Skin complications of systemic diseases are common in general practice, as diseases in every organ system can have skin symptoms. Additionally, the majority of the systemic medications used in the treatment of various conditions have a list of potential side effects involving the skin, for example, rashes, pruritus and urticaria. Alternatively, they might exacerbate existing skin conditions, for example, live vaccines for shingles or beta-blockers for psoriasis.
Patients presenting with skin conditions represent 24% of all GP appointments requiring medical intervention (Schofield et al, 2011). It is particularly difficult for patients to come to terms with a skin condition, as the majority of treatments are topical applications of leave-on medication, leading to considerable discomfort. Further, one of the main symptoms of most skin conditions—itching as well as the reaction of scratching—can be very distressing as it can take over the patient's life, leading to loss of sleep and detrimentally affecting quality of life.
This article aims to improve awareness of skin manifestations of systemic conditions by describing one common and two rare ones in the general population, and it guides healthcare practitioners on how they can monitor and support patients with these skin conditions.
Pruritus
Pruritis is defined as the desire to scratch, and it can occur as a common feature of a skin condition, but also can present as generalised pruritus with no rash or previous history of skin disease, especially in older adults. In these cases, it is important to ask if there had been any childhood eczema, and then investigations are required to exclude an underlying systemic disorder. Pruritus can lead to scratching and the resulting damage of excoriations and lichenificaton (thickening of the epidermis), which can change the physical presentation of the skin and in turn hinder diagnosis, for example, scabies or eczema/psoriasis (Figure 2). If a person has taken corticosteroids over their lifetime, for example, for asthma or arthritis, they might have accumulative thinning of the epidermis and dermis, with bruising and purpura. In such cases, the resulting damage from scratching would be all the more dramatic in appearance and thus more distressing for the patient. Especially for patients on anticoagulants, more trauma occurs through scratching—for example, extensive bruising or surface bleeds/tears to the skin—and these can make the condition appear more distressing for the patient and their family.
History-taking should include detailed information about all medication administered, including prescribed and over-the-counter (OTC) medicines or those borrowed from friends. Itch is a common side effect of many drugs, but prescribed medication should only be stopped on the advice of a health professional. It may resolve on stopping the systemic medication or if an alternative medication is prescribed, but if the systemic condition remains uncontrolled with the change in regimen, then the previous medication might have to be resumed, with the patient having to accept the side effect of pruritus. If patients have a poorly controlled condition, for example, hyperthyroidism or hypothyroidism, or poor concordance with prescribed medication (Healy and Sahota, 2007), then they may present with pruritus. Further, generalised pruritus is known to be a symptom of primary biliary cirrhosis and can be apparent in those with extrahepatic obstruction. About 25% of patients with chronic renal disease and 86% of those on haemodialysis present with pruritis despite topical therapy, and this skin manifestation is only eventually resolved after a successful renal transplant (Healy and Sahota, 2007).
Management
First-line treatment for pruritis involves the introduction of soap substitutes and leave-on emollient therapy to circumvent the use of OTC products that can cause irritation to the skin and strip the skin of its natural oils, causing further dryness and itching. It is important that the patients be educated on how to use these products. Smooth downward strokes should be used to apply them directly onto the skin, as this method prevents skin irritation; additionally, skin pores could become blocked if the product is rubbed on, or it could become overheated if the product is applied too thickly, which exacerbates the pruritis. Education is also important, because it is difficult for patients to change their behaviour and accept the need to apply products throughout the day or find the time to carry out the skin care.
Patients must also ensure that they keep water temperature low while bathing, as this prevents further dryness through evaporation and, consequently, itching. The choice of leave-on emollient depends greatly on the patient's comfort with the sensation of having this product on their skin, and their clinical needs (Peters, 2019). Products are available in various forms, including sprays, lotions, gels, creams and ointments, and they are usually composed of a mixture of oils and water with additives like humectants (urea), which can help trap water in the epidermal layer.
Second-line treatment may involve the use of sedating antihistamines to relieve the symptom of itching. For neuropathic itch, the use of oral doxepin or amitriptyline has been found to be effective (Ryder and Stannard, 2005). However, non-sedating antihistamines are not very effective in relieving itch, and the lack of sleep can exacerbate pruritus.
