Category Archives: Rheumatology

Systemic onset JIA

Features

  • Prolonged pyrexia (see below)
  • Intermittent characteristic rash (see below)
  • Raised CRP, ESR, ferritin (esp over 1000 – also haemophagocytic syndromes, haemochromatosis, liver disorders, malignancy)
  • Poor response to IVIG (cf Kawasakis)
  • Leucocytosis (neutrophilia, can be leukaemoid)
  • Thrombocytosis
  • Arthritis
  • Hepatosplenomegaly
  • Generalised lymphadenopathy
  • Pericarditis

Can be systemically very unwell and potentially life threatening complications may occur early in the disease course (eg pericarditis, macrophage activation syndrome or HLH, sepsis). See the Big Sick film from Netflix. Start high dose corticosteroids after careful exclusion of other diagnoses, especially infection, Kawasaki disease, and malignancy – difficult when arthritis is absent! But maybe you have to look harder…

Systemic features may predate the arthritis by several weeks and occasionally longer. Typically involves small joints of the hands and wrists, ankles, hips, knees, and cervical spine – about 30% ultimately develop severe polyarthritis.

There are no pathognomic tests or agreed diagnostic criteria for SOJIA! Classic features:

  • quotidian (=daily) evening spiking temperature, that returns to or falls below baseline by the morning.
  • Rash is faint, salmon pink maculopapular, most obvious during pyrexia. Usually not on the face so easily missed – typically on the trunk, inner thigh and axillae, especially on areas of trauma or pressure (Koebner phenomenon).

Treat with IV methylprednisolone pulses (30mg/kg over 4 hours, max 1g, once daily for 3 days) and ibuprofen (seems better than piroxicam for SOJIA!). Oral prednisolone may then be used while methotrexate is introduced.

Juvenile Idiopathic Arthritis

Seven subtypes – only diagnose when symptoms for at least 3 months:

  • Oligo (persistent or extended) – Arthritis affecting up to four joints during the first six months of disease. If subsequently more than four joints are affected the term extended oligoarthritis is used, otherwise the term persistent oligoarthritis is used. This is the most common pattern (50% of all JIA) and usually involves large joints of the lower limbs, especially knees. These children have the best prognosis but are at high risk of asymptomatic uveitis (30%, and risk highest in monoarthritis!) and therefore must be screened regularly. In aggressive disease, can develop within 3 months of presentation. Girls mostly ankles, knees or wrists, 50% will be ANA positive and particularly associated with chronic (even subclinical) uveitis. Boys tend to get sacroiliitis and are HLA B27 positive, which is associated with acute uveitis…
  • Polyarthritis (rheumatoid factor -ve) – 5+ joints affected during first 6 months. Tends not to be hips! 17% of all JIA. Severity is very variable.
  • Polyarthritis (RF +ve) – 7% of all JIA. Symmetrical polyarthritis, nodules, and Rheumatoid factor IgM +ve at least twice, 3 months apart. Typically adolescent girls of 10yrs+. Prognosis is guarded as early joint damage often occurs.
  • Systemic onset – SOJIA, 11% of all JIA. Can occur at any age, often pre-school but rarely in infancy. Males and females affected equally.
  • Enthesitis related arthritis – inflammation of tendon insertions eg sternum, around knee (at 2,6 and 10 o’clock positions), tibial tubercle, achilles/plantar, tibialis anterior, flexor digitorum insertion in foot. Often dactylitis. Asymmetric, distal lower limbs large joints commonly affected, high risk of developing ankylosing spondylitis in early adulthood – spine rarely affected early on. BASMI score consists of 5 measurements of spinal mobility. The group also includes arthritis or enthesitis with at least two of:
    • tenderness of the sacroiliac joint and/ or inflammatory spinal pain
    • HLA B27 positive (10% of normal population)
    • family history in a first or second degree relative of HLA B27 related disease (ie arthritis, IBD, Reiter’s, uveitis)
    • anterior uveitis (usually symptomatic with redness, pain and blurred vision)
    • arthritis after 8 years of age in a boy (esp large lower limb joints).
  • Psoriatic arthritis – esp umbilicus, behind ear, scalp. The arthritis is usually asymmetrical, mixed large/small joints. Often NOT psoriasis, at least initially, but includes children with arthritis and at least two of:
    • dactylitis (fat, sore fingers!)
    • pitting or onycholysis of nails
    • psoriasis in a first degree relative
  • Other arthritis – This group is for children with idiopathic arthritis that does not fit the other groups (or into more than one! eg Crohns & UC associated arthritis, features overlap). Downs syndrome children can get a resistant polyarthritis.

