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ART OF MEDICINE

education

educationeducation

You can gain CPD points from your reading by recording what you have read in your appraisal folder. You should try to link your reading back to a learning need and also consider how you plan to improve your practice as a result of your learning. http://learning.bmj.com

CLINICAL UPDATES Preventing excess winter deaths and illnessesThe death rate increases in the UK during winter because of the direct effect of cold weather on the incidence of heart attacks, strokes, respiratory diseases, flu, and falls says NICE. A new set of six quality standards outlines a framework by which local authorities, commissioners, and healthcare providers should collaborate to prevent excess winter deaths. Hospital doctors should pay more attention to identifying patients who are vulnerable to health problems associated with cold homes. Such patients should have a discharge plan that includes ensuring that their home is warm enough.• http://bit.ly/1RjwpvC

Lack of ward beds and cancelled operations in WalesOperating theatres in Wales are not being used efficiently says a report from the general auditor for Wales, which states that a lack of ward beds is the most common reason for cancelled operations. These findings come after a Royal College of Surgeons report on the state of surgery in Wales, which found that waiting times were unacceptably long.• http://bit.ly/1T5ZfCk

Improved topical treatment for rosaceaIvermectin 10 mg/g cream significantly improves rosacea severity score and reduces lesion count compared with placebo. The mechanism of action remains unknown but is thought to involve anti-inflammatory effects and death of Demodex folliculorum mites. A Cochrane review evaluating treatment for mild to moderate papulopustular rosacea found that ivermectin cream shows slight superiority over topical metronidazole, although it has not yet been directly compared with azelaic acid. • http://bit.ly/1UMd8Fx

My most fortunate mistakeIt was my first day on call as a paediatric registrar and nearly my last—I missed a case of meningococcal disease. The departmental consultant took me to a toddler, saying, “This is the rash we see with meningococcal disease.” Emily had a fever (40°C) and widespread blanching rash. I knew that meningococcal disease presented with a petechial rash and was unimpressed. At the emergency doctor’s insistence I admitted Emily. A lumbar puncture was normal so I just observed her for 48 hours. Her fever settled, she remained well, and I sent her home.

The next day the laboratory said that Emily’s blood culture was growing Neisseria meningitidis. She was readmitted. Her repeat blood culture was sterile, but I gave her intravenous antibiotics for seven days, “just to be sure.”

My fascination with meningococcal disease began with Emily’s illness. How could she seem so well when other children were critically ill in 12 hours? She sparked off a case report, research fellowship, thesis, and career in paediatric infectious diseases. I have advised the Meningitis Research Foundation, the National Institute for Health and Care Excellence, and the Department of Health, and helped recommend meningococcal B vaccination for all UK children.

I learnt three valuable lessons from Emily: meningococcal disease can present with a blanching rash; lumbar puncture is normal in those with septicaemia, the more severe form of the disease; and if an experienced doctor tells you the diagnosis, s/he is probably right.Andrew Riordan, consultant in paediatric infectious diseases and immunology, Department of Paediatric Infectious Diseases and Immunology, Alder Hey Children’s Hospital NHS Foundation Trust, Liverpool, UKCite this as: BMJ 2015;350:h4588

We welcome contributions to this column via our online editorial office: https://mc.manuscriptcentral.com/bmj.

We print a statement on financial interests and patient partnership with each education article because they are important to us. We have resolved to reduce the involvement of authors with financial interests that The BMJ judge as relevant. We encourage and make clear how patients have been involved and shaped our content. More details can be found on thebmj.com.

Pulmonary rehabilitation is a programme of exercise, education, and psychosocial support for patients with chronic respiratory impairment. It aims to break the vicious circle of breathlessness that characterises many long term respiratory conditions.

Pulmonary rehabilitation is appropriate for patients who are

functionally limited by breathlessness (usually equivalent to Medical Research Council grade 3 or higher). It is highly cost effective and greatly improves health related quality of life, functional exercise capacity, and dyspnoea.• For more information visit BMJ Learning (http://ow.ly/ZR6rf)

FAST FACT—PULMONARY REHABILITATION

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10-MINUTE CONSULTATION

Pain at the back of the heelSarah Morton, Aisha Newth, Azeem Majeed

Department of Primary Care and Public Health, School of Public Health, Imperial College London, London Correspondence to: sarah.morton@doctors.org.ukThis is part of a series of occasional articles on common problems in primary care. The BMJ welcomes contributions from GPs.

A 41 year old man complains of longstanding pain at the back of his left heel and stiffness when he gets up. The pain is worse when he plays tennis. He asks for advice on what it is and what can be done.

Pain at the back of the heel arises from a limited number of anatomical structures: the Achilles tendon, the calcaneal bursa, or the surrounding soft tissues (fig 1). This limits the likely differential diagnoses. Achilles tendinopathy is the most common cause of posterior heel pain.1 Its incidence is estimated at 1.85 per 1000.2 It is also important to note that Achilles tendinopathy may underlie other pathologies, particularly partial tears of the Achilles tendon.3

What you should coverTake a historyBegin by understanding the pain: see table 1 and figure 1 for posterior heel pain differential diagnoses.

Ask about symptoms suggestive of inflammatory arthritis, such as ankylosing spondylitis.5 Comorbidities, such as type 2 diabetes and increased body mass index, are also associated with tendinopathy.2 6 Other biomechanical risk factors (which are likely to be modifiable) include decreased ankle dorsiflexion, pes planus, and increased hindfoot inversion.3 7

Review what medication the patient is taking because drugs can sometimes be associated with tendinopathy, including acute use of a quinolone and long term use of statins (mean time for onset of symptoms is 10 months).8 A family history of tendon problems can increase the risk up to five times.4

Examine the patientLie the patient prone. Look at and palpate the tendon. Note thickened tendons compared to the other side, which may indicate tendinopathy.3 5 Note tenderness,

WHAT YOU NEED TO KNOW

•  Achilles tendinopathy is the most common cause of chronic posterior heel pain

•  Achilles tendinopathy is a clinical diagnosis and imaging is not needed unless there is diagnostic uncertainty

•  Eccentric calf muscle exercises are traditional

and in particular pin-point tendon pain that makes a partial Achilles tear more likely. In retrocalcaneal bursitis there may be swelling and tenderness on direct palpation of the bursa.5

Establish if there is any crepitus present along the mid-portion of the Achilles tendon—again suggestive of Achilles tendinopathy.

Passively flex the foot to see whether the pain worsens on dorsiflexion or plantarflexion, to distinguish Achilles tendinopathy from posterior ankle impingement.4 Perform Simmonds’ squeeze test, palpate for a gap in the tendon structure, and observe if there is more dorsiflexion of the affected side to ensure there is no Achilles rupture.

Ask the patient to hop. If this reproduces the pain, it indicates Achilles tendinopathy.3

Overall there are no formalised criteria for diagnosing Achilles tendinopathy. It is a clinical diagnosis, and most of your information comes from the history.

What you should doRefer to the on-call orthopaedic team if an Achilles tendon rupture is suspected. If you suspect a tear, refer to a sports physician or orthopaedic team.

Consider an ultrasound scan if the diagnosis remains unclear to assess posterior ankle structures.4 Be aware that imaging may identify incidental, asymptomatic pathology such as tendinopathy on the non-painful side.

If Achilles tendinopathy is the working diagnosis, explain to the patient that symptoms may persist for up to two years despite treatment.4 Sedentary and active people may develop symptoms. Males and females are affected equally.2 It is most common between 41 and 60 years of age.2

The evidence on how best to manage this condition is poor and driven by opinion. The NICE clinical knowledge summary9 suggests that doctors might offer:•  Simple analgesia (such as non-steroidal anti-

inflammatory drugs for up to two weeks)•  Reduction in precipitating activities (complete rest

may make things worse).

0.5 CREDIT

HOW PATIENTS WERE INVOLVED IN THIS ARTICLEThis article predates our patient partnership initiative, so patient involvement was not requested

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Achilles tendon

Retro-calcaneal bursa

Subcutaneouscalcaneal bursa

Calcaneus(heel bone)

Fig 1 |  Anatomy of the heel

EDUCATION INTO PRACTICEDiscuss referral if there has been little improvement in symptoms of Achilles tendinopathy after 3-6 months.

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Consider a self directed daily programme of Achilles tendon strengthening exercises. There is little consensus over the type of exercises or the duration.9 Calf muscle eccentric exercises are the traditional first line exercises (see fig 2), but heavy slow resistance training, combining eccentric-concentric isotonic loading, may be as effective, with most participants having a significant decrease in pain and improvement in function after 12 weeks of conservative therapy.4-10 Eccentric exercises are easier to demonstrate to your patient. Advise your patient to wear shoes when doing the exercises and suggest online videos to aid with exercise technique, such as www.youtube.com/watch?v=M6EKuuZ7C2E. Referral to physiotherapy for biomechanical assessment and a more intensive exercise programme can be considered.9

Suggest rest from activities that exacerbate symptoms. Continue non-weight bearing activity, such as swimming, to maintain cardiovascular fitness. Use severity of symptoms to guide return to normal activities. If symptoms continue after 3-6 months despite the above measures, consider referral to a sports physician or orthopaedic surgeon.Competing interests: None declared.Cite this as: BMJ 2016;352:i1366Find this at: http://dx.doi.org/10.1136/bmj.i1366

Table 1 | Posterior heel pain differential diagnosesPathology Characteristic historyAchilles tendinopathy (mid-tendon)

• Chronic dull ache along the Achilles tendon• Pain classically 2-6 cm above the calcaneus• Gradual onset• Worsens with activity• Morning pain and stiffness are characteristic• Pain worsens on dorsiflexion3 4

Insertional Achilles tendinopathy

• Pain around the calcaneus

Retrocalcaneal bursitis • Pain between calcaneus and tendon• Tender to direct palpation at that particular point4 5

Posterior ankle impingement

• Pain worsens on plantar flexion5

Partial tear of Achilles tendon

• Sudden localised pain on background of longstanding pain in Achilles tendon3

Achilles tendon rupture

• Achilles tendon rupture is unlikely when a patient presents with chronic pain

Stand on the edge of a step with both feet. Use your good leg to rise on to tiptoes, transfer your weight to your bad leg (A), then lower yourself down (B). Perform three sets of 15 repetitions each twice a day

A B

Fig 2 | Performance of calf muscle eccentric exercise: unilateral heel drops (adapted from Nuffield Orthopaedic Centre. Achilles Tendinopathy: Advice and Management. 2009. www.ouh.nhs.uk/oxsport/information/documents/leaflet_achilles_a5.pdf)

FURTHER CLINICAL GUIDELINESOrthopaedic Section of the American Physical Therapy Association: www.jospt.org/doi/pdf/10.2519/jospt.2010.0305

EASILY MISSED?

Rheumatoid arthritisKate Harnden,1 Colin Pease,2 Andrew Jackson3

A 43 year old woman with six weeks of bilateral wrist pain is diagnosed with repetitive strain injury. Five weeks later, she returns with worsening pain. On further questioning, she reports increasing fatigue and two hours of morning stiffness in her hands. Examination reveals bilateral wrist and metacarpophalangeal joint swelling. She is referred to a rheumatologist, who diagnoses rheumatoid arthritis and initiates treatment.

What is rheumatoid arthritis?Rheumatoid arthritis is an autoimmune, polyarticular arthritis characterised by progressive joint destruction and deformity, usually of peripheral joints (box 1). Its cause is unknown, and extra-articular organ involvement such as interstitial lung disease and Sjögren’s syndrome may occur. Appropriate early therapy improves symptoms, function, and mortality, and may reduce comorbidities.

Why is it missed?Observational studies in England, Europe, and the United States all report delayed referral by general practitioners. A 2009 National Audit Office report found that patients in England with undiagnosed rheumatoid arthritis visited their general practitioner an average of four times before being referred; 18% visited over eight times.4 Detecting early rheumatoid arthritis is difficult as

1St James’ University Hospital, Leeds kateharnden@doctors.org.uk2Rheumatology, Chapel Allerton Hospital, Leeds3Bingley Medical Practice, Canalside Health Care Centre, Bingley This is one of a series of occasional articles highlighting conditions that may be more common than many doctors realise or may be missed at first presentation. The series advisers are Anthony Harnden, professor of primary care, Department of Primary Care Health Sciences, University of Oxford, and Richard Lehman, general practitioner, Banbury. To suggest a topic for this series, please email us at practice@bmj.com.

WHAT YOU NEED TO KNOW

•  Consider rheumatoid arthritis in any patient presenting with joint pain, swelling, and morning stiffness of over 30 minutes

•  Refer within two weeks if symptoms affect small joints of the hands or feet, or more than one joint, or have been present for at least three months

•  Starting treatment with combination disease-modifying antirheumatic drugs (including methotrexate), especially within three months of symptom onset, can slow disease progression and improve symptoms, function, and quality of life

•  When rheumatoid arthritis is suspected, x ray symptomatic joints and measure rheumatoid factor, erythrocyte sedimentation rate, and C reactive protein without delaying referral, as negative results do not exclude the diagnosis

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musculoskeletal problems are common in general practice. Clinical signs may be subtle, inflammatory markers such as erythrocyte sedimentation rate and C reactive protein are often normal, and more specific markers are also often negative (31% of patients are seronegative for rheumatoid factor and 33% are negative for anti-CCP (cyclic citrullinated peptide) antibodies).5

Why does it matter?The disability created by rheumatoid arthritis causes 28% of patients to give up their job within a year.6 There is a three month “therapeutic window of opportunity,” from symptom onset in which treatment can delay disease progression.7 Delaying treatment after this window has been shown to increase radiographic damage and mortality.7 8 Furthermore, a treatment delay of 3-6 months will make monotherapy less potent at inducing drug free remission.9

How is it diagnosed?Clinical featuresThe main symptoms are:•  Joint pain, swelling, and stiffness, commonly affecting

wrists, proximal interphalangeal, metacarpophalangeal, and metatarsophalangeal joints.

•  Early morning stiffness that lasts over 30 minutes (sensitivity 74-77%, specificity 48-52%10)

•  Systemic symptoms such as weight loss, fatigue (84% of patients at presentation in an observational study11) and malaise.

Features on examination include:•  Swelling of three or more joints (specificity of 73%12)•  Tenderness largely along the joint line•  Synovitis, producing a “boggy” or “doughy” swelling,

which may be subtle•  A positive “squeeze test”—pain on gently squeezing the

metacarpophalangeal or metatarsophalangeal joints together (fig 1) (sensitivity 40-48% but specificity 84% for early disease12).Synovitis of the wrist of flexor tendons may also present

with carpal tunnel symptoms such as pain and paraesthesia along the distribution of the median nerve.

Box 2 outlines the indications for referral.

InvestigationsIf rheumatoid arthritis is suspected, refer within two weeks to rheumatology and request the following blood tests without delaying referral: rheumatoid factor (69% sensitive and 85% specific5), erythrocyte sedimentation rate, and C reactive protein. If rheumatoid factor is negative, consider requesting a test for anti-CCP antibodies, which has similar sensitivity to rheumatoid factor (67%) but is more specific (95%).5 14

X ray the hands and feet if symptomatic without delaying referral, as erosive damage may be present, despite other investigations being normal. Ultrasound may be more sensitive for early synovitis, but its availability is limited in the UK.13 15

How is it managed?In the UK, early arthritis clinics have been set up to assess and treat patients with suspected rheumatoid arthritis.

Initial treatment involves offering a combination of disease-modifying antirheumatic drugs (methotrexate, sulphasalazine, etc) as soon as possible to slow disease progression and improve symptoms, function, and quality of life.13 Glucocorticoids, given intra-articularly, intramuscularly, or orally, provide quick, short term symptom relief and may slow joint damage. However, referring general practitioners should offer a glucocorticoid trial only if the patient is unlikely to be seen promptly in secondary care, as the drugs can make confirmatory diagnosis difficult. Annual review by general practitioners should include checking for and managing comorbidities such as cardiovascular disease, osteoporosis, and depression.13

Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: CP is treasurer of the British Society for Rheumatology; AJ is employed within a Federation owned community musculoskeletal service within sessions that he is paid for and he is a shareholder in profits made. Employed on an ad hoc basis as an RCGP musculoskeletal tutor.

Cite this as: BMJ 2016;352:i387Find this at: http://dx.doi.org/10.1136/bmj.i387

Box 1 | How common is rheumatoid arthritis?• In a 2010 systematic review, estimated prevalence in North America and

Northern Europe was between 0.5% and 1.1%. Developing countries have a lower prevalence (0.1-0.5%)1

• Rheumatoid arthritis is more common in women (3:1 female:male ratio).1 It can present at any age, but in a retrospective cohort study the mean age of onset was 55.6 years2

• The number of new cases identified in the UK each year is around 20 000.3 An average UK general practitioner will therefore see one new case every two years

A B

Squeeze test of (A) metacarpophalangeal and (B) metatarsophalangeal joints (adapted from Arthritis Research UK www.arthritisresearchuk.org/arthritis-information/inflammatory-arthritis-pathway/step-one.aspx)

Box 2 | When to refer (based on National Institute for Health and Care Excellence (NICE) guidance13)• Refer anyone with suspected persistent, unexplained synovitis to

rheumatology• Refer within two weeks if:

Small joints of the hands or feet are affectedMore than one joint is affectedAt least three months have elapsed between symptom onset and

presentation

HOW PATIENTS WERE INVOLVED IN THE CREATION OF THIS ARTICLEWe sought the opinion of a patient with rheumatoid arthritis, who described how her initial diagnostic process had been frustrating, with multiple visits to her general practice. She stated how essential a diagnosis had been in helping her manage and come to terms with the condition. Her comments about the importance of early diagnosis and appropriate management were taken into account when drafting the article.

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CLINICAL REVIEW

Facial cutaneous squamous cell carcinomaArif M Aslam, Anand N Patel

Nottingham NHS Treatment Centre, Queen’s Medical Centre Campus, Nottingham NG7 2FT, UK Correspondence to: a.aslam@doctors.org.ukThis is an edited version of the clinical review review, full version is on thebmj.com

1 CREDIT

Skin cancers account for almost half of all referrals to dermatology, and with an increasingly ageing population, in the United Kingdom non-melanoma skin cancers have been predicted to increase by 50% by 2030.1 Cutaneous squamous cell carcinoma (cSCC) is the second most common type of non-melanoma skin cancer after basal cell carcinoma (BCC). Its incidence is increasing worldwide and varies by geographical location.2 3

Primary cSCC is a malignant tumour of keratinocytes originating within the epidermis or its appendages that commonly occurs on sun exposed sites, mostly the head and neck.4 It can be locally invasive and has the potential to metastasise to regional lymph nodes.

This clinical review aims to provide an overview and will focus on the diagnosis and management of facial cSCCs.

Who gets cSCC?More than 80% of non-melanoma skin cancers occur in people aged 60 years or more.5 Incidence is highest in Australia—about 1035 cases per 100 000 men and 472 per 100 000 women.6 This increasing incidence is thought to be related to higher levels of sun exposure, an increase in the ageing population, increased sunbed use, and improved skin cancer detection.7 8

Table 1 lists the risk factors.

WHAT YOU NEED TO KNOW

•  cSCC is the second most common skin cancer after basal cell carcinoma and its incidence is rising. Ultraviolet radiation is the most important risk factor for developing cSCC

•  cSCCs usually occur on sun exposed sites, most commonly the ear, cheek, and nose

•  Organ transplant recipients have a greatly increased risk of developing cSCCs

•  High risk features include tumour size >2 cm, tumour depth >4 mm, location on the ear or lip, poor histological differentiation, perineural and lymphovascular invasion, and patient immunosuppression

•  Surgical excision with clear histological margins is the treatment of choice for most cSCCs; Mohs micrographic surgery is useful in high risk patients and at functional and cosmetic sites

What is the association between actinic keratoses and cSCC?Actinic keratosis (also known as solar keratosis) results from the proliferation of atypical epidermal keratinocytes. Its prevalence in the UK is reported as 19-25% in people over the age of 60.14

It often presents as erythematous scaly macules in adults with fair skin, and chronic sun exposure is a major risk factor.

It can be difficult to distinguish actinic keratosis from cSCC, and lesions that are tender, ulcerated, or rapidly growing should be biopsied for a definitive diagnosis.

The likelihood of progression of an individual lesion to cSCC is low and estimates of annual rates of transformation range from 0.03% to 20%.15-17 Nonetheless, study data suggest that about 65% of cSCCs arise from pre-existing actinic keratosis lesions.18

How do facial cSCCs present?Cutaneous SCCs commonly arise in areas of direct sun exposure, with a predilection for the head and neck (fig 1A-D). An analysis of the anatomical distribution in an Australian series of 1219 head and neck cSCCs showed the most common sites were the nose (20.0%), cheek and maxilla (19.8%), and ear (18.2%).19

The typical appearances are of a non-healing, usually progressively enlarging erythematous papule, plaque, or ulcer.20 In contrast to the typical pearlescent appearance and rolled edges of a BCC, the edges of a cSCC are usually everted. Lesions that are painful, grow rapidly, and bleed

