Focus on Acne - Anthony Chu, FRCP. Professor of Dermatology

Acne is the commonest dermatosis to affect man but is generally poorly treated. It has a major genetic component (1) and must be regarded as a chronic inflammatory disease. It can scar the skin and the psyche causing lack of self-esteem, mood swings, depression and suicidal ideation (2).

Acne has changed significantly over the last 5 decades. In the 1970s, it was considered a teenage disease and would naturally resolve in about 5 years. A population-based study in USA (3) has confirmed our clinical impression that acne is now persisting in a high percentage of patients and it is impossible to predict when resolution will occur. In this study the incidence of acne at the age of 30-40 years was 35% in women and 20% in men and in those over 50 years, 15% in women and 7% in men. One possible reason for this is increased stress in modern society with stress stimulating adrenal gland function and increasing androgen production.

To treat acne properly you need to understand the pathophysiology of the disease, which has 4 important steps (4). 1. Sebum production is abnormally high due to an end organ response to normal levels of androgens and the sebum is deficient in linoleic acid. 30% women have higher androgen levels are part of the polycystic ovary syndrome. 2. Hyperkeratosis at follicular ostium restricts oil flow onto the skin. This is the first morphological change with the formation of the microcomedone. 3. Follicular occlusion leads to pooling of oil in the follicle which stimulates proliferation of the anaerobic commensal bacterium, Propionibacterium acnes, recently renamed Cutibacterium acnes. 4. Inflammation is induced by T helper cells reactive to C acnes antigens (5) with ultimate pus formation. Acne is a primary inflammatory disease of the skin and not an infection and C acnes does not fulfil Kock’s postulates.

Treatment

The treatment of acne has not fundamentally changed over the last 4 decades. In Primary Healthcare, topical or oral antibiotics are the mainstay with the use of topical retinoids. Antibiotics target the inflammatory lesions of acne but have no effect on the non-inflammatory microcomedones and comedones and must always be used with agents that will target these.

Non-inflammatory lesions

The major treatment are the topical retinoids. Retinoids normalise keratinocyte growth and thus prevent follicular hyperkeratinisation. The topical retinoids now available in UK are tretinoin, as a 0.025% cream or in combination with 1% clindamycin (Treclin gel) or 4% erythromycin (Aknemycin plus lotion), and adapalene as a 1% cream or gel or in combination with 2.5% benzoyl peroxide (Epiduo gel). Studies have shown that the absorption of topical retinoids is minimal. Topical retinoids can cause local photosensitivity so should be used at night and washed off in the morning. They may cause local skin dryness and irritation but this is often due to overuse. Microcomedones cannot be seen with the naked eye so all affected areas should be treated, not just where spots are present.

Salicylic acid is a desmolytic agent breaking down bonds between keratinocytes. 2% preparations are available OTC and can help reduce follicular hyperkeratosis. Azelaic acid as a 20% cream (Skinoren) has some comedolytic effects but its main effect in acne is on the inflammatory lesions

Inflammatory lesions

Antibiotics

Antibiotics work partly by killing C acne but have significant anti-inflammatory activity and studies in my laboratory have shown that antibiotics work in suppressing inflammatory acne lesions even when C acnes are resistant to them (6). The most common oral antibiotics used in acne are oxytetracycline and erythromycin, which are possibly the worst antibiotics to use due to their bioavailability. Oxytetracycline has a half-life of 6-8 hours and is inhibited by fat or iron in the stomach. Erythromycin has a half life of about 2 hours and is inhibited by carbohydrate in the stomach. These antibiotics need to be taken at least four times a day, on an empty stomach and without eating for a further hour – almost an impossibility for most patients

The newer tetracyclines such as lymecycline and doxycycline and macrolides such as clarithromycin have much improved bioavailability and should be used in preference. In patients not fully responding to a tetracycline or macrolide, trimethoprim, 300mg bd is a good second line drug (7)

Topical antibiotics achieve a high local concentration in the skin with minimal systemic absorption and thus side effects. Few are currently available – 1% clindamycin lotion or gel, 1% clindamycin with 3 or 5% benzoyl peroxide (Duac gel) and 4% erythromycin with zinc (Zineryt lotion). Drug resistance in C acnes quickly develops to topical antibiotics but this may not affect their efficacy. The addition of benzoyl peroxide prevents drug resistance from developing.

Non antibiotic treatments

Benzoyl peroxide is an organic peroxide used commercially to bleach flour. Pace was the first to use a preparation of benzoyl peroxide in acne in 1965 (8) and since then it has remained a highly effective and safe treatment. It works by releasing oxygen into the follicle where it kills anaerobic C acne. No resistance can develop which makes it an important treatment particularly in combination with antibiotics. Benzoyl peroxide preparation are available at 2.5 and 5%. They can cause skin irritation and more rarely act as a sensitiser. They also bleach fabric and clothing.

Aknicare lotion is a little known but very useful prescription or OTC treatment of acne. It contains triethyl citrate and ethylinoleate. These are metabolised in the follicle by C acnes to citric acid and linoleic acid. Citric acid reduces the pH inhibiting C acnes growth. It restricts bacterial enzyme reduction of sebum triglycerides maintaining integrity of sebum, reducing availability of glycerol to the bacteria, further restricting growth and supressing free fatty acid mediated inflammation. Linoleic acid and citric acid suppress 5α-reductase and thus the activation of testosterone. Clinical studies have shown that it is very effective in suppressing inflammatory lesions and significantly reduces sebum production (9). Linoleic acid increases the concentration of this in sebum and thus suppresses follicular hyperkeratinisation. It is particularly useful in women who are trying to conceive or who are pregnant where topical retinoids are contraindicated.

4% nicatinamide gel has anti-inflammatory activity and suppresses inflammatory lesion of acne but probably less effective than benzoyl peroxide. It has no effect on non-inflammatory lesions. 20% azelaic acid has anti-inflammatory activity.

Alternative treatments

Systemic drugs

Oral contraceptive pills containing cyproterone acetate (Dianette) or drospirenone (Yasmin) are effective in acne by suppressing androgen activity in women. They should be reserved for women who have severe acne not responding to conventional treatment. Both have significant side effects and Dianette can cause an initial flare of acne. In both drugs, acne may flare when the drug is stopped. Dianette is only recommended for short term us.

Spironolactone is an aldosterone blocking diuretic which also acts as an androgen receptor antagonist and at 100-200mg/day is very effective in women with hormonal acne (10). 10% women develop changes in their menstrual cycle. 

Dapsone is a sulphone drug with a major effect on the function of polymorphonuclear leukocytes. Worldwide it is a treatment for leprosy and in dermatology is the treatment of choice for dermatitis herpetiformis and various pustular dermatoses. In nodulocystic acne it can be very effective in reducing inflammatory lesions at 50mg/day. Patients should be screened for G6PD deficiency.

Oral isotretinoin is the most powerful drug we have to treat acne. It is licenced for the treatment of severe acne, acne not responding to conventional treatment or where there is a risk of scarring. It is, however, overused and often offered to patients with mild or moderate acne. It is a vitamin A derivative and is thus teratogenic and a pregnancy prevention program is used. Symptomatic side effects are common: dry skin, dry lips, photosensitivity, myalgias, arthropathy, night blindness and an effect on mental concentration. Most are self-limiting when the drug is stopped but up to 10% patients have long term xerosis. Patients must be warned of very rare but serious side effects which are totally unpredictable. These include acne fulminans, severe idiosyncratic depression and suicide (11), erectile dysfunction in men and loss of libido in women (12), severe persistent xerosis and cheilitis and fatigue syndrome. These severe side effects do not resolve on cessation of the drug.

Light and Lasers

Red light at 660nm aids healing by stimulating cytokine production. Blue light at 415nm activates coproporphyrin in C acne which kills the bacteria. Studies have shown that a system of red and blue fluorescent tubes were as effective as treatment with 5% benzoyl peroxide over a 12-week treatment period (13). Since that time a number of LED systems using red and blue light have become commercially available but none have been subjected to randomised clinical trials for efficacy

The Regenlite laser (formerly the NLite laser) is a pulsed dye laser with a unique waveform (see figure 1). This gives the laser a unique medical effect on the skin by inducing high levels of transforming growth factor β (TGF β) (14). TGF β is a potent anti-inflammatory cytokine which can induce T regulator cells, which in the case of acne, can turn off the immunological response responsible for the inflammation. Clinical trials have shown high efficacy in treating inflammatory acne requiring a single treatment every 3 months (15).

Figure 1. Pulse wave of Regenlite laser compared to traditional pulsed dye laser

Salicylic acid peels : Studies using a 30% salicylic acid peel with triethyl citrate and ethyl linoleate (Enerpeel SA) showed that after one application, the stratum corneum was reduced by 70%  and microcomedones were reduced (16). A sequence of this peel is medically licensed for the treatment of comedogenic and inflammatory acne and as an adjunct to conventional treatment, has an obvious place. 

Common Pitfalls

Why has treatment not worked? Most studies have identified user failure as the most common cause – patients not using treatment properly or not at all. The more complex the regime the less likely the patient will comply. Regular use of the topical retinoid, however, is essential in all acne patients.

If patients have very oily skin, oral antibiotics may be passed to the surface before they are able to work. In such cases, studies have shown that an increase in the antibiotic dosage can be effective (17)

Another common cause of treatment failure is the presence of macrocomedones. These are deep blockages in the follicle which may be invisible until the skin is stretched and the <1mm bump can be seen. These do not respond to topical retinoids and are the cause of recurrent deep inflammatory spots, particularly around the jawline in women. They are a contraindication to oral isotretinoin as they can cause a major flare of inflammatory spots at the start of treatment. The only way to deal with them is to lightly cauterise the skin above them using a hyfrecator

References

1. Bataille V, Snieder H, MacGregor AJ, Sasieni P, Spector TD. The influence of genetics and environmental factors in the pathogenesis of acne: a twin study of acne in women. J Invest Dermatol. 2002;119:1317-22.
2. Habeshian KA, Cohen BA. Current issues in treatment of acne vulgaris. Paediatrics 2020; 145:S225-S230
3. Collier CN; Harper JC; Cantrell WC et al. The prevalence of acne in adults 20 years and older. J Am Acad Dermatol. 2008; 58:56-9
4. Kircik LHJ. Advances in the understanding of the pathogenesis of inflammatory acne, Drugs Dermatol. 2016; 15:7S-10S
5. Mouser PE, Baker BS, Seaton ED, Chu AC. Propionibacterium acnes-reactive T helper-1 cells in the skin of patients with acne vulgaris. J Invest Dermatol. 2003;121(5):1226-8
6. Incidence and clinical importance of antibiotic drug resistance in Propionibacterium acnes in patients with acne on antibiotic therapy. Charikida A, Morris J, Chu A. Presented at 2nd Chinese-Anglo Dermatology Conference, Guangzhou, China 2004
7. Bottomley WW, Cunliffe. Oral trimethoprim as a third line antibiotic in the management of acne vulgaris. Dermatology. 1993;187:193-6
8. Pace WE. A benzoyl peroxide-sulfur cream for acne vulgaris. Can Med Assoc J. 1965; 93:252-234
9. Charikida A, Charikida M, Chu AC. Double blind randomised placebo controlled study of a lotion containing triethyl citrate and ethyl linoleate in the treatment of acne vulgaris. Br J Dermatol 2007; 157: 569-74.
10. Chamy JW, Choi JK, James WD. Spironolactone for treatment of acne in women, a retrospective study of 110 patients. Int J Womens Dermatol. 2017; 3:111-115
11. Hull PR, D’Arcy. Isotretinoin use and subsequent depression and suicide: presenting the evidence. Am J Clin Dermatol. 2003;4:493-505
12. Hogan C, Le Noury J, Healy D et al. One hundred and twenty cases of enduring sexual dysfunction following treatment. Int J Risk Saf Med. 2014;26:109-16.
13. Papageorgiou P. Katsambas A, Chu A. Phototherapy with blue (415nm) and red (660) light in the treatment of acne vulgaris. Br J Dermatol. 2000;142:973-8.
14. Seaton ED, Mouser PE, Charikida A, Alam S, Seldon PM, Chu AC. Investigation of the mechanism of action of nonablative pulsed-dye laser therapy in photorejuvination and inflammatory acne vulgaris. Br J Dermatol 2006; 155: 748-55
15. Seaton ED, Charakida A, Mouser P, Grace I, Clement RM, Chu AC. Pulsed-dye laser treatment for inflammatory acne vulgaris: randomised controlled trial. Lancet. 2003; 362:1347-52
16. Raone B, Veraldi S, Raboni R et al. Salicylic acid peel incorporating triethyl citrate and ethyl linoleate in the treatment of moderate acne: a new therapeutic approach, Dermatol Surg. 2013;39:1243-51
17. Eady EA, Cove JH, Holland KT et al. Recalcitrant acne vulgaris. Clinical, biochemical and microbiological investigation of patients not responding to antibiotic treatment. Br J Dermatol. 1988;118:415-23

Content provided by Anthony Chu, FRCP. Professor of Dermatology.

Vacuum erection devices and patient education for improved compliance - iMEDicare

iMEDicare Ltd have been distributing market leading medical devices within the fields of continence and andrology since being establishment in 2004. They firmly believe that patient education is the optimal route to achieve device user success and compliance. Their educational process comprises of unique one-to-one physical product guidance and expert fitting (5 cylinder size options “Size to Fit” concept, allowing for the patients’ anatomical needs and requirements to be encompassed in the assessment.

A popular product available from their portfolio is that of the SOMAerect Vacuum Erection Device (V.E.D.). The pump creates a vacuum inside the tube, which stimulates blood flow to the penis. Increased blood flow produces an erection. The perfect addition for penile rehabilitation and erectile dysfunction management: safe, consistent and cost effective.

What we know

The importance of the penile gym effect. Regular V.E.D. usage equates to a penile gym effect – oxygenation and mechano-receptor stimulation prevents dis-use atrophy (cavernosal fibrosis) and reverses penile shrinkage. (4)

Vacuum therapy also appears to be more cost-effective compared with frequent use of oral medications or frequent penile injections.

The British Society for Sexual Medicine Guidelines on the Management of Erectile Dysfunction in Men – 2017 recommends use of VED’s as a first line treatment response if lifestyle modification and PDE5 medication has not proved effective. They reference VED’s as being “Highly effective, regardless of ED aetiology”. (2, 6)

VEDs can also be “a useful adjunct to PDE5 /injection therapy post-RP, and to salvage treatment failures” VED therapeutic application post-prostatectomy is also well established and supported by the BSSM / MacMillan / PCUK.

The SOMAerect range of vacuum devices account for up to 80% of all schedule II VED prescriptions issued per annum in the UK (verifiable via published stats). The device is comprised Fully Customisable with 5-cylinder sizes (S / M / L / XL / XLL) and 4 erection maintenance ring types. Manual and Battery-operated versions. 92% Success Rate for ED (8% contraindicated or poor manual dexterity).

Figure 1: showing SOMAerect Vacuum Erection Device

Furthermore, vacuum therapy offers an opportunity for patients to return to sexual intimacy following pelvic surgery.

Figure 2: shows the outcome measures of intimacy using vacuum therapy following Radical Prostatectomy

How vital is product education?

Product education is a vital resource for patient understanding and most of all to improve product compliance (1). Studies have proven the use of a physical demonstration to improve Vacuum Erection Device efficacy from 40-60% up to 92% with similar improvements in 5 year compliance.

The main point to consider within a physical demonstration is customisation as we understand every patient is unique. Within the iMEDicare service we advise the options for the patients and advise the correct cylinder/ring sizing and type of pump dexterity dependent.

iMEDicare provide this clinical education service within a hospital setting run by product specialists. This entails a detailed tuition on device assembly / technique of usage both in a rehabilitative and intimacy context / safety limitations / device and components acquisition / trouble shooting service and on-going free technical support.