Presentation

Clinically, history of pain, swelling, stiffness. Pain is usually not severe, and often avoided completely by adapting movement; can occur at night, and occurs in the joint line. Degree of pain does NOT predict severity of synovitis. Swelling may be due to effusion or bony overgrowth. Stiffness not so severe as to cause gelling ie sitting still leads to freezing (cf myasthenia gravis, hypermobility). Bony overgrowth, discrepant leg length (longer with inflammation! Leads to postural scoliosis), wasting show chronicity.

Differentials:

  • Benign hypermobility – typically get pain related to exertion, short lasting although may occur at night.
  • Reactive arthritis – can last up to 3/12.
  • Rubella, chronic meningococcus
  • HSP before rash develops
  • Rheumatic fever
  • Behçets – mouth/genital ulcers, uveitis.
  • SLE (high ESR with normal CRP, low WCC/platelets, autoantibodies) or dermatomyositis (stiffness, rather than true arthritis – proximal muscle weakness, high CK)

Investigations:

  • Mono JIA usually CRP <7 – else beware infection
  • Micro of joint fluid nonspecific
  • XR – to exclude tumour etc. Lucency in metaphysis may be marrow infiltration in leukaemia, Brodie’s abscess or Langerhans’ histiocytosis. Moth eaten appearance and onion skin periosteal reaction suggests tumour or infection.
  • RF v non specific, like autoantibodies, only significant in discriminating teenage girls with adult type Rheumatoid Arthritis.
  • US is good but operator dependent. MRI probably better, predicts extension in mono, 4-11/12 before clinical signs.

Treatment

NSAIDs and intra-articular steroids work quickly. Ibuprofen can be given at high dose (10mg/kg qds), else Diclofenac 3-5mg/kg in 3-4 divided doses, max 150mg. Piroxicam is once daily, which is convenient but it probably has more GI/cutaneous side effects. No longer considered appropriate for acute pain.

Routine NSAIDs are probably pointless; if you need regular anti-inflammatories, you should probably be on a disease modifying agent eg methotrexate.

Joint injections are given under general anaesthetic in young children or with entonox in older children. Lederspan (triamcinolone) 1mg/kg max 40mg used for big joint, 0.5mg/kg for wrist, TMJ. Knuckles will only take 0.1-0.2ml before they start to leak (which leads to subcut atrophy). Injecting multiple (eg >6) sites can result in Cushings for 3-6/12. Better to pulse methylpred? (Kennilog is another formulation, but seems to give more Cushings). Most patients tolerate injections well and have no loss of function immediately after; physio is usually started after 24hr. How often? Balance of steroid effects and uncontrolled joint disease…

Methotrexate Side effects: GI (nause, ulceration, diarrhoea), hepatotoxicity (reversible elevations of serum liver enzymes eg 3x upper limit normal common), Pulmonary (oedema, pleuritic pain, pulmonary fibrosis, interstitial pneumonitis), mood changes, Renal (haematuria, dysuria, renal failure) – plus usual chemo stuff ie bone marrow suppression.

BNFc

Methotrexate is the disease modifying drug of choice – early use helps to reduce joint damage and minimise the exposure to, and side effects of, corticosteroids. Well tolerated in most children but often causes nausea the day after administration (so usually given on Friday to avoid affecting school). Avoid alcohol, as potentiates risk of cirrhosis. Takes 6-8 weeks to become effective so cover interval with intravenous methylprednisolone. The theoretical risk of malignancy and infertility has not so far been borne out in long term outcome studies. Folic acid improves tolerability but not clear what regimen to use – BNF suggests 5mg once weekly or 1mg daily, theoretically it should not be given within 24 hours of the MTX [so once weekly sounds easier]. Methotrexate is given once a week at 10-25mg/m2 – can be oral but subcut route improves bioavailability at doses beyond 10mg/m2. Metojet has better shelf life (10 months). Regular blood tests to monitor inflammatory markers and side effects eg monthly for 6 months then 3 monthly thereafter. Not great for axial disease ie HLA B27.

