Clinical Snippets July 2023

The New Zealand General Practice Podcast

Dr Dave Maplesden and Dr Jo Scott-Jones

Shownotes

Clinical Snippets – July 2023 

1.  Superficial venous thrombosis (thrombophlebitis) 

(i)  After reviewing a recent case of death from pulmonary embolus in a patient seen a few days previously with an apparent lower limb SVT, I have reviewed HealthPathways guidance as follows.  Superficial venous thrombosis is usually a benign self-limiting condition, when it involves the smaller tributary veins in the lower limb or in the site of an existing varicose vein.  However, when the larger veins are involved (e.g. great and small saphenous veins) or when adjacent to the sapheno-femoral junction, there is risk of a DVT. A DVT may coexist at the time of diagnosis or the clot may extend to the deep veins within 10 days. 

(ii)   The risk for VTE is the highest immediately following a diagnosis of SVT but persists over time particularly in the first three months and decreasing but still significantly higher after five years.  Diagnosis is made by clinical findings, e.g. tenderness, induration, pain, or erythema along the course of a superficial vein.  D-dimer is not considered sensitive or specific enough to predict DVT in superficial venous thrombosis. 

(iii)  Arrange an ultrasound to exclude DVT if any of: 

• There is an involved segment of vein of 5 cm or more. 
• Either the great or the small saphenous vein is involved. 
• There is asymmetrical leg swelling. 

D-dimer is not considered sensitive or specific enough to predict DVT in superficial venous thrombosis. 

(iv)  Consider full oral anticoagulation for 3 months 3 if:   

• superficial venous thrombosis is within 3 cm of the sapheno-femoral junction and/or if the length of the superficial venous thrombosis is more than 5 cm. Also seek vascular surgery advice as ligation at the sapheno-femoral junction may be recommended. 
• other risk factors for DVT (e.g. an inpatient). Also seek haematology advice. 

(v)  If no risk factors, provide local symptom relief and prevent progression to a DVT: 

• Use pain relief, e.g. NSAIDs, for 8 to 12 days if not contraindicated. 
• Treat with elevation of the leg and compression stockings for comfort and to reduce swelling. 
• Only use antibiotics if signs of infection. 
• Encourage the patient to remain ambulatory. 
• Arrange follow-up at 7 to 10 days or earlier if there is deterioration. 

• If symptoms do not resolve, arrange or repeat the ultrasound. 

2.  ACE inhibitors and angio-oedema  

(i)  The Centre for Adverse Reactions Monitoring (CARM) recently received a report of fatal angioedema with an ACE inhibitor. The patient had experienced minor tongue swelling with an ACE inhibitor previously. A different ACE inhibitor was started at a later date, and the patient developed angioedema with a fatal outcome. 

(ii)   Before prescribing an ACE inhibitor, ask patients if they have taken these medicines before and if they had any adverse reactions. Specifically ask about swelling.  Inform patients who are starting ACE inhibitors about the symptoms of angioedema and advise them to seek urgent medical attention if these occur. 

(iii)  Visceral angioedema due to ACE inhibitors has been described in a handful of case reports and reviews. Most commonly, this presents as diffuse abdominal pain and diarrhoea. In more than one-half of the case reports of visceral angioedema, symptoms began within 72 hours of starting ACE inhibitor therapy, although in other reports, angioedema developed after weeks or years of therapy.  Diagnosis is often delayed. 

(iv)  ACE inhibitors should not be prescribed to patients with a history of ACE inhibitor-induced angioedema. Educate patients who have experienced ACE inhibitor-induced angioedema about the need to avoid all ACE inhibitors in the future.  NZF also advises against use of sacubitril-valsartan (Entresto) in these patients.   Most patients can be cautiously switched to an ARB.  A proportion of patients will have recurrence of angio-oedema after stopping the culprit ACE – most commonly within the first month.    

(v)  Angioedema is thought to occur in around 0.1% to 0.7% of patients who take an ACE inhibitor. Onset is usually during the first weeks or months of therapy, but it can occur years into treatment. Angioedema has also been reported with angiotensin II receptor blockers (ARBs; eg, candesartan, losartan), but the risk is thought to be lower than with ACE inhibitors. 

3.  Ivermectin Special Authority criteria amended 

The Special Authority criteria for ivermectin were recently amended (June, 2023). Any relevant practitioner can now complete the Special Authority form for ivermectin in patients with scabies and close contacts who meet Special Authority criteria. Discussion with a dermatologist, infectious diseases specialist or clinical microbiologist is no longer required. 

For information on the management of scabies, including the role of ivermectin, there is an excellent 2022 BPAC update on the topic.   

4. Allopurinol and variable adherence 

A recent NZ Doctor article on allopurinol  prescribing for the non-adherent included some timely reminders: 

• In a person who has become non-adherent to allopurinol (even for one month), do not automatically restart at a previous dose – re-titration is required.  Titration is dependent on renal function (see 2021 BPAC article for details).  Extra caution must be made with repeat prescribing of allopurinol and assuming a person is administering the last prescribed dose when they may not be. 

• The important point around dosing is to commence allopurinol according to renal function using clinical pathways or 1.5mg of allopurinol per eGFR unit as a guide. Note that renal function is used to guide starting doses, but once a person is stabilised on a dose of allopurinol, the dose should not be routinely decreased if renal function deteriorates. 