Table 1 | Risk factors for developing cSCCRisk factor MechanismCumulative ultraviolet radiation exposure

Exposure causes pyrimidine dimer formation; this leads to point mutations in DNA, which if not repaired result in malignant transformation

Immunosuppression cSCC is the most common skin cancer in solid organ transplant recipients; this is secondary to the immunosuppressive therapy used to prevent transplant rejection, and the risk increases with time after transplantation. Incidence is 65 times higher than in the normal population; the tumours are more aggressive and occur mainly in sun exposed skin in areas of sun damage9

Chronic lymphocytic leukaemia

Multiple studies report that the relative risk of developing cSCC is 8.6 times that seen in the general population; it is a consequence of impaired host immune function10

Human papillomavirus (HPV)

HPV is a potential risk factor for cSCC but despite many studies the exact association remains unclear

Epidermolysis bullosa (EB)

Some forms of EB are associated with the development of cSCC, often at sites of chronic skin blistering, wounds, and scarring

Xeroderma pigmentosum (XP)

Patients with XP have about a 10 000-fold increased risk of non-melanoma skin cancer and a 2000-fold increased risk of melanoma under the age of 2011

Drugs Voriconazole is associated with photosensitivity and a dose dependent 2.6-fold increased risk of developing cSCC after lung transplantation12 Vemurafenib and dabrafenib are selective BRAF inhibitors that increase overall survival in metastatic melanoma. These drugs paradoxically activate the MAPK pathway in keratinocytes, resulting in cSCC, which often develops in the first three months of therapy. Older patients are at increased risk and tumours can occur in sun protected sites13

Chronic inflammatory conditions

The risk of cSCC is increased in chronically inflamed skin resulting from scars, burns, chronic ulcers, sinus tracts, or inflammatory dermatoses such as hypertrophic lichen planus and lichen sclerosus et atrophicus

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on contact are usually rapidly invasive and carry a higher risk of metastasis. Box 1 lists the red flags for cSCC and table 2 provides information on differential diagnoses that might present with similar features.

Keratoacanthomas (fig 2) are epithelial tumours that resemble cSCCs and tend to grow rapidly to form a crateriform nodule. Occasionally they spontaneously regress. They can be histologically difficult to distinguish from cSCC.

How is the diagnosis confirmed?In the early stages, clinically distinguishing cSCC from hypertrophic actinic keratosis can be difficult.

In people with a lesion suspicious of cSCC perform a full body skin examination, with particular attention to palpating the head and neck region for lymphadenopathy. Any history of excessive sun exposure and immunosuppression should be established.

Refer all patients with suspected cSCC to a hospital dermatology department where a diagnostic biopsy will be performed. A punch or incisional biopsy is usually performed and the biopsy must extend to at least the mid-reticular dermis. This enables assessment of perineural invasion, tumour differentiation, and tumour depth, information that is needed for tumour staging and prognosis.

What is high risk facial cSCC?High risk cSCCs exhibit clinical or histological features that are associated with an increased risk of aggressive tumour behaviour. Clinical and histopathological features that confer an increased risk of recurrence or metastasis have been proposed globally but there is no consensus. The American Joint Committee on Cancer (AJCC)21 and National Comprehensive Cancer Network (NCCN)22 have published guidelines on the assessment and classification of high risk cSCCs, which differentiate high and low risk tumours.

Box 2 lists the features of high risk cSCC.

What are the treatment options?Treatment aims to remove the tumour completely with minimal functional and cosmetic impairment. Treatment depends on tumour risk (box 2) and comorbidities.

The National Institute for Health and Care Excellence (NICE)24 recommends referring all confirmed cSCCs to

Fig 1 |  Different presentations of facial cSCC. (A) Below the right medial canthus, (B) left ear, (C) scalp with evidence of background photodamage, (D) nasal tip in a relatively young patient

Box 1 | Red flags for facial cSCCNew or changing lesion on the head or neck with any of the following features:• Slow growing scaly erythematous plaque• Hyperkeratotic indurated plaque• Painful, tender, eroded or ulcerated lesion• Rapidly growing crusted nodule

Fig 2 |  Large rapidly growing keratoacanthoma on the central scalp

Box 2 | Features associated with high risk cutaneous squamous cell carcinomas21‑23

• Tumour depth >4 mm and extension beyond the dermis or subcutaneous fat

• Located on the ear or lip• Immunosuppression• Perineural or lymphovascular invasion• Poor differentiation• Recurrent tumours

Table 2 | Differential diagnosis and distinguishing featuresDifferential diagnosis Distinguishing featuresHypertrophic actinic keratoses Flat, scaly and usually smaller than cSCCsSquamous cell carcinoma in situ (intraepidermal carcinoma)

Slow growing indolent asymptomatic patch or plaque with the absence of any red flags listed in box 1

Keratoacanthoma Rapidly growing with a shouldered and crateriform appearance; sometimes regress

Basal cell carcinoma Pearlescent telangiectatic lesion with rolled edgesInflamed seborrhoeic keratoses Pigmented lesions with a typical stuck on appearanceAtypical fibroxanthoma Slow growing asymptomatic firm red or pink papule or nodule, most

common on the head and neckMerkel cell carcinoma Rapidly growing painless, firm, non-tender, shiny skin coloured nodule

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the local skin multidisciplinary team.25 The team usually consists of dermatologists; pathologists; ophthalmologists; plastic surgeons; ear, nose, and throat surgeons; oncologists; radiologists; maxillofacial surgeons; general practitioners; and clinical nurse specialists.