Steroids are useful for treating acute flares. Methylprednisolone can be given once daily for 3/7 to control severe exacerbations, then once weekly thereafter (30mg/kg, max 1g). Don’t work well for axial disease though ie HLA B27 (although may be good for peripheral joints) – TNF blockade (ie etanercept or infliximab) effective.

Patients who are refractory to high dose parenteral methotrexate are considered for monoclonal antibodies such as Etanercept/infliximab (TNF antibody), autologous stem cell transplantation, or very high dose immunosuppression.

  • Etanercept (Embrel) used to be twice weekly subcut injection but most now do once weekly 0.8mg/kg. £10 000pa.
  • Infliximab is an infusion, given at 0, 2, 6 weeks then 8 weekly thereafter. Children usually start at 5mg/kg. If control not achieved, a higher dose could be used else the interval reduced. Patients should get a CXR and Mantoux before starting in view of the particular risk of mycobacterial disease.
  • IV immunoglobulin has been used eg 2 doses on consecutive days monthly. Very expensive.
  • Mycophenolate – related to azathioprine. Used for connective tissue disease. SE gastrointestinal, liver, bone marrow. 600mg/m2 BD

Calcium and vitamin D supplements are often given for bone health.

Patients on immunosuppressants should avoid live vaccines and beware of infection. If unwell enough to need antibiotics they should probably stop treatment temporarily. Varicella is a particular concern – if contact with chickenpox and non-immune, consider VZIG or oral aciclovir for prophylaxis, and early IV aciclovir treatment. See Greenbook.

Not clear when to wean… Many patients do well for a year or so before their condition begins to worsen, swapping to another agent often works, and swapping back is also a useful option.

Outcome

JIA is a not a benign disease and outcome is variable. At least a third of patients have ongoing active disease into adulthood and many have sequelae eg:

  • joint damage requiring joint replacement
  • short stature from chronic disease compounded by steroid toxicity
  • localised growth problems (micrognathia or leg length inequality)
  • visual loss from uveitis
  • osteoporosis: one off DEXA scan not predictive of # (maybe better if serial scans?) so clinical. Minimize steroids; optimize exercise, nutrition, growth/puberty, calc/vitD/bisphosph

Bisphosphonates seem to be effective for increasing bone mass in JIA. Flu-like symptoms with first IV dose can be treated with paracetamol and tend not to recur.

Uveitis

The Uvea is the term for the whole eye (uvea=peeled grape). Whereas conjunctivitis looks like a red eye, it’s only really the surface that is inflamed. With uveitis, all the different tissues of the eye are inflamed. Acutely, might not look that different to conjunctivitis but painful, whereas latter usually just itchy. Anterior chamber starts to fill up with inflammatory cells so vision starts to deteriorate. An irregular pupil due to synechiae can eventually be seen, with hypopyon. Cataracts and scarring can follow.

Chronic on the other hand can be subclinical but potential for visual loss so screening important in associated conditions.

Usually idiopathic, otherwise:

  • Juvenile idiopathic arthritis – about 10% of patients with non-oligoarthritis, and 30% of ANA positive oligo so pretty common
  • HLA-B27 – with or without other B27 conditions such as Ankylosing spondylitis
  • Behcet’s disease (so do HLA B51)
  • Crohns disease and other IBD
  • Granulomatosis with polyangitis (ex-Wegeners)
  • Sarcoidosis (so do chitotriosidase)
  • Tubulointerstitial nephritis and uveitis (TINU) syndrome

Some infections can cause it:

Rheumatic fever

Rare in developed world now, still common in underdeveloped world, or at least in underdeveloped communities eg Aboriginal Australians.  Prob also genetic susceptibility.

Caused by Group A streptococcus.  Important cause of acquired heart valve disease.  Can recur.

Probably cross reactivity between specific Group A strep M proteins and human tissues.

