Today, we discussed the case of a Vietnamese man who presented with chronic cough, 40 pound weight loss, and joint pain, found to have cavitary lesions in his lungs with work up revealing pulmonary TB as well as tophaceous gout on urate-lowering therapy with allopurinol leading to SJS/TEN.

Clinical Pearls: 

• Cavitary lung lesions have a broad differential (see below) aside from TB.
• Risk factors for developing SJS/TEN include HIV (100x higher risk), genetics (especially Asians and South Asians), autoimmune diseases, malignancy, and high dose/rapid infusion of offending meds.  Consider genetic testing prior to starting meds associated with this allergy (allopurinol, sulfa drugs, PCNs, AEDs, etc.) