Weight Loss with Periodic Fever Syndromes (FMF, TRAPS, CAPS) in South Africa

Overview of the Three Main Syndromes

Periodic Fever Syndromes in South Africa

FMF is the most common periodic fever syndrome globally and in South Africa. It is highly prevalent among Sephardic Jews, Armenians, Turks, and Arabs — communities present in Cape Town, Johannesburg, and Durban. However, MEFV mutations are increasingly recognised in other South African ethnic groups. TRAPS and CAPS are rarer but are diagnosed at tertiary centres. Genetic testing for MEFV, TNFRSF1A, and NLRP3 mutations is available through private molecular genetics laboratories in South Africa (R2,000-R5,000 per gene panel).

How Periodic Fevers Affect Body Weight and Composition

During Attacks: Acute Metabolic Stress

Each fever attack is a significant inflammatory and metabolic event:

• Fever increases basal metabolic rate by approximately 10-15% per degree Celsius — a 39-40°C fever for 2-3 days increases calorie expenditure substantially
• Nausea, vomiting, and abdominal pain (especially in FMF peritonitis) prevent adequate food intake during attacks
• Acute-phase protein synthesis (CRP, SAA, fibrinogen) diverts amino acids from muscle protein maintenance
• IL-1 and IL-6 surges drive anorexia — appetite suppression during fever is a direct cytokine effect
• After attacks: compensatory hyperphagia (excessive hunger) during recovery is common and can lead to rapid regain

Between Attacks: Chronic Sub-Inflammation

Even between clinical attacks, many patients with inadequately treated periodic fever syndromes have persistently elevated inflammatory markers (CRP, SAA). This chronic sub-inflammatory state:

• Drives insulin resistance independently of diet
• Promotes visceral fat accumulation
• Causes fatigue that reduces physical activity
• Increases cardiovascular risk over time

Long-Term: Secondary AA Amyloidosis

The most serious long-term complication of uncontrolled periodic fever syndromes — particularly FMF and TRAPS — is secondary AA amyloidosis, in which serum amyloid A (SAA) protein, chronically elevated during attacks, deposits as amyloid fibrils in the kidneys, leading to nephrotic syndrome and eventually renal failure. Nephrotic syndrome causes massive protein loss in urine (proteinuria), hypoalbuminaemia, oedema, and hyperlipidaemia — all of which profoundly affect nutritional status and weight.

Medication Interactions with Diet

Colchicine (FMF First-Line)

Colchicine is the cornerstone of FMF treatment — taken daily (0.5-2mg/day), it prevents attacks and dramatically reduces amyloid risk. Key dietary interactions:

• Grapefruit juice — inhibits CYP3A4 and P-gp, increasing colchicine blood levels and toxicity risk; avoid grapefruit entirely on colchicine
• High-fat meals — do not affect absorption significantly but high-fat diets increase cardiovascular risk which compounds with the chronic inflammation
• GI side effects — nausea, diarrhoea, and abdominal cramping are common at initiation; a low-fibre, easily digestible diet for the first 1-2 weeks eases tolerance. Gradually reintroduce fibre as the gut adapts
• Vitamin B12 — long-term colchicine reduces ileal absorption of vitamin B12; annual B12 testing is prudent; supplement if deficient
• Muscle toxicity — colchicine myopathy (rare at standard doses) is worsened by statin co-administration; if on both, monitor CK levels and report unexplained muscle pain

IL-1 Inhibitors (Anakinra, Canakinumab — TRAPS, CAPS, Refractory FMF)

• No significant food-drug interactions with anakinra or canakinumab
• Injection site reactions with anakinra — rotating sites; subcutaneous fat at abdomen or thigh; lean patients may have more discomfort
• Canakinumab is given every 4-8 weeks by injection (R80,000-R150,000/dose in SA private sector); funding through PMB for confirmed autoinflammatory disease; motivate with specialist letter
• Weight gain on biologics is reported but modest; more often, successful suppression of inflammation normalises appetite and metabolic function, and patients gain healthy weight if they were underweight from disease activity

Nutrition Strategy for Periodic Fever Syndromes

During Attacks: Priority is Fluid and Comfort

• Hydration is the immediate priority — fever increases water loss significantly; aim for 2-3 litres of fluid
• Oral rehydration if vomiting — mix 1 litre clean water, 6 level teaspoons sugar, half teaspoon salt (standard WHO ORS recipe)
• Easily digested carbohydrates — plain pap, soft cooked rice, toast, ripe banana
• Avoid high-fat, high-fibre, or spicy foods during attacks — they worsen nausea and abdominal symptoms
• Do not push calorie intake during an active fever; wait for fever to resolve before eating normally