Diagnosis

Jones criteria:

  • Major
    • Carditis eg new murmur.  Mitral most commonly, classically apical blowing pan-systolic.  Aortic next most common.
    • Arthritis esp large joints.  Migratory.
    • Subcutaneous nodules – these are the most uncommon major criterium.  Typically over extensor surfaces of joints, 0.5-2cm, symmetrical.
    • Sydenhams chorea
    • Erythema marginatum – not specific to rheumatic fever.  Serpiginous or annual eruption, can look similar to erythema multiforme. Provoked by warmth eg bath.  Non pruritic.
  • Minor
    • Fever
    • Arthralgia
    • Prolonged PR interval on ECG
    • Elevated CRP/ESR
  • 2 major or 1 major plus 2 minor, plus confirmation of group A streptococcal infection eg positive culture, high ASO titre sufficient for diagnosis.

Note that initial infection may be subclinical eg pharyngitis, erysipelas. Symptoms of rheumatic fever develop 10 days to several weeks later. Chorea can appear months later.  Low threshold for echo as carditis can also be subclinical.

UFMG rating scale for assessing function.

Treatment

Antibiotics – Treat with penicillin,  this does not however affect clinical course but hopefully prevents further spread of that particular bug. Traditionally single dose intramuscular Penicillin G Benzathine.

NSAIDs for joint pain.  Usually dramatic response, if not then reconsider diagnosis!

Valproate for chorea, possibly steroids – see Sydenham’s.

Aspirin and/or Steroids for carditis, but not much evidence.  Diuretics, ACE inhibitors for cardiac failure.

Long term treatment

Recurrence with progression of valve damage is the main concern, and well recognized.  Regular intramuscular penicillin (benzathine pencillin G) every 2-3 weeks has the lowest recurrence rates but oral penicillin V more acceptable.  Erythromycin or cephalexin if allergic.

WHO recommendations:

  • Rheumatic fever without carditis: 5 years after last attack or until age 18 (whichever is longer)
  • Rheumatic fever with carditis but without residual disease: 10 years after last attack or until age 25 (whichever is longer)
  • Residual valve disease or valve replacement: lifelong

American heart association guidelines vary slightly.

Henoch Schonlein Purpura

or HSP. Usually preschool but any age! Boys more than girls. Vasculitis.

Features:

  • Urticarial rash becoming purpuric but still raised (pathognomic), extensor surfaces of lower limbs incl buttocks, sometimes trunk, rarely face (infant).  Accompanying soft tissue swelling, as seen in photo in feet.
  • Arthralgia (not migratory, cf acute rheumatic fever)
  • Abdo pain, often severe requiring laparotomy, possible intussusception, Melaena
  • Glomerulonephritis, usually asymptomatic cf streptococcal, but a few develop diffuse proliferative lesions with irreversible renal damage.
  • Scrotal rash/bruising common, rarely torsion
  • Rarely encephalitis, seizures

Pathology

Leukocytoclastic vasculitis with glomerular mesangial IgA deposits.  Biopsy of patients with IgA nephropathy identical, and indeed both groups have defective IgA1 glycosylation, which may explain why they may aggregate and precipitate IgA in small vessel walls as well as in the glomerular mesangium.

Complications

Complications and relapse associated with age esp over 6yr. 50% relapse, usually within 6 weeks but can be up to a year later; 50% of those will relapse more than once. Treat with NSAIDs for joint pain, strong analgesics for abdo pain. Small study from Turkey found that Ranitidine reduced symptoms.

Reviewing 101 children with abdo involvement those who did not receive steroids had an average of 5 days of abdominal pain, whereas all those treated recovered within 24 to 48 hours of starting steroids (letter, J Pediatr Gastroenterol Nutr. 31(3):323-4, 2000).

Abdominal pain is a predictor of renal involvement, so maybe that’s the best reason for giving steroids… (Kidney Int 1998; 53:1755-9).

Renal disease

20 to 90% risk of renal disease, but generally mild (mostly just mild proteinuria and/or haematuria)! Normal urinalysis at day 7 has 97% negative predictive value for chronic renal disease [PLoS One 2012;7:e29512].