Surgical excisionThe goal of surgical excision is to remove the tumour completely. This requires clearly identifiable tumour margins and can be difficult when the tumour is poorly defined (tumour edges indistinct). Tumour margins are identified histologically, and a predetermined margin of normal skin is also excised from around the tumour. The recommended margins are 4 mm for low risk tumours of <2 cm in diameter that have a well and easily demarcated border, and ≥6 mm for high risk tumours.

A systematic review of 12 observational studies that assessed tumour recurrence after surgical excision of invasive cSCC (1144 patients) found a local recurrence rate of 0-15% (pooled average rate 5.4%, 95% confidence interval 2.5% to 9.1%).26

Mohs micrographic surgeryMohs micrographic surgery (MMS), first described in the 1930s,27 provides a high cure rate with tissue conservation. Success rates are reported as 97% for primary cSCCs and 90-94% for recurrent tumours.28 During the procedure the tumour is excised and the margins colour coded. The excised fresh frozen tissue is sectioned horizontally and most of the surgical margins examined; with standard histological sectioning, <1% of the margin is visualised (fig 3A, B). If tumour is identified, further tissue is carefully removed

Fig 3 | (A) Periorbital cheek cutaneous squamous cell carcinoma on clinical examination. (B) Extensive area of invisible subclinical spread treated by Mohs micrographic surgery

Fig 4 |  (A) Large cutaneous squamous cell carcinoma of the central forehead. (B) The patient’s forehead three months after surgery showing an almost imperceptible scar

I first noticed a mark on my forehead during summer 2014. Within a month it had grown into a red bump that was slightly rough to the touch. I visited my GP and was told it was a subcutaneous wart that would be treated at the surgery by freezing. This took place in September, but by Christmas it had not gone and was beginning to enlarge. After a second visit to the GP I was referred to the hospital dermatology department.

I was seen by a consultant dermatologist and had a biopsy the next day. At a follow-up appointment I was told I had a squamous cell carcinoma and that I would need treatment (fig 4A).

My operation took place four weeks later and I returned twice during that week for a check and to remove the stitches. The days after the operation I was very swollen and covered with

bruising on my face—a friend said I looked like I’d done 10 rounds with Mike Tyson! The swelling and bruising went within a week, but I was left with a very tight feeling in my forehead. I also had a headache for most of the first week.

During the next few weeks the headaches subsided. The numbness in the forehead remained but it was not debilitating. The scarring also began to disappear but I was diligent at applying petroleum jelly at first and then oil, which was recommended by a friend.

Six months on and the scarring is hardly noticeable (fig 4B). I have very little numbness left—just a little at the top left of my forehead—but it was explained that this may take up to a year to subside. I see the consultant and clinical nurse specialist alternately every three months and will do for three years.

PATIENT PERSPECTIVE 1

from the precise site until complete clearance is achieved.

This technique is useful for high risk cSCCs and for lesions in cosmetically sensitive and functionally important sites (such as periocular sites). MMS is performed by specially trained dermatologists.

A 10 year Australian case series review of 1263 patients reported a 3.9% five year recurrence rate, with higher rates for recurrent tumours (5.9%) and those with perineural invasion (8%).29

Currently, no prospective randomised studies have compared therapeutic outcomes between conventional or wide surgical excision and MMS.

HOW PATIENTS WERE INVOLVED IN THE CREATION OF THIS ARTICLEWe asked two patients to provide a written personal account about their experience of cSCC and we discussed their ideas for the contents of this article. In particular we asked which areas the article should cover, and these were used as subheadings throughout the article.

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Currently, no prospective randomised studies have compared therapeutic outcomes between conventional or wide surgical excision and Mohs micrographic surgery

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RadiotherapyPrimary radiotherapy is an option for small well defined primary cSCCs. It is usually reserved for frail elderly patients who are not suitable for surgery. Outcomes are inferior to surgery with higher recurrence rates.

Adjuvant radiotherapy can be considered for patients with narrowly excised margins and those with perineural or lymphovascular invasion to minimise the risks of recurrence.

Other treatment optionsCurettage and cautery (electrodessiccation) involves scraping the skin with a blunt curette, which allows

friable tumour tissue to be delineated from surrounding normal tissues. It is not a conventional treatment in the UK but is occasionally used for well defined superficial low risk cSCCs on the extremities and trunk. It is not suitable for high risk cSCCs, but it is often used to treat the multiple eruptive keratoacanthomas and cSCCs associated with vemurafenib and dabrafenib. A disadvantage is the lack of adequate tissue to allow for margin analysis.

Other interventions such as cryotherapy, photodynamic therapy, and topical treatments such as fluorouracil and imiquimod have been reported, but because of insufficient evidence they should not be used for treating cSCC. These treatments are more commonly used for actinic keratoses or cSCC in situ.

In organ transplant recipients, data from prospective and retrospective pilot studies30 31 suggest that shorter duration of immunosuppression may reduce the rates of cSCC.

