My Fingers are Blue: Benign or Worrisome? Joke Dehoorne, dienst kinderreumatologie, UZ Gent Kinderartsenvergadering 21/2/2017
Aim Work up and referral of a child/teenager with discolored fingers Distinguish between benign digital color changes, and those more concerning for a larger disease process
Case 1 14-y, white female: 2-year history of painless intermittent purple/blue discoloration and coolness of her hands bilaterally duration: 1-2 weeks, 3 or 4 times per year, always in winter triggers- fever-, weight loss-, diarrhea-, triphasic color changes- medical history: incontinence (oxybutynin)
Case 1: physical exam W: 53 kg; H: 173 cm; BMI: 18 kg/m 2 (25 th percentile) Purple, red, cold fingers ( 3-sec capillary refill), cool cyanotic toes ( 4-sec capillary refill)
Case 1 lab: CRP-, ESR-, PBC nl, ANA normal nailfold capillaries symptomatic treatment, heated gloves 3 months later, the patient reported no additional episodes of pain and swelling
Case 2 7 y whitegirl pain in hands while washing dishes ulcerationfingertip+ painfulcoldsensations+ reversible color changes in the fingers symptoms: writing, exposed to cold feet onset of symptoms: 3 months before the visit family history: similar symptoms-, autoimmune disease-
Case 2: clinical examination swollen hands, healing ulceration
Case 2 Progressive thickening and tightening of the skin around her fingers, hands, forearms, lower limbs and feet. Face and trunk were spared. Flexion deformities of all fingers with finger tip ulcerations, pittig scars and pulp space wasting Dilated capillaries of the nail fold
Case 2: investigations PBO, serum chemistry (e.g. serum total protein and albumin, electrolytes, liver and kidney function, muscle enzymes and acute phase reactants) and urine analysis: normal except for the LDH (831 U/L), ESR (61 mm/hr). IgG: 23 g/l (7-16) IgA, IgM and C3, C4, CH50 normal
Case 2: investigations Autoimmune serology: ANA: speckled 1/640 anti-ds DNA - Anti-ENA: anti-rnp -, anti-sm -, anti-histone-, anti- SS-A (Ro)-, anti-ss-b (La) -, anti-centromere-, anti- SCL 70 + antiphospholipid Ab Nail fold capillaroscopy: tortuous dilated capillaries, giants with dropouts
Case 2 diagnosis: juvenile systemic sclerosis (jssc)
Episodic Cold Blue Fingers Differential diagnosis (most common to least common) Benign Acrocrocyanosis Raynaud s phenomenon Chillblains= Pernio (Frostbite) (Erythromyalgia)
Acrocyanosis Raynauds
Raynaud Triple-colour changes: White, Blue/Gray, Red sharply demarcated In the hand, only involves fingers, never proximal to the MCP s Triggers: physical (cold), mechanical (compression, vibration), emotional stress, spontaneously ± pain, numbness, paresthesias
Benign Acrocyanosis Vasoconstriction of small arteries and arterioles or atonic dysregulation of efferent small venules Symmetric more generalized blue/purple discoloration hands/feet
Benign Acrocyanosis Episodes often longlasting Triggers less apparent, exacerbated by cold Associated with slow capillary refill and sometimes hyperhidrosis or livedo reticulairis (mottling) Other than feeling cold, typically asymptomatic
Most things in medicine are very black and white. everything in the gray zone is referred to rheumatology clinic -Anonymous
Acrocyanosis Raynauds
Raynaud A vasospastic phenomenon Described by Raynaud in 1862 Prevalence of 5-20 % the Caucasian population Children? M : F ratio = 7 : 1 Age of onset 20-60 y
Pathofysiology Dysfunction of the autonomic nervous system, resulting in sympathetic dysregulation and parasympathetic modulation impairment
Raynaud May be associated with CNS stimulants and malnutrition (anorexia, bulemia) 46 % monophasic, 32% biphasic, 22% triphasic
Raynaud Primary or idiopathic RP: without a definable cause Secondary RP: associated disease or cause
