One hot summer’s afternoon, 33-year-old single mum Janine comes to see you with her children. While normally energetic, today Janine isn’t her usual self and she winces in pain, reaching for something in her bag for one of the children.

Janine is concerned about a rash she has developed across the bridge of her nose and cheeks. She was sitting in the sun about two days ago and feels that it is probably just sunburn, though she didn’t seem to burn anywhere else, despite wearing a T-shirt and shorts. Janine also mentions that she’s had a fever for about week, though it hasn’t developed into anything, but thinks this is why she has been feeling very tired recently and has aching muscles, fingers and wrists in the morning. She tells you that she has noticed some painful ulcers on the roof of her mouth. Janine has no other medical problems, is of normal weight and smokes around 15 cigarettes a day.

On examination, you observe a flat, malar rash across her face and notice how it spares the nasolabial folds.

 

Based on the information provided, what is the most likely diagnosis?

  1. Sunburn
  2. Seborrheoic dermatitis
  3. Systemic lupus erythematosus
  4. Rosacea

Answer

The most likely diagnosis in this case is systemic lupus erythematosus (SLE), a chronic and multisystem, autoimmune connective tissue disease that affects around 1 in 1,000 people in the UK, primarily young women aged between 20 and 40.1 The disease follows a relapsing-remitting pattern, and in addition to cutaneous symptoms it affects cardiac, renal pulmonary and neurological systems. A cutaneous form of the disorder (without systemic involvement) is termed discoid erythematosis lupus.

While the rash may be due to sunburn, the absence of burning elsewhere makes this a less likely cause.

Seborrheoic dermatitis is associated with greasy scaling that occurs on the scalp and spreads to the face, affecting the eyebrows, nasolabial folds and the beard area. It is not associated with systemic symptoms. Moreover, the disease is more prevalent during the colder months of the year.

Although rosacea can be worsened by exposure to UV radiation, patients often complain of sensitive skin and burning or stinging sensation and telangiectasia are often visible on the cheeks. Furthermore, rosacea is not generally associated with mouth ulcers and systemic upset.

What features in the case history support your diagnosis?

  1. The fact that Janine smokes
  2. The presence of photosensitivity
  3. The presence of the malar rash
  4. The presence of mouth ulcers

Answer

In this case, answers 2, 3 and 4 when present potentially support the diagnosis of SLE based on a recent classification system,2 with photosensitivity being one of the most common symptoms.3 The malar (i.e. butterfly-like) rash is often precipitated by sunlight and presents as an erythematous rash over both cheeks and the nasal bridge sparing the nasolabial folds. According to Lupus UK, oral and nasal ulcers are commonly observed in up to 45% of those with SLE, often during a flare.4 While smoking per se is not diagnostic, research suggests that a history of smoking is modestly associated with development of SLE.5

In addition, approximately 90% of those with the SLE experience painful joints,6 particularly during periods of disease flare, and it seems possible that Janine is currently experiencing a flare, given her aches and pains.

Systemic lupus erythematosus is not a clinical diagnosis, and patients in whom the disease is suspected should have further investigations performed, such as FBC, renal and liver function, ESR, CRP and antinuclear antibody (ANA). A high ESR and normal CRP are characteristic of the disease. Although up to 95% of people with SLE test positive for ANA, the test is merely a screen when SLE is suspected and an ANA panel checking anti-dsDNA, anti-Smith, anti-Ro/SSA and anti-La/SSB.

What would be the most suitable course of action for this patient in this context?

  1. Belimumab
  2. Hydroxychloroquine
  3. Ustekinumab
  4. Referral to secondary care

Answer

The most appropriate first-line course of action would be referral to secondary care for confirmation of the diagnosis and advice on treatment.

Treatment recommendations for SLE are based on limited evidence from clinical trials. Nevertheless, antimalarials such as hydroxychloroquine (which is licensed for SLE) are recommended for all patients unless there are contra-indications.7 The drug is effective against arthritis and cutaneous symptoms and helps to maintain SLE in remission, but should be used based on the advice of a specialist. Nevertheless, recently it has been recommended that patients prescribed hydroxychloroquine (HCQ) and chloroquine for longer than 5 years undergo retinal screening due to an increased risk of hydroxychloroquine retinopathy.8

The biological agent belimumab was approved as an add-on therapy in SLE by NICE in 2016,9 but is reserved for patients with more severe disease and those unresponsive to standard treatment.

One recent placebo study suggests that the monoclonal antibody ustekinumab may be of value in treating patients with SLE,10 though its place in the management of the condition remains to be seen.

Outlook

According to recently introduced guidelines, Janine has mild SLE (malar rash, mouth ulcers and arthralgia).11 Initial management should include topical or oral corticosteroids (prednisolone up to 20mg daily), for 14 days to induce remission. She should also take hydroxychloroquine (6.5mg/kg/day) provided that she has normal renal and liver function.

There is good evidence that the malar rash can be significantly improved with HCQ after 3-4 months. Moreover, there is some evidence that HCQ reduces overall disease activities with reduced rates of flares and delayed time to renal damage.11 Janine also needs to use sun protection and should be advised about the use of sun-protective clothing. Though non-steroidal anti-inflammatory drugs (NSAIDs) can increase the risk of renal failure in patients with SLE, they can be used cautiously in patients to manage pain where paracetamol has been ineffective. Janine should have blood tests every one to three months during active disease and this can be reduced to 6 or 12 monthly once the disease is stable.

Monitoring is important, since between 20-75% of those with SLE will develop lupus nephritis, which leads to end-stage kidney disease in 10-17% of patients after 10 years.12

Despite the available interventions, patients in the UK with SLE will, on average, die 25 years earlier than the mean age for men and women.

References

  1. Walling HW, Sontheimer RD. Am J Clin Dermatol 2009. 10(6):366-374
  2. Anic F, Zuvic-Butorac M, Stimac D et al. Croat Med J 2014. 55(5): 514-19
  3. Scheinfeld N, Deleo VA. Photodermatolo Photoimmunol Photomed 2004. 20:272-79
  4. Costenbader KH, Kim DJ, Peerzada J et al. Arthritis Rheum 2004. 50(3):849-57
  5. Lupusuk.org.uk
  6. NICE. Prasterone for systemic lupus erythematosus. Draft scope. Available at: https://www.nice.org.uk/guidance/gid-tag373/documents/systemic-lupus-erythematosus-draft-scope2 [Last accessed November 2018]
  7. Kuhn A, Bonsmann G, Anders HJ. Dtsch Arztebl Int 2015. 112(25):423-32
  8. The Royal College of Ophthalmologists. Hydroxychloroquine and chloroquine retinopathy: recommendations on screening. February 2018. Available at: https://www.rcophth.ac.uk/wp-content/uploads/2018/07/Hydroxychloroquine-and-Chloroquine-Retinopathy-Screening-Guideline-Recommendations.pdf [Last accessed November 2018]
  9. NICE (TA397). nice.org.uk
  10. Van Vollenhoven R, Hahn B, Tsokos G et al. Lupus Science & Medicine 2018. 5(S1):S7A:8
  11. Gordon C et al. Rhematology 2018. 57:e1-e45
  12. Tunnicliffe DJ et al. Cochrane Database of systematic reviews 2018; 6: CD002922.

Rod Tucker

Pharmacist with a special interest in dermatology

 

Further reading: 

You’re the doctor: A photo-case study challenge