Cardiovascular disease and inflammatory dermatosis
There is a well-recognised link between psoriasis or inflammatory dermatosis and cardiovascular disease, and the National Institute for Health and Care Excellence (NICE) (2012) psoriasis guidance has placed an emphasis on discussing general health and fitness with patients with cardiovascular disease, along with body mass index and cholesterol. Additionally, the guidance recommends the use of a risk assessment tool (Q risk or Framingham score) in primary care when patients start taking certain systemic medications (methotrexate, tacrolimus, acitretin), as the finding of these tools can predict the possibility of psoriasis.
There has been much discussion around disease process versus lifestyle, including alcohol intake and smoking behaviour, in the development of cardiovascular disease in patients with psoriasis. It can be very uncomfortable and embarrassing to exercise with sore, flaky skin. While lifestyle undoubtedly plays a part, research indicates that the inflammatory changes themselves lead to an increase cardiovascular risk in patients with severe psoriasis (Penzer-Hick, 2019). A recent study also demonstrated such an association between severe atopic eczema in adulthood and all forms of non-fatal cardiovascular disease (Silverwood et al, 2018).
Management
Individuals with severe atopic eczema who have received systemic immunosuppressant medication or phototherapy are defined as being at risk, and they should be referred to secondary care, for assessment of the indicators of disease severity as well as the risk of stroke, unstable angina, atrial fibrillation, myocardial infarction and heart failure and death from cardiovascular disease.
All adult patients with severe psoriasis or atopic eczema should be recommended to seek advice for cardiovascular disease prevention and be treated with medication for the latter, if required, in order to improve their health outcomes.
Skin cancer in transplant patients
Under the partially updated guidance from NICE (2010) for improving the outcomes for people with skin tumours, those who have had a kidney transplant should be screened for skin cancers every year. This is because they are taking immunosuppressants such as azathioprine or calcineurin inhibitors (tacrolimus), which increase their susceptibility to sun damage and tumour growth in comparison to mycophenolate mofetil or rapamycin. Immunosuppressant drugs hamper the self-repairing ability of DNA, because of which skin exposed to UV rays in sunlight cannot repair itself. These drugs also prevent the immune system from attacking the donated organ as a foreign body, thus allowing the body to better accept it.
In fact, all patients who have had a solid-organ transplant (e.g. heart, lung, pancreas and liver) have a much higher risk of skin cancers compared to those in the general population (Gerlini et al, 2005). Squamous cell carcinoma, which is the second most common skin cancer, occurs 65–250 times more often in transplant patients than in the general population (Krynitz et al, 2013). Similarly, melanoma occurs 6–8 times more frequently (Jensen et al, 1999) in transplant patients, and basal cell carcinoma is also more common in these individuals. O'Gorman and Murphy (2019) have written a very useful review of the cancer risk potential of organ transplantation. As always, it is a balance of risk versus benefit, as waiting for an organ transplant can be very challenging. Other factors to consider include how long the patient has been immunosuppressed, age, gender, human papilloma virus infection, genetic predisposition or lighter skin colour (red headed or Celtic) and UV over-sensitivity (O'Gorman and Murphy, 2019).
Management
Transplant patients should undergo a full skin surveillance and lymph node examination on an annual basis conducted either by doctors, skin cancer nurse specialists or dermatology nurse specialists with advanced skills and knowledge. This should involve the use of a dermoscope, and patients may need to be referred to a dermatology surgery or plastic surgeon. Health promotion should be supported in primary care, with information and re-enforcement regarding safe behaviour in the sun, and in case of concerns in between annual reviews, lesion reviews are essential, with referral to dermatology if required.
Conclusion
This article illustrates the close association between the skin and systemic organs, highlighting that skin diseases are not merely superficial and should be taken seriously as they may indicate a systemic problem. Older people, many of whom live alone, may be less adaptable to the introduction of skin care. Further, they may not have the dexterity needed to carry out topical skin care, so access to personal care may need to be signposted for them if they are to meet the health professional's expectations of managing their skin condition.