About 56% of those children with renal disease develop signs and symptoms of renal disease a week or more after presentation, although generally in first month.  Can be up to 6 months later.  Incidence of renal failure in HSP nephritis is just 2 to 5%.  Risk factors are severe abdominal pain (OR=2.1), age >8yrs (OR=2.7), and relapsed HSP (OR=3).[Arch Dis Child. 2010 Nov;95(11):877-82. doi: 10.1136/adc.2009.182394]

A normal urinalysisNB Children who appear to recover may have significant renal disease many years later. (Lancet. 339:280282, 1992).

If more than 50% crescents on biopsy, then poor prognosis.  Only 1% get that far.

Archimedes in 2012 found 3 RCTs of steroids, treatment courses 2-4 weeks, seemed to shorten duration of abdominal pain, with most obvious effect when used early.

Dudley trial of early steroids (day 7) failed to find any benefit at 12 months (n=352).  Quite a high proportion of drop outs unfortunately, but prob not enough to influence results.  Doesn’t answer question of what to do if severe disease at onset eg nephrotic range.  [Arch Dis Child. 2013 Oct;98(10):756-63.]

Non-randomized prospective clinical trial of 223 kids showed that steroids were effective in reducing the severity of abdominal and joint pain and in treating renal disease – steroids did not prevent the development of nephritis [Archives of disease in childhood. 2010;95:877–82, doi: 10.1136/adc.2009.182394 ].  Previous systematic review suggested that steroid treatment at diagnosis did not reduce the median time to resolution of abdominal pain but did significantly reduce the mean resolution time, and increased the odds of resolution within 24 hours.

There is no proven benefit of corticosteroids in the treatment of established HSP nephritis (2009 Zaffanello systematic review, evidence is poor), but used anyway.

The major risks of corticosteroid treatment in children with HSP are masking an acute abdomen or intussuception, and GI bleeding.

Follow up

Scottish guideline (based on Alder Hey pathway) – for routine presentation, do 1 week, 1 month, 3/6/9/12 month BP and urinalysis check. No need for parents to check at home otherwise.  Continue 6 monthly until 2 consecutive urines normal.

If hypertensive or urinalysis pos, then do proper urine protein:creatinine ratio, U&Es, MC&S. Isolated haematuria is benign. As soon as urinalysis becomes normal, child can have routine follow up. Persisting proteinuria of + or more needs more frequent follow up eg 2 weekly, 2 monthly then 3 monthly with the second line investigations. Refer urgently for confirmed hypertension, nephrotic range proteinuria (P:CR over 200mg/mmol), or GFR under 60 ml/min/1.73m2. Refer for assessment if GFR 60-80, proteinuria 50-200 mg/mmol, or persistent macroscopic haematuria at 2 months, or persistent haematuria/proteinuria at 1 year.

A systematic review found no risk of long-term renal impairment in children with Henoch-Schonlein purpura with normal or minimal urinary findings without nephritic or nephrotic syndrome or renal failure (Arch Dis Child 2005;90:916-20). If urine analysis is normal at presentation, then test for 6 months after the last symptoms. If there is renal disease at presentation, then the risk for progression seems to be more associated with rising proteinuria during follow-up rather than presentation features. (Am J Kidney Dis 2006;47:993-1003)

Chronic fatigue syndrome

US IOM expert panel have rejected this name, as patients hate it!  Myalgic encephalitis (ME) also rejected on basis of insufficient evidence that this is the pathological process.  They suggest “Systemic exertion intolerance”, which is probably even more rubbish, in my opinion.

Diagnostic criteria: all of the following 3 [BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h775]

  1. Substantial reduction/impairment in pre-illness levels of activity, that persists for more than six months [NICE 2007 says 3/12 for children], and accompanied by fatigue (often profound, new or definite onset, not the result of ongoing excessive exertion and not substantially alleviated by rest)

  2. Worsening of symptoms after any type of exertion (including cognitive and emotional stress) – “post-exertional malaise

  3. Unrefreshing sleep, and/or sleep disturbance.

In addition, should have at least one of:

  • Cognitive impairment
  • Orthostatic intolerance.

Doesn’t mention chronic pain?! NICE says reconsider diagnosis in absence of cognitive difficulties or chronic pain.

Causes

Evidence (reproducible) implicating certain infections as a trigger. Co-existing mood disorder in substantial proportion of patients, sometimes sleep-wake disorder – likely to perpetuate/exacerbate.

Brain imaging has identified alternations suggesting that it is a brain problem.

Investigations

[NICE 2007]

  • Urinalysis
  • FBC, LFTs
  • TFTs
  • Coeliac disease screening
  • CK
  • ESR/CRP
  • Glucose
  • Ferritin

NOT microbiology unless indicated: borrelia, HIV, Hepatitis viruses, EBV, CMV, toxoplasmosis

Management

Recent Cochrane review of graded exercise therapy – may benefit sleep, physical function, self-perceived general health, and no evidence that it worsens outcomes. Curiously, no evidence for loss of aerobic fitness! Perhaps graded exercise tackles a hyper-reactive CNS response to exercise-related physiological signals. Note that fear of physical activity becomes conditioned when it commonly exacerbates symptoms.

Relaxation techniques recommended by NICE.  CBT also effective. Analysis of both CBT and graded exercise suggests that benefit comes from reducing inactivity.

Sleep hygiene important.  Avoid day time naps, especially since sleep doesn’t usually help anyway!

Many people find exclusion diets useful, esp bowel symptoms, not recommended but involve dietician if attempted anyway.

Equipment to maintain independence can improve quality of life and should be part of overall management.

Beware boom-bust! Many patients over do it when they have a period of relative wellness.

But are these cures? PACE trial aimed for less than full restoration of health as “recovery”, future trials should use clinically relevant improvement and patient self-perception.

Prognosis

Important to be honest at time of diagnosis.  More optimistic in young people.  Most adults improve, some are able to return to usual activities but others experience long term symptoms or relapse.

[bmj 2015;350:h2087][NICE 2007

Lyme Disease

Borrelia (spirochaete) infection, spread by ticks (Ixodes), common in localized areas of Europe and North America (forest environments).

Differential includes possible co-infection from other tick born organisms viz anaplasmosis, or babesiosis.

Vaccine available if likely to be at risk.

Clinical

Skin – Erythema migrans is the classic skin lesion, a spreading ring usually at the site of the bite but can be multiple and at different sites.  Develops over a week or two, up to 40 days, can last months.  Looks like erythema multiforme, but time scale different.  Any insect bite hypersensitivity will look similar.  Lyme lymphocytoma is a painless bluish red nodule or plaque, especially on the ear but also reported on the nipple and scrotum.  More common in children.  May persist for months, can precede other features.  Acrodermatitis chronica atrophicans (ACA) is almost exclusively seen in adults, predominantly women, and is an eruption with chronic, progressive red or bluish-red lesions, usually on the extensor surfaces, with later atrophic, fibroid or sclerodermic changes.

Arthritis – uncommon, presents as recurrent inflammation of 1 or more large joints, usually the knee. Swelling can be disproportionate to pain.  Can become more persistent – in a minority, despite treatment, inflammation becomes chronic (presumably immune-mediated).

Carditis occurs rarely, and almost always with other clinical features.  Usually partial heart block, but can be complete, usually resolves within a week.

Neurological – isolated facial palsy, meningitis, other cranial nerve palsies, meningoencophalitis, polyradiculopathy.  There is a small proportion of children who can present with non-specific headache, fatigue, neck pain without clear neurological signs (and also the rare case of raised intracranial pressure).

Other rare disease manifestations include uveitis, iridocyclitis and keratitis.

Diagnosis

For erythema migrans, clinical diagnosis is adequate, and antibodies only positive in 30-70% anyway!  If atypical, do acute and convalescent serology.  Current tests have reasonable  sensitivity and specificity, if done acutely with high probability cases.  However, false negatives possible in early disease, especially in EM and early neurological.  Early antibiotic treatment is also believed to potentially block antibody production.

For early neuroborreliosis, antibodies 80% sensitive, rises to virtually 100% for late or ACA.

Antibodies can then persist for months or even years after successful treatment of the infection, so repeat testing is not useful for monitoring treatment success.

First line ELISA test can have false positives for other spirochaetes, glandular fever and autoimmune conditions.

