetes mellitus in whom life-threatening Streptococcus pyogenes and herpes simplex virus infections developed after Brazilian waxing.3 In another case report, an outbreak of methicillin-resistant Staphylococcus aureus was linked to cosmetic body shaving.4 Two cases of HPV infection linked to threading have been reported.5 These patients had facial hair removed by threading, and subsequently verrucae developed at the sites of hair removal. Furthermore, HPV has been shown to reside on pubic and perianal hairs.6 It follows that traumatic hair removal in these areas might result in an infection and subsequent clinical manifestation of HPV. In the case of our patient, HPV-associated epidermodysplasia verruciformis developed, secondary to pubic hair removal.
Epidermodysplasia verruciformis
There are two described subtypes of epidermodysplasia verruciformis, the classic type and the acquired type. Classic epidermodysplasia verruciformis is an autosomal recessive genodermatosis that increases susceptibility to particular HPV subtypes.7 The HPV subtypes that are commonly associated with epidermodysplasia verruciformis include HPV-5, -8, -9, -12, -14, -15, -17, -19, -25, -36, -38, -47 and -50.8 These HPV subtypes are also found on the skin of people without epidermodysplasia verruciformis; however, they are rarely pathogenic in immunocompetent individuals.9 Although the actual pathogenesis for the development of epidermodysplasia verruciformis has not been completely elucidated, it is widely hypothesized to be associated with defects in cell-mediated immunity.
Classic epidermodysplasia verruciformis begins in early childhood with flat wart-like papules and plaques on the extremities, neck, face and trunk. There is a high association with the development of squamous cell carcinoma, particularly in sun-exposed areas.9 Cutaneous malignancy will develop in about half of these patients by the fourth or fifth decade.9
Recently, an acquired form of epidermodysplasia verruciformis has been described in immunocompromised patients.7 Most of these patients are infected with HIV, but transplant patients taking antirejection drugs and patients with hematologic malignancy taking anti-neoplastic medications are also susceptible.7 The risk of malignant transformation secondary to acquired epidermodysplasia verruciformis is unknown, but clinical surveillance with appropriate follow-up is warranted given the risks associated with inherited forms of epidermodysplasia verruciformis.
As with many other HPV infections of the skin, epidermodysplasia verruciformis is associated with epithelial hyperplasia. Topical or systemic retinoids, which have an antiproliferative effect, can be used to control the growth of the epidermis. In addition, retinoids may provide the added benefit of slowing or preventing the progression to dysplasia and malignancy.10 In a few cases, systemic retinoids were combined with interferon, which provided an even better clinical response.8 In patients with classic epidermodysplasia verruciformis, imiquimod has been used topically with clinical improvement.8 Imiquimod is an immune response modulator that activates the immune system through toll-like receptor 7 (TLR-7) and is used commonly for treatment of verrucae and condylomata. Imiquimod is also used in the treatment of Bowen disease or squamous cell carcinoma in situ and as such may provide further benefit in treating dysplastic lesions or early malignancies. Topical cidofovir and topical podophyllotoxin have also been used, but the clinical results are not as reliable or substantial as those achieved with imiquimod or retinoids.7,8 Surgical approaches can also be used, including cryotherapy, electrodessication and curettage, as well as surgical excision.
Acquired epidermodysplasia verruciformis is more difficult to treat than the classic form.7 Topical imiquimod, topical 5-fluorouracil and isotretinoin have been tried in this patient group without success.7 Given the lack of evidence available regarding the ideal first-line treatment for acquired epidermodysplasia verruciformis, we engaged in a side-to-side comparison of topical versus destructive therapy to assess the best course of action for our patient. Changing the immune status by putting patients with HIV on effective antiretroviral therapy has had mixed results.8 Consideration can be given to altering the dose or type of antirejection medications in the transplant population, but the risks of rejection must be weighed against the unproven clinical effects on epidermodysplasia verruciformis.
Conclusion
We have presented a case of acquired epidermodysplasia verruciformis in a patient with immunosuppression whose infection was precipitated by pubic hair removal using hot wax. The growing demographic of patients who are immunosuppressed and the increasing prevalence of pubic hair removal suggest that cases such as this one may be seen more often in physicians’ offices. Hair removal techniques that minimize trauma to the epidermis, such as trimming or use of depilatory creams, should be discussed with patients who are immunosuppressed.
Key points
Because human papillomavirus (HPV) is commonly found on pubic and perianal hairs, techniques of body hair removal resulting in trauma may increase the risk of HPV-associated lesions.
Acquired epidermodysplasia verruciformis is a rare skin disorder commonly associated with HPV and immunosuppression.
Treatment with topical or systemic retinoids, topical imiquimod or destructive therapies may be considered for acquired epidermodysplasia verruciformis, although clinical effectiveness is highly variable.
Patients with immunosuppression should be counselled about the increased risk of infection from body hair removal and about use of hair removal techniques that minimize trauma.
Footnotes
Competing interests: Sheila Au has received funds from La Roche-Posay, Ono Pharmaceutical Co., Valeant Pharmaceuticals International Inc., Amgen, AbbVie, Galderma, Valeo Pharma and Janssen. No competing interests were declared by Mark Kirchhof.
This article has been peer reviewed.
The authors have obtained patient consent.
Contributors: Both authors drafted and revised the article, and approved the final version submitted for publication.
References
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Delirium is often missed
Although delirium is common (prevalence 18%–50% in hospital, up to 88% in palliative care),1,2 the diagnosis, particularly hypoactive delirium, is often missed owing to symptom fluctuation and transient lucidity, as well as clinical features that overlap those of dementia and depression.3 The diagnosis is clinical, but nursing observational and cognitive screening tools or brief tests of attention may improve detection. A collateral history of an acute change in mental status should prompt use of the Confusion Assessment Method.4,5
Delirium is usually multifactorial
Delirium arises from the interplay of predisposing (e.g., advanced age, dementia) and acute precipitating factors.1 Superimposed precipitants include infection, medications (e.g., psychoactive and anticholinergic drugs), drug withdrawal, metabolic abnormalities and other medical conditions. Delirium’s reversal hinges on the identification of treatable precipitants.
About one-third of all delirium episodes in older adults in hospital can be prevented
Multicomponent nonpharmacological interventions are effective for preventing and treating delirium in many patients.1 The Hospital Elder Life Program targets risk factors6 with a focus on orienting activities, hydration, sleep, mobility and avoidance of sensory deprivation. Unnecessary use of catheters should be avoided.7 Other strategies include comprehensive geriatric assessment perioperatively, use of designated delirium rooms and comprehensive medication review.
Benzodiazepines should be avoided as first-line agents in the pharmacologic management of delirium
Benzodiazepines can exacerbate delirium; first-line use is limited to the management of alcohol or sedative-hypnotic withdrawal (Box 1). Limited evidence suggests short-term use of antipsychotic agents (e.g., haloperidol, olanzapine) in the lowest clinically effective doses for the management of severe hyperactive (agitated) delirium.7 Anti-psychotic agents should be used cautiously in Parkinson disease or Lewy body dementia, because of the risk of extrapyramidal adverse effects.
Box 1:
Choosing Wisely Canada recommendation
Do not use benzodiazepines or other sedative–hypnotic agents as first-line treatment in older adults with insomnia, agitation or delirium.
Large-scale studies consistently show that the risk of motor vehicle collisions, falls and hip fractures leading to hospital admission and death can more than double in older adults taking benzodiazepines and other sedative–hypnotic agents. The number needed to treat with a sedative–hypnotic for improved sleep is 13, whereas the number needed to harm is only 6. Older patients, their caregivers and their health care providers should recognize these potential harms when considering treatment strategies for insomnia, agitation or delirium.
Source: Canadian Geriatrics Society, Choosing Wisely Canada (www.choosingwiselycanada.org/recommendations/canadian-geriatrics-society-2/)
Delirium has a poor prognosis
Delirium is associated with increased mortality and morbidity; cognitive and functional decline are common, as is placement in long-term care.1,8 Symptoms usually persist, and recovery rates are poor in older patients. Delirium may worsen pre-existing and increase the risk of new-onset dementia.1 Patients may feel threatened and anxious.3 Family members should be provided with education and support.
CMAJ is collaborating with Choosing Wisely Canada (www.choosingwiselycanada.org), with support from Health Canada, to publish a series of articles describing how to apply the Choosing Wisely Canada recommendations in clinical practice.
Acknowledgements
See Appendix 2, www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.141248/-/DC1.
Footnotes
See references, www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.141248/-/DC1
Competing interests: None declared.
This article has been peer reviewed.
A 52-year-old man presented with redness and irritation of the left eye. He had tried using artificial tear drops and gels without much benefit. On examination, the patient had redundant, wrinkled eyelid skin bilaterally with a greater amount on the affected side (Figure 1A). Ptosis of the left upper eyelid was evident, and the upper eyelashes were inverted. These lashes were in contact with the cornea, which showed chronic inflammatory changes. Diffuse, punctate epithelial defects were evident after fluorescein staining of the cornea. Slit-lamp examination showed papillary conjunctivitis. The left upper eyelid was easily distracted and everted (Figure 1B). The findings were characteristic of floppy eyelid syndrome.
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Figure 1:
(A) Redundant, wrinkled eyelid skin, particularly of the left eye, in a 52-year-old man with floppy eyelid syndrome. Ptosis of the upper eyelid is evident, and the upper eyelashes are inverted. (B) Superior distraction of the upper eyelid without eversion, showing extreme laxity, folds in the usually firm tarsal plate (*) and diffuse papillary conjunctivitis involving the bulbar and palpebral conjunctiva.
Floppy eyelid syndrome is observed most often in men who are obese (body mass index ≥ 30). There are no reliable prevalence data, and no other risk groups have been identified. The precise pathophysiology remains undefined, but histopathologic studies have shown depleted levels of elastin within the tarsal plate of the eyelid, in the skin of the eyelid and adjacent to the lash roots.1 There is an association with obstructive sleep apnea, which is believed to be an epiphenomenon.2 Although there is no proven causal link, it is important to screen for symptoms of sleep apnea in patients with floppy eyelid syndrome because the estimated prevalence is 21%–100%.2
Shielding the eye while sleeping can prevent eversion of the eyelid from contact with a pillow and eliminate direct abrasion. Patients with obstructive sleep apnea who use a continuous positive airway pressure device often benefit from the imposed supine sleep position, which prevents eyelid–pillow contact.
Obstructive sleep apnea was diagnosed previously in this patient, but he could not tolerate wearing a continuous positive airway pressure device while sleeping. A horizontal tightening procedure was performed on the upper and lower eyelids, which alleviated his symptoms.
Clinical images are chosen because they are particularly intriguing, classic or dramatic. Submissions of clear, appropriately labelled high-resolution images must be accompanied by a figure caption and the patient’s written consent for publication. A brief explanation (250 words maximum) of the educational significance of the images with minimal references is required.
Footnotes
Competing interests: None declared.
This article has been peer reviewed.
The authors have obtained patient consent.
References
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- Schlötzer-Schrehardt U,
- Stojkovic M,
- Hofmann-Rummelt C,
- et al
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- Fowler AM,
- Dutton JJ
We recognize the desire to produce a “Five things to know about …” article for a common clinical condition. After all, the popular press constantly barrages us with similar entertaining lists of facts we didn’t know about certain things. Squissato and Brown1 have selected some interesting articles on which to comment from many thousands of possible articles. The danger of this approach was that it was completely at the discretion of the authors to select what they considered important topics and to hopefully then give an unbiased assessment of that topic. The article does not cite any of the 12 available Cochrane reviews on the topic of carpal tunnel syndrome.
For the most part, the article does a good job of simplifying the current knowledge. However, we take issue with point five regarding treatment of carpal tunnel syndrome. The authors based their recommendation on a small randomized-controlled trial comparing wrist splints and an educational program and a control group who received nothing.2 Perhaps not surprisingly, the control group experienced a dropout rate of over 22% compared to 3% in the treatment group. This obviously places the internal (and therefore external) validity in question. The study ultimately went on to show an advantage to the splint group. But why include this study in the first place when there is a Cochrane systematic review published just the year before that looked at 19 studies of wrist splints with almost 1200 patients enrolled?3
We have concerns about the recommendation to consult an occupational therapist for splinting. Wrist splints are available and inexpensive, and basic advice on activities to avoid is within the purview of the primary care practitioner. We suggest referral to an occupational therapist or orthotist only when over-the-counter splits don’t fit well (such as carpal tunnel syndrome associated with rheumatoid arthritis) to avoid delay in initiating treatment and additional expense.
More worrisome is Squissato and Brown’s1 conclusion that, “if symptoms do not improve within eight weeks, referral to a surgical specialist should be considered.” There is no evidence that eight weeks of splinting is the limit. This recommendation could lead to unnecessary surgical consultations. There is no mention of electrodiagnostic studies in the diagnosis and monitoring of the condition and no mention of the one treatment that has the best evidence of efficacy in carpal tunnel syndrome, corticosteroid injection.4
Footnotes
Competing interests: Ashworth and Tardiff coauthored the Cochrane review on corticosteroid injection.
References
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- Squissato V,
- Brown G
- ↵
- Hall B,
- Lee HC,
- Fitzgerald H,
- et al
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- Page MJ,
- Massy-Westropp N,
- O’Connor D,
- et al
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- Marshall S,
- Tardif G,
- Ashworth N
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