What is the prognosis for facial SCCs?For most patients the overall prognosis is excellent—an overall five year cure rate of >90% and overall metastasis rate of 2-5%.32

Extensive case series data have been used to investigate histological features of cSCCs—such as tumour diameter, depth of invasion, extension into subcutaneous tissue, poorly differentiated histology, and perineural involvement—that are associated with recurrence, metastasis, and death. Many studies have shown that tumours >2 cm in diameter have a high risk of metastasis, although other studies suggest 4 cm as a prognostic cut-off point. Poorly differentiated tumours have a 33% risk of metastasis, and immunosuppressed patients have a greater risk of developing metastases.23 33

After a primary cSCC, the estimated risk of any second non-melanoma skin cancer is about 50% at five years; the risk of another SCC is estimated to be 18% at three years and 30% at five years.34

How often should patients be followed up?Follow-up may not be needed in patients with low risk, well defined, completely excised cSCCs.

In the UK, it is recommended that patients with high risk cSCCs are reviewed by a dermatologist every three to six months for at least two years and up to five.4 25

Offer organ transplant recipients, people with multiple cSCCs, and patients who are immunosuppressed long term follow-up.

Each follow-up appointment should include a full skin examination with close inspection of the tumour site and examination of the regional lymph nodes.

Offer appropriate advice on sun protection and regular self skin examination at each visit (box 3). All patients should have access to a clinical nurse specialist for ongoing support.Cite this as: BMJ 2016;352:i1513Find this at: http://dx.doi.org/10.1136/bmj.i1513

Box 3 | Tips for patients on sun exposure, sunscreen, and self inspection• Advise patients to inspect and feel the surgical scar site,

local skin, and lymph nodes closely• Reduce ultraviolet exposure by wearing wear ultraviolet

protective sunglasses and a broad rimmed hat that protects the face, neck, and ears

• Do not to allow skin to become red or burnt• Avoid the sun between 10 am and 3 pm• Use high factor sunscreen to protect against ultraviolet A

and B• Apply sunscreen liberally 15-30 minutes before going out

and reapply every two hours and after swimming

PATIENT PERSPECTIVE 2I have had small pink scaly areas on my scalp for a long time and lost my hair in my 30s. I was told by my GP in the past that these were solar keratoses. However, after an area got worse so that I often caught it and made it bleed my GP referred me to the hospital. I was seen within two weeks and was told that it was suspicious for skin cancer. A biopsy was performed by a nurse on the same day. At my follow-up appointment three weeks later I was told it was an aggressive form of squamous cell carcinoma. I also have chronic lymphocytic leukaemia and sometimes need a blood transfusion. An operation was scheduled but by this time the area had grown quite large and I needed a split thickness graft from my right thigh. The operation was uneventful and I just about managed to cope, especially in the first week after surgery, but having the staples removed was not very pleasant. Nearly two months later I developed lots of small skin coloured spots over the rest of my scalp. One of these was biopsied and I was told that they were metastases from the cancer. I always seem to have lymph nodes in my neck area but my oncologist felt one on the right side that he thought seemed different to the others. I waited six weeks to see if this would disappear but it didn’t so I had a fine needle test with an ultrasound. Unfortunately this confirmed that the cancer had spread to my lymph glands and I’m now waiting to see the plastic surgeon and an oncologist who specialises in radiotherapy for skin cancer.

the bmj | 2 April 2016 41

ENDGAMES For long answers go to the Education channel on thebmj.com @BMJEndgames

answ

ers

CASE REVIEW Ongoing effects of burns1 Bilateral lower limb alkali chemical burns caused by exposure to caustic soda. The injury is circumferential and of heterogeneous depth.2 The burn was calculated to cover 9% of total body surface area (TBSA) using a Lund and Browder chart (5% and 4% on the right and left leg,

respectively). Depth varies, but most of the burn (8%) is superficial dermal to mid-dermal with 1% combined deep dermal and full thickness (leathery white).

3 Thermal (flame, contact, scald), chemical, electrical, and radiation related.4 Initially according to the advanced trauma life support algorithm. Using the parkland formula to calculate fluid resuscitation calculate TBSA

in step “E” (Exposure), taking care to prevent hypothermia. Give analgesia and tetanus prophylaxis if needed. Discuss with a burns unit or specialist. Check the pH of this alkali burn then irrigate with copious amounts of tepid water until pH neutralises.

SPOT DIAGNOSIS Fever in an injecting drug userThe computed tomogram shows multiple solid and cavitating lesions throughout both lung fields consistent with a diagnosis of pulmonary septic emboli from infective endocarditis. It also shows bilateral pleural effusions and consolidation.

CASE REVIEW Ongoing effects of burns

SPOT DIAGNOSISFever in an injecting drug userA 29 year old injecting drug user presented to the acute medical unit feeling generally unwell. On clinical examination he was found to be in septic shock with a fever of 39.2°C. A septic screen was performed and broad spectrum antibiotics started empirically. Staphylococcus aureus was grown in both blood culture bottles after one day. An echocardiogram showed a large irregular mass on the tricuspid valve. What complication does the computed tomogram of the thorax show?Submitted by Jennifer van Griethuysen and Simon W DubreyPatient consent obtained.Cite this as: BMJ 2016;352:i1137Find this at: http://dx.doi.org/10.1136/bmj.i1137

A 29 year old man presented with an isolated injury to both lower limbs after accidental spillage of caustic soda 20 hours earlier at a metal cleaning factory where he worked. Even though soaked protective clothing was removed at the time of exposure, a lack of irrigation of the area resulted in progressive development of skin changes (figs 1 and 2) and associated pain to the affected limbs. This prompted him to attend his local emergency department.1 What type of injury is this?2 What is the size and depth of the burn?3 What are the different types of burn?4 How would you manage this patient?Submitted by Karan Jolly, James Andrew Douglas, Nathan Hamnett, Ibrahim Natalwala, and William J C van NiekerkPatient consent obtained.Cite this as: BMJ 2016;352:i1104Find this at: http://dx.doi.org/10.1136/bmj.i1104

