Monisha Gupta

Cardiovascular risk factors in women with primary Sjögren's syndrome: United Kingdom primary Sjögren's syndrome registry results

To determine the prevalence of traditional cardiovascular risk factors using established definitions in a large cohort of clinically well‐characterized primary Sjögrens syndrome (SS) patients and to compare them to healthy controls.

Psoriasis in those planning a family, pregnant or breast‐feeding. The Australasian Psoriasis Collaboration

The Australasian Psoriasis Collaboration has reviewed the evidence for managing moderate to severe psoriasis in those who are pregnant or are breast‐feeding, or planning a family. The severity of the psoriasis, associated comorbidities and specific anti‐psoriasis treatment, along with other exposures, can have a deleterious effect on pregnancy outcomes. Psoriasis itself increases the risk of preterm and low birthweight babies, along with spontaneous and induced abortions, but no specific birth defects have been otherwise demonstrated. The baseline risk for a live born baby to have a major birth defect is 3%, and significant neuro‐developmental problem is 5%. In Australia, pregnant women with psoriasis are more likely to be overweight or obese, depressed, or smoke in their first trimester, and are also less likely to take prenatal vitamins or supplements. Preconception counselling to improve maternal, pregnancy and baby health is therefore strongly encouraged. The topical and systemic therapies commonly used in psoriasis are each discussed separately, with regards to pregnancy exposure, breast‐feeding and effects on male fertility and mutagenicity. The systemic therapies included are acitretin, adalimumab, apremilast, certolizumab, ciclosporin, etanercept, infliximab, ixekizumab, methotrexate, NBUVB, prednisone, PUVA, secukinumab and ustekinumab. The topical therapies include dithranol (anthralin), calcipotriol, coal tar, corticosteroids (weak, potent and super‐potent), moisturisers, salicylic acid, tacrolimus, and tazarotene. As a general recommendation, effective drugs that have been widely used for years are preferable to newer alternatives with less foetal safety data. It is equally important to evaluate the risks of not treating, as severe untreated disease may negatively impact both mother and the foetus.

The Australasian Psoriasis Collaboration view on methotrexate for psoriasis in the Australasian setting.

The Australasian Psoriasis Collaboration reviewed methotrexate (MTX) in the management of psoriasis in the Australian and New Zealand setting. The following comments are based on expert opinion and a literature review. Low‐dose MTX (< 0.4 mg/kg per week) has a slow onset of action and has moderate to good efficacy, together with an acceptable safety profile. The mechanism of action is anti‐inflammatory, rather than immunosuppressive. For pretreatment, consider testing full blood count (FBC), liver and renal function, non‐fasting lipids, hepatitis serology, HbA1c and glucose. Body mass index and abdominal circumference should also be measured. Optional investigations in at‐risk groups include an HIV test, a QuantiFERON‐TB Gold test and a chest X‐ray. In patients without complications, repeat the FBC at 2–4 weeks, then every 3–6 months and the liver/renal function test at 3 months and then every 6 months. There is little evidence that a MTX test dose is of value. Low‐dose MTX rarely causes clinically significant hepatotoxicity in psoriasis. Most treatment‐emergent liver toxicity is related to underlying metabolic syndrome and non‐alcoholic fatty liver disease or non‐alcoholic steatohepatitis. Alcohol itself is not contraindicated, but should be limited to < 20 gm/day. [Correction added on 6 January 2017, after first online publication: ‘20 mg/day’ has been corrected to ‘20 gm/day’.] Although MTX is a potential teratogen post‐conception, there is little evidence for this pre‐conception. MTX does not affect the quality of sperm. There is no evidence that MTX reduces healing, so there is no specific need to stop MTX peri‐surgery. MTX may be used in combination with cyclosporine, acitretin, prednisone and anti‐tumour necrosis factor biologics.

Psoriasis and infection. A clinical practice narrative

The Australasian Psoriasis Collaboration has developed a clinical practice narrative with respect to the relationship between psoriasis, its treatment and infection. The cutaneous microbiome of patients with psoriasis is different to those without psoriasis, although the significance of this is unclear. Whilst a wide range of microorganisms has been associated with psoriasis (including β‐haemolytic streptococci, Staphylococcus aureus, Porphyromonas gingivalis, Candida albicans, Chlamydia psittaci, human immunodeficiency virus and hepatitis C virus), there is limited evidence that antimicrobial therapy is of direct benefit in preventing flares of psoriasis. Psoriasis is independently associated with an increased risk of serious infection, but the absolute risk is low. The risk of serious infections is further increased with immune‐modulatory treatments. The decision whether to, and when to, stop or resume immune‐modulatory treatment after a serious infection has occurred depends on risk assessment for that patient, taking into account the infection being treated, the risk of recurrent infection, any interventions that can modify the risk and the need for psoriasis control. Live vaccines (e.g. MMR, varicella, zoster and yellow fever) are generally contraindicated in patients with psoriasis on immune‐modulatory agents, but this depends on the degree of immune suppression and individual risk factors. Wound healing in psoriasis is normal. Treatment with infliximab, adalimumab, etanercept, methotrexate and ciclosporin can safely be continued through low‐risk surgical procedures. For moderate‐ and high‐risk surgeries, a case‐by‐case approach should be taken based on the patients individual risk factors and comorbidities.