Between Attacks: Rebuild and Optimise

The inter-attack period is where deliberate nutrition investment pays off. The goal is to:

• Replenish muscle protein lost during attacks
• Reduce background inflammation through dietary pattern
• Support kidney health (particularly important given amyloid risk)
• Maintain healthy body composition to buffer against the next attack

Anti-Inflammatory Dietary Foundation

• Mediterranean-style eating pattern — the highest-evidence anti-inflammatory diet; olive oil, fish, legumes, whole grains, vegetables, fruit
• Omega-3 fish — SA canned pilchards, mackerel, hake; 2-3 portions per week. Reduces IL-1 and IL-6 downstream signalling
• Rooibos tea — aspalathin is a genuine antioxidant; no caffeine, no drug interactions; make it a daily habit
• Turmeric and curcumin — small clinical data on IL-1 pathway modulation; cooking with turmeric (with black pepper for bioavailability) is safe and adds anti-inflammatory benefit to curries and stews
• Adequate protein: 1.3-1.6g/kg/day — prioritise during inter-attack periods to rebuild lean mass. Eggs, chicken, legumes, fish, low-fat amasi (maas)

Kidney Protection Nutrition (Amyloid Risk Reduction)

Given that AA amyloidosis is the key preventable complication of periodic fever syndromes, nutritional kidney protection is worth building in even before renal disease develops:

• Adequate hydration — 2 litres water daily; more in Highveld/Karoo summer heat
• Limit excess protein — over 2g/kg/day of protein puts unnecessary load on kidneys; stay in the 1.3-1.6g/kg range
• Low sodium — target under 2000mg/day; reduces blood pressure and renal workload
• No nephrotoxic supplements — avoid high-dose herbal supplements (kombucha in large amounts, high-dose vitamin C above 1000mg/day, aristolochic acid herbal products); many popular SA herbal health products have unverified nephrotoxic potential
• Annual urine dipstick and albumin-creatinine ratio — request from your GP as screening for early amyloid-related proteinuria

Exercise with Periodic Fever Syndromes

During Attacks: Rest

Exercise during an acute attack is contraindicated. The musculoskeletal and inflammatory burden during FMF, TRAPS, or CAPS flares is significant. Rest, hydration, and medication adherence take priority.

Between Attacks: Active Recovery

On effective treatment (colchicine for FMF; IL-1 inhibitors for TRAPS/CAPS), patients can and should exercise between attacks:

• Start with low-impact modalities — walking, swimming, cycling — and build up gradually
• Strength training 2-3 times per week helps rebuild lean mass lost during attacks and improves insulin sensitivity
• CAPS patients with cold-triggered urticaria (FCAS variant) should exercise in temperature-controlled environments; outdoor exercise in cold weather may trigger attacks
• TRAPS patients with migratory myalgia — residual muscle tenderness after attacks can persist; begin exercise gently and stop if pain significantly worsens
• Regular exercise reduces background IL-6 and CRP even in autoinflammatory conditions; a consistent exercise habit between attacks is one of the most effective inter-attack anti-inflammatory tools available

Managing Attack-Recovery Weight Cycles

The common weight pattern in periodic fever syndromes is loss during attacks followed by rapid regain (often above pre-attack weight) during recovery. To break this cycle:

• Maintain regular eating between attacks — consistent meal timing prevents the extreme hunger that drives post-attack overeating
• Prioritise protein at every inter-attack meal — blunts hunger and supports muscle repair
• Don't restrict aggressively between attacks — creating a calorie deficit between attacks compounds the muscle loss from the next attack
• Optimise treatment first — the single most effective weight-stabilisation tool is reducing attack frequency and severity through medication adherence (colchicine never stop without specialist guidance) and appropriate escalation to IL-1 biologics when needed

South African Resources and Support

• SARAA (South African Rheumatism and Arthritis Association) — saraa.org.za — periodic fever syndromes fall under rheumatology; SARAA has a specialist directory
• Inborn Errors of Immunity/Immunodeficiency SA — clinical immunologists at academic centres co-manage CAPS and complex TRAPS; Charlotte Maxeke and Red Cross Children's Hospital (Cape Town) have paediatric immunology experience with periodic fevers
• ADSA — adsa.org.za — registered dietitians for nutrition support around chronic disease
• Infevers database (infevers.eu) — international registry and mutation database for hereditary periodic fevers; your specialist may submit your case for guidance from the European network