A recent study conducted by the Freeman hospital Urology department titled – ‘Erectile dysfunction after robotic radical prostatectomy: Real-life impact of vacuum erection device clinic’ (7). Discovered that following full tuition and support VED therapy is an effective treatment for men with post-RARP ED that is well tolerated with good short- to medium-term compliance. Up to two-thirds of men may find overall satisfaction with their post-RPED after VED therapy.

Figure 3 shows an accurate representation of patient compliance using vacuum therapy following attending an iMEDicare vacuum pump clinic.

Therefore, highlighting the importance of education and support to patients to ensure effective product outcomes.

Figure 3: Pie chart illustrating frequency of VED usage reported by survey respondents (%).

Should education be offered for other devices?

Education and guidance are both a fundamental part of a patients understanding for improved outcomes. Therefore, iMEDicare believes all individuals utilising patient home use product options should be offered step by step tuition for medical devices.

For instance, how about the use of reusable options within the incontinence management arena? Not only much more economical for the environment but extremely cost effective.

Wagg et al (2009) pointed out that the use of containment products such as pads or collecting devices is increasing every year due to the inconsistent delivery of continence care and the increasing demands of an aging population. (10)

Conclusion

This article emphasizes the purpose of patient understanding to ensure product compliance. After all, the type of training, support, and follow-up given to patients taking up is fundamental to their overall performance.

Easy to use products with good IFU’s and support training should be considered in comparison to (or indeed alongside with) expensive single use pharmacological aids (8,9). Detailed, individualised Patient education cements their understanding of the use and purpose of their device, resulting in improved satisfaction, clinical and social outcomes and ultimately improved compliance.

References

1. Mohiuddin, A. K. (2019). PATIENT EDUCATION: STEPS TOWARDS COMPLIANCE. Journal of Global Biosciences, 8(1), 5832-5846.
2. Lewis RW, Witherington R. External vacuum therapy for erectile dysfunction: use and results. World J Urol 1997; 15: 78–82.
3. Pahlajani, G., Raina, R., Jones, S., Ali, M. and Zippe, C., 2012. Vacuum erection devices revisited: its emerging role in the treatment of erectile dysfunction and early penile rehabilitation following prostate cancer therapy. The journal of sexual medicine, 9(4), pp.1182-1189.
4. Raina, R., Agarwal, A., Ausmundson, S., Lakin, M., Nandipati, K. C., Montague, D. K., ... & Zippe, C. D. (2006). Early use of vacuum constriction device following radical prostatectomy facilitates early sexual activity and potentially earlier return of erectile function. International journal of impotence research, 18(1), 77-81.
5. Madani, A., Watanabe, Y., Vassiliou, M.C., Fuchshuber, P., Jones, D.B., Schwaitzberg, S.D., Fried, G.M. and Feldman, L.S., 2016. Long-term knowledge retention following simulation-based training for electrosurgical safety: 1-year follow-up of a randomized controlled trial. Surgical endoscopy, 30(3), pp.1156-1163.
6. Hackett G et al. British Society for Sexual Medicine Guidelines on the Management of Erectile Dysfunction in Men – 2017. J Sex Med 2018;15:4305-7. Levine LA et al. Vacuum constriction and external erection devices in erectile dysfunction. Urol Clin North Am 2001;28:335-41.
7. Jones, P., Sandoval Barba, H., Johnson, M. I., Soomro, N., Robson, W., Ferguson, J., & Aning, J. J. (2020). Erectile dysfunction after robotic radical prostatectomy: Real-life impact of vacuum erection device clinic. Journal of Clinical Urology, 2051415820946630.
8. Phillips B, Zhao H. Predictors of assistive technology abandonment. Assist Technol 1993;5(1):36-45
9. McMillen A-M, Soderberg S. Disabled persons’ experience of dependence on assistive devices. Scandinavian Journal of Occupational Therapy 2002;(9):176-83.
10. Wagg A, Harari D, Husk J, et al (2010) The National Audit of Continence Care for Older People. Available at: www.rcplondon. ac.uk/projects/national-continence-audit- reports (accessed 11 February, 2015)

Content provided by iMEDicare.
For more information please visit www.mypelvichealth.co.uk.

Refuge - for woman and children. Against domestic violence.

For thousands of women and children across the UK, home is the most dangerous place to be during lockdown. Since March 2020, in what the UN called a ‘shadow pandemic’, reports of domestic abuse have increased in the wake of lockdowns around the world. The increased public understanding of domestic abuse during lockdown has also led to women recognising their partner’s behaviour as abusive for the first time. Domestic abuse is not just physical – it is a pattern of controlling, threatening and coercive behaviour that encompasses emotional, psychological, sexual and economic abuse. As awareness of the issue increases, so too does the number of women who recognise their relationship in other survivors’ stories.

Since March 2020, Refuge’s National Domestic Abuse Helpline saw a record increase in calls and contacts from women, their loved ones, and professionals in the sector. The increase in contacts peaked during the first lockdown in April, but remained high all year, increasing again during the November lockdown. Between April 2020 and February 2021, the National Domestic Abuse Helpline logged 61% more calls and contacts from women per month than during the baseline months of January-March 2020. Sadly, these are only the women who have reached out. We know that there are thousands more who have not yet asked for help, still trapped with their abuser.

Children living with violence in the home respond to their circumstances in many different ways. They may feel frightened, insecure and confused. Often, they learn to keep their feelings and fears to themselves – they may feel like the violence in their home life must be kept secret. With support, children can begin to cope with and make sense of what has happened in their families. They can overcome the trauma of witnessing or experiencing violence and go on to live safe, happy lives. Refuge believes that no child should have to live with fear or abuse. Our specialist staff understand the complex ways in which domestic violence can affect children. We can support them to rebuild their lives.

Perpetrators of violence against women and girls (VAWG) increasingly misuse technology by harassing, stalking, intimidating, impersonating, controlling and manipulating women and children. Usual solutions by state agencies include disconnecting the survivor from online accounts and devices, which compound the isolation for this vulnerable group and can lead to fear of technology.

Through frontline work with survivors of VAWG, Refuge identified trends around perpetrators’ use of technology, which included: installing ‘Spyware’ on mobile phones, hiding trackers in toys, tracking location via gaming consoles and online accounts, ‘revenge porn’, impersonation online, including credit card fraud, and harassment via Smart Home systems or relentless instant messages.

Ann’s* Story

Ann* came to Refuge three years after she separated from her abusive ex-partner. When they were together he had been psychologically abusive and used to gaslight Ann. He moved her car, and when she reported it as stolen and the police arrived, he implied it was her poor mental health at fault.

She was frustrated as she felt the perpetrator was continuing to have control over her and her four-year-old daughter, Ava*, who seemed very affected by his behaviour and the current child contact.

The abuser was taking her to court to enforce and change a child arrangement order. This was a continual behaviour pattern, taking her back to court every three months. She felt like she was constantly on eggshells with parenting and was very worried about going back to court, which she couldn’t afford.
The Refuge Advocacy team referred the case to Children’s Social Services due to ongoing concerns around the child contact. We also advocated to other professionals about the concerns around child contact, with Children and Family Court Advisory and Support Service (CAFCASS) becoming involved.

Delays in accessing legal aid were causing Ann distress. The Refuge Advocate liaised with the solicitor on her behalf, supported her to present evidence of the ongoing abuse to her solicitor, and attended hearings with her for emotional support.

Since engaging with Refuge, Ann now has legal representation, and CAFCASS is completing a report. The reports from professionals involved in the case were taken into consideration by the judge and child contact was reduced, while CAFCASS finish their report. This is what Ann had hoped for, and it has eased the stress on both her and Ava.

The case is ongoing and the next hearing is scheduled for early 2021.

*names changed to protect identity 

Content provided by Refuge. For more information please visit www.refuge.org.uk.