Psoriasis and cancer. An Australian/New Zealand narrative

Patients with psoriasis have an increased risk of cancer, which may be due to impaired immune surveillance, immune modulatory treatments, chronic inflammation and/or co‐risk factors such as obesity. The increase in treatment‐independent solid cancers, including urinary/bladder cancers, oropharynx/larynx, liver/gallbladder and colon/rectal cancers, seem to be linked to alcohol and smoking. Lung cancer and nonmelanoma skin cancer are also increased in patients with psoriasis. The risk of nonmelanoma skin cancer increases with age and severity of psoriasis. It is also higher in men, particularly for squamous cell carcinoma, which may reflect previous exposure to PUVA and/or ciclosporin. The risk of cutaneous T‐cell lymphoma is substantially higher in patients with moderate‐to‐severe psoriasis. Biologic therapies are independently associated with a slight increase risk of cancer, but this is less than ciclosporin, with the risk confounded by disease severity and other co‐risk factors. The risk of cancer from low‐dose methotrexate is likely minimal. In contrast, acitretin is likely protective against a variety of solid and haematological malignancies. The data on small molecule therapies such as apremilast are too immature for comment, although no signal has yet been identified. The decision whether to stop psoriasis immune modulatory treatments following a diagnosis of cancer, and when to resume, needs to be considered in the context of the patients’ specific cancer. However, there is no absolute need to stop any treatment other than possibly ciclosporin, unless there is a concern over an increased risk of serious infection or drug–drug interaction with cancer‐directed therapies, including radiotherapy.

Leishmania tropica successfully treated with photodynamic therapy

Cutaneous leishmaniasis is a neglected tropical infection that inflicts significant morbidity and disfigurement. In Australia it is seen in migrants and returned travellers from endemic areas. Photodynamic therapy is indicated for the treatment of selected non-melanoma skin cancers and premalignant lesions. However, it has also been successful as an alternative off-label therapy for the management of cutaneous leishmaniasis. We present the case of an otherwise well 29-year-old man from Pakistan who presented with a rapidly expanding exophytic and crusted plaque on the dorsum of the nose extending into the distal nares (Fig. 1a). Three months before migrating to Australia he noted an erythematous papule, which he attributed to an insect bite, that enlarged rapidly. His most significant concern was social embarrassment and stigma in the context of his new job working in customer service. A punch biopsy was performed that confirmed a clinical diagnosis of cutaneous leishmaniasis. He received 3 weeks of oral fluconazole (200 mg daily) with no change, and hence was referred to the local tertiary dermatology service for consideration of alternative management strategies. The punch biopsy demonstrated granulomatous inflammation, with admixed neutrophils occupying the full thickness of the dermis. Numerous parasitised histiocytes were noted in the superficial dermis, consistent with leishmaniasis. A polymerase chain reaction test of the tissue confirmed it was Leishmania tropica, a subspecies of Old World cutaneous leishmaniasis. Cutaneous infection caused by L. tropica is recognised as a self-healing condition. However, due to the cosmetically sensitive site and considerable morbidity from this condition, treatment was considered. Intralesional antimonial therapy is recommended, however it is not uniformly available in Australia. Further, due to the failure of azole medications, photodynamic therapy was chosen to be trialled. Photodynamic therapy was administered approximately weekly (range 6–8 days due to availability), as per the treatment interval used by other case series of this treatment modality. The adherent crust was removed with gentle curettage, a 1-mm thick layer of methyl aminolevulinate (16% cream) was applied to the affected area along with a 5-mm margin and then occluded for 3 h, following which 8 min of continuous 630-nm red light was directed at the area. Paracetamol (1 g) was given prior to the procedure and it was tolerated well. At the first review (day 8), a dramatic improvement was seen (Fig. 1b). Prior to the fourth and final treatment, the patient’s skin had almost completely normalised (Fig. 1c) and he was satisfied with the outcome. To maximise inflammation and thus eradicate the amastigotes and to reduce the risk of recurrence, a further three photodynamic therapy sessions were performed at weekly intervals, in accordance with previously effective regimens, with an exceptionally good cosmetic outcome. After the photodynamic therapy sessions the patient was lost to follow up and could not be contacted. Apart from antimonials and azoles, other local therapies, including topical agents and physical therapies such as cryotherapy and radiofrequency-induced heat therapy, may limit the need for systemic treatment and maximise cosmetic results but can be less efficacious and have a higher risk of recurrence. While the mechanism of photodynamic therapy in the treatment of leishmaniasis is yet to be elucidated, there is evolving evidence that a systemic immunomodulatory response is responsible for the clearance of cutaneous