Fig 1 | Patient’s right leg Fig 2 | Patient’s left leg

A woman being treated for metastatic breast cancer with capecitabine was admitted with bloody diarrhoea. She developed an acute abdomen three days later. Contrast enhanced abdominal and chest computed tomography showed gas within the walls of the gastrointestinal tract, from the oesophagus to the large intestine, spreading into mesenteric and portal veins. This condition, pneumatosis intestinalis, is associated with various diseases, including pulmonary disease, autoimmune disorders, immunosuppression, and bowel

ischaemia, but can be an incidental finding. The most likely cause here was chemotherapy induced impaired mucosal integrity, which permitted gas forming bacteria to invade the bowel wall. She improved rapidly after starting antibiotics. Lisa Richters , Germany , De-Hua Chang , Norma Jung ( norma.jung@uk-koeln.de ) , Department I of Internal Medicine, University of Cologne, Germany Patient consent obtained. Cite this as: BMJ 2016;352:i277 Find this at: http://dx.doi.org/10.1136/bmj.i277

Pneumatosis intestinalis of the entire gastrointestinal tract

MINERVA A wry look at the world of research

Metformin and colon polyps

Metformin is a “teddy bear” drug, considered beyond criticism and good for many things. In Japan, 151 non-diabetic adults who had previously had single or multiple colorectal adenomas or polyps resected by endoscopy were randomised to low dose (250 mg) metformin or placebo ( Lancet Oncol doi:10.1016/S1470-2045(15)00565-3). There was a just signi� cant reduction in overall recurrence in the metformin group (risk ratio 0.67, 95% CI 0.47 to 0.97), suggesting that a long term cancer prevention trial might be worthwhile.

TOPCAT and HF-PEF TOPCAT was a trial of spironolactone for people with heart failure and preserved le� ventricular ejection fraction (HF-PEF); 1767 of the patients were recruited from North and South America and 1678 from Russia and Georgia. But a commentary on the trial ( JAMA Cardiol doi: 10.1001/jamacardio.2015.0356 ) � nds that event rates were 11.5% versus 2.4% per year in the � rst and second groups, respectively, suggesting that participating centres did not apply the same entry criteria. Importantly, respironolactone was e� ective in the large subgroup of patients from the Americas but not in the others.

Fortunately, a retrospective cohort study shows that it is easy to create a frailty index from routine electronic record data held in UK primary care ( Age Ageing doi: 10.1093/ageing/afw039). This can identify older people with mild, moderate, and severe frailty, with robust predictive validity for outcomes of mortality and hospital and nursing home admission.

Schizophrenia and suicidal thoughts Up to 40% of people with schizophrenia experience frequent suicidal ideation that persists or increases during the � rst years of treatment, according to a 10 year follow-up of the OPUS trial of young Danish patients with � rst episode psychosis ( Lancet Psychiatry doi: 10.1016/S2215-0366(15)00518-0 ). The investigators de� ne three di� erent trajectories for suicidal ideation and suggest that a focus on suicidal issues should be integrated into treatment.

Was Button gassed? When Jenson Button’s house was burgled in the south of France while he slept, the media reported that an anaesthetic agent had been used. This possibility was robustly denied by the Royal College of Anaesthetists on the grounds that it would require a “truckload” of anaesthetic agent. But Will Sellers calculates that sleepiness could be achieved with modest quantities of trilene or chloroform introduced into an air conditioning unit ( Br J Anaesth doi: 10.1093/bja/aew040 ). He warns that the criminal community might be interested in conducting further observational trials. Cite this as: BMJ 2016;352:i1725 Find this at: http://dx.doi.org/10.1136/bmj.i1725

Incalculable opioids Every palliative care formulary contains equivalence charts for commonly used opioids such as morphine, oxycodone, buprenorphine, and fentanyl, the bedrock of pain control in cancer. Two new studies examined how dosing is applied in clinical practice. In the � rst, Italian oncologists conducted a multicentre trial using these four drugs in 520 patients ( Ann Oncol doi: 10.1093/annonc/mdw097). Although they found similar patterns of e� cacy, frequent changes of dosage were needed and a considerable proportion of patients did not respond to speci� c opioids. The second study was an electronic survey of 319 physicians, pharmacists, and nurse practitioners in the US who were asked to calculate equianalgesic doses of opioids, including hydromorphone, methadone, and the four already mentioned ( Pain Med doi: 10.1111/pme.12920 ). Large variations in calculation were found in each professional group.

Procalcitonin in the ICU Intensive care units are full of people with rampaging bacterial infection, but it is essential to control antibiotic use to avoid breeding resistance. In a Dutch trial of 4507 critically ill patients with infections, procalcitonin monitoring was used to guide response to antibiotics ( Lancet Infect Dis doi: 10.1016/S1473-3099(16)00053-0 ). The monitored group was spared nearly two days’ worth of antibiotics compared with those treated according to clinical response, and they had lower mortality.

Frailty, thy name is electronic Frailty is a clinical buzzword for people with high vulnerability to physiological stress. Numerous frailty scores exist, but to be useful in clinical practice they have to be easy to generate and simple to use.

42 2 April 2016 | the bmj