Western blot for IgM is done as a second line test for ambivalent cases to increase specificity, but cut offs for both serology and Western blot can be an issue though, with potential false positives for other acute infections and autoimmune conditions.  Definitely needs to be an approved lab . [European Union Concerted Action on Lyme Borreliosis (EUCALB) initiative criteria, Clin Microbiol Infect 2011; 17: 69–79, DOI: 10.1111/j.1469-0691.2010.03175.x]

The idea that there are seronegative “chronic Lyme” cases has little evidence to support it, with only 2 possible cases reported (ACA and arthritis, not neuro).

Consider PCR on skin biopsy, synovial fluid/tissue. Not great for CSF.  Culture is difficult.  CSF antibodies for neuroborreliosis; consider for isolated facial palsy.

Treatment

The most commonly recommended first-line treatments for different stages of Lyme borreliosis in Europe are:

  • Erythema migrans/borrelial lymphocytoma:  10-14 days Doxycycline if 9yr+ (initially 5 mg/kg in 2 divided doses on day 1, then 2.5 mg/kg daily in 1–2 divided doses, max dose 200mg, for a total of 21 days, option for higher dosing) – 10 days courses of doxy effective in US trials.  Else Amoxicillin 50mg/kg/d, max 500mg TDS (10-14 days)[BNFc says 30mg/kg/d, max 1g, TDS for 21 days].  Don’t delay treatment pending test results.  Scandinavia use 10 days Pen V (100mg/kg/d, max 1000mg TDS). BNFc says Azithromycin as alternative.
  • Isolated facial palsy: 14 days Oral doxycycline  – else as above.  Doesn’t probably help resolution but may prevent later complications.
  • Meningitis/radiculopathy: PO Doxycycline or IV Ceftriaxone  50-100mg/kg/d, max 2g daily (14-21 days). [BNFc talks about CNS disease separate from cranial/peripheral nerves]
  • Encephalitis, myelitis: Ceftriaxone (14 days)
  • Lyme arthritis: Doxycycline (28 days) else Amoxicllin (21-28 days)
  • Carditis: Ceftriaxone during pacing, else PO doxycycline (14 days)
[position statement by the British Infection Association, J Inf 2011;62:329]

Ceftriaxone is the most commonly preferred parenteral agent, with once-daily dosing facilitating outpatient treatment. Recent prospective studies have shown that oral doxycycline is noninferior to ceftriaxone in neuroborreliosis, and it is now recommended in Europe for the treatment of acute facial palsy (FP), meningitis and radiculoneuritis. Ceftriaxone currently remains the preferred choice for children with other presentations of neuroborreliosis and for those with contraindications to doxycycline.

Several recent EM treatment studies have incorporated noninfected control groups. Excellent responses were seen, with resolution of rash within 7–14 days. Nonspecific symptoms including headache, myalgia, arthralgia, fatigue and parasthesias were no more common in cases than controls at 6-month follow up.

 Pediatric Infectious Disease Journal Volume 33(4), April 2014, p 407–409.  DOI: 10.1097/INF.0000000000000248. 

Ehlers-Danlos syndrome

Covers a spectrum of problems, classified by Beighton (as in hypermobility, Marfans etc).

  • Type 1 is severe, commonly born prematurely due to premature rupture of membranes, joint and skin laxity are gross with frequent orthopaedic problems. History of hernia repair? Aortic root dilatation and mitral valve prolapse have been reported but evidence on prognosis is still conflicting.
  • Type 2 is milder and so often underdiagnosed.
  • Type 3 is benign joint hypermobility without skin problems!
  • Type 4 is the rare but severe form where risk of arterial rupture, mostly between ages 20-40. Autosomal dominant so may be history, sometimes characteristic facies. Abnormal bruising is characteristic and the skin is unusually translucent but paradoxically it is not especially hyperextensible, and hypermobility may not be very obvious (perhaps only in fingers)! Problems rarely present before age 20 so important to pick up. Arterial rupture can affect anywhere – aneurysm or bizarre fistula may precede, else trauma or surgery may be a trigger. Bowel rupture is often seen although not usually lethal, pregnancies can be affected by uterine rupture +/- haemorrhage.

Sheffield does genetic testing.

Haemophagocytic syndromes

A group of disorders, including haemophagocytic lymphohistiocytosis and Macrophage activation syndrome, characterized by :