Primary/idiopathic raynaud Most common variant in children (70%) and adults (80%) Symmetrical episodes, absence of tissue necrosis, ulceration or gangrene absence of secondary causes (evaluated by history and physical examination) antinuclear antibodies (ANA)- ESR- no abnormality at nailfold capillaroscopy
Secondary raynaud Attacks: more intense, frequent, painful Asymmetric Structural macro-and microvascularchanges
Secondary raynaud Progressive vascular occlusive disease acral skin ulcerations, necrosis and gangrene
Secondary raynaud Ischaemic lesions are typically located at the digital tips or on the extensor site of the distal and proximal interphalangeal
Secondary raynaud: causes Systemic sclerosis Mixed connective tissue disease (MCTD) Systemic lupus erythematosus (SLE) Sjögren s syndrome Dermatomyositis
Secondary raynaud: causes Endocrine diseases: Hypothyroidism Pharmacological and toxic agents: Chemotherapy drugs (vinblastine, bleomycin), cyclosporine, estrogens, non-selective betablockers sympathetic mimetic agents: Methylfenidaat (Concerta, Rilatin), amphetamines, cocaine nicotine, narcotics, arsenic, exposure to polyvinylchloride or organic solvents
RP in connective tissue diseases Initial presentation Frequency Systemic sclerosis: 84% pediatric, > 95% adults SLE: 10% pediatric, 30% adults MCTD: 50% pediatric, 85% adults
Primary versus secondary RP- Adultlitterature!! Abnormal nailfold capillary pattern: best predictor of transition to secondary RP ANA + low predictive value Anti-ENA : anti-scl70, anti-certromere (for SSc), anti-sm (for SLE), anti-rnp (for MCTD), anti-la and anti-ro (for Sjögren syndrome), anti-jo (for dermatomyositis) is more predictive of secondary disease
Connective tissue disease: general Presentation: gradual with accumulation of the symptoms over weeks to months Early symptoms: non-specific
Connective tissue disease: general anorexia, muscle ache, Fatigue weight loss unexplained fever, prolonged fever loss of appetite oral ulcers Raynaud s phenomenon skin rash photosensitivity alopecia pleuropericarditis glomerulonephritis arthritis unexplained abdominal pain muscle weakness sicca symptoms
Raynaud: laboratory evaluation blood cells count, acute phase reactions: ESR, CRP TSH, FT4 muscle enzymes serum level: GOT, GPT, CK, LDH C3, C4 autoantibodies ANA anti-ds DNA extractable nuclear antigens (ENA): anti-cenp-b, anti-scl 70, anti-pm-scl rheumatoid factor RF anti-cardiolipin IgG and IgM
Nailfold capillaroscopy
Clinical and experimental rheumatology July 2016
Systematic review 1. prevalence of Raynaud s syndrome in children and young people? 2. How many children and young people with Raynaud s syndrome develop a connective tissue disease over time? 3. What are the risk factors for progression to a connective tissue disease in children with Raynaud s syndrome?
Systematic review UK, 720 children, 12-15 years: 15% of children (18% in girls; 12% in boys) 250 children and young people with Raynaud s syndrome aged 10-20 (44% aged 10-16yrs). F.u. 1-6 y 23.6% had evolved into a connective tissue disease The mean time to development of disease: 2.4 y Pavlov-Dolijanovic S. Pediatr Dermatol 2006; 23: 437-42.
Management RP General measures Maintenance of core temperature Avoidance of cold exposure and keeping extremities warm during the winter season nitroglycerine skin patches nifedipine Cessation of vasoconstrictive Rx e.g. B blockers, methylfenidate Gloves (heated) Smoking cessation
Prognosis Benigne acrocyanosis: benign, transient primary RP: benign condition, often transient in nature, 1/3 may improve or disappear with time significant impact on their quality of life secondary RP: depending on underlying disease severe attacks persistent digital ischemia