• Remember anti-inflammatory prophylaxis (and remember to stop this when stable).  This may be low dose NSAID or colchicine (or prednisone if alternatives not tolerated) 

• To mitigate treatment failure, people must be forewarned of the increased risk of flares when initiating allopurinol. It is also necessary to plan for the eventual cessation of anti-inflammatory prophylaxis. Usually, only three to six months is required, although this may be much longer in people with a high urate burden with tophi. 

• For patients with gout and hypertension, losartan or calcium channel blockers are the antihypertensive medicines of choice as they reportedly have mild uricosuric (urate-excreting) properties. Patients who are taking diuretics for hypertension, for reasons other than heart failure, should be switched to an alternative antihypertensive, if possible. 

• Always advise people that if a rash (especially extensive) occurs, they must cease allopurinol and seek medical assistance promptly.  Rash affects around 2% of people taking allopurinol but could be a symptom of allopurinol hypersensitivity syndrome (includes DRESS, Steven-Johnson syndrome and toxic epidermal necrolysis – affects about 1-4:1000 patients prescribed allopurinol and has a mortality rate of up to 27%). Risk factors for AHS include: higher starting dose of allopurinol and rapid titration; recent commencement (6-8 weeks) of allopurinol; coadministration of diuretics (especially thiazide) and amoxicillin; comorbidities of CKD and cardiovascular disease; risk of AHS is nearly 100-fold higher in carriers of the HLA-B*58:01 allele than in noncarriers. Populations with high allele frequency include people of Han Chinese (6%–8%), Korean (12%) and Thai (6%–8%) descent and NZF recommends genetic testing in these high-risk patients and avoiding allopurinol in confirmed carriers unless there is no suitable alternative.  See SaferRx for more details.   

• Māori and Pacific peoples are inequitably burdened by gout. There is also evidence demonstrating Māori and Pacific peoples are less likely to receive regular allopurinol prescriptions.  You can analyse your gout prescribing on the Epic dashboard in He Ako Hiringa including percentage of patients being prescribed urate lowering therapy irregularly, and there are tips for improving gout prescribing equity.    

5.  Topical anaesthesia for chronic painful leg ulcers 

Prilocaine-lidocaine (EMLA) cream has a listed indication of topical anaesthesia of leg ulcers to facilitate mechanical cleansing or debridement with instruction to apply under an occlusive dressing 30–60 minutes before procedure.  Cost:  Around $45 for the Numit brand (30g) from the Chemist warehouse.  The cream has also been studied as a primary dressing for painful leg ulcers and has proved effective.   

 The NZ Palliative Care Handbook also notes use of topical morphine as local pain relief for palliative patients with fungating wounds or ulcers with instructions:   morphine injection added to a gel in a clean environment and used topically may help (0.05 to 0.1% morphine [i.e. 0.5 to 1 mg/mL] in IntrasiteTM gel, metronidazole gel or KY JellyTM).  More detailed instructions including precautions are available as NHS guidance and note this is off-label use of morphine.   Some systemic absorption will occur, and it is most effective for superficial ulcers.  Some studies have shown reduced healing rates in wounds treated with topical morphine.   

6.  Dense breasts 

GP Research Review Issue 216  summarised a 2023 meta-analysis of MRI imaging in screening women at high risk of breast cancer which showed that  MRI alone increased the detection rate of breast cancer versus mammography alone by 8 per 1000 women screened while MRI plus mammography had a better detection rate versus MRI alone by 1 per 1000 women screened.  The article reviewer noted there is conflicting evidence of the impact of ionising radiation from repeated mammography related to repeated mammographic breast screening in women at high risk of malignancy and taking this into account MRI alone may be considered as best choice in such high-risk women. 

This raises the issues of informed choice and equity, particularly if private screening is the only way MRI imaging can be accessed in this situation.  The issue of reporting of breast density and management of women with extremely dense breasts within the Breast Screen Aotearoa (BSA) national screening programme is ongoing with formal reporting of breast density not currently part of BSA reporting requirements (see BSA information sheet) or planned as part of a recent quality improvement review of clinical quality and safety of the programme.  Discussion was stimulated following publication of European Society of Breast Imaging (EUSOBI) recommendations last year which included that women should be informed of their individual breast density and the diagnostic and prognostic implications of having dense breasts, and that supplemental or standalone MRI screening is offered to women with extremely dense breasts, from age 50-70, preferably every 2-3 years.    

7.  On a lighter note… 

Two more fascinating studies summarised in GP Research Review Issue 216 

1.  A randomized controlled trial on the effects of light music played by piano on satisfaction, anxiety, and pain in patients undergoing colonoscopy showed, in the group with piano music, significantly lower anxiety scores and higher overall satisfaction scores, including satisfaction with pain management, following the procedure than the group with no music.  The reviewer notes the results appear to be perfectly tailored to a GP’s waiting room – less anxiety, more satisfaction and less pain. And at no cost! Probably worth swapping the blaring radio ads/music in the waiting room for something soothing like Mozart. 

2.  A randomized trial on the effects of a topical hop extract gel versus topical oestradiol cream for treatment of postmenopausal sexual dysfunction showed no significant differences in the total Female Sexual Function Index (FSFI) or sub-scores (sexual desire, sexual arousal, vaginal lubrication, satisfaction, orgasm, sexual pain) between the two groups. There were no adverse events. Humulus lupulus L. (hop) has been recognised as having antioxidant, anti-inflammatory, anticancer, and oestrogenic properties.  I could not find any vaginal hop creams currently commercially available on line, and the hopeful sounding Tired Hands Hop Cream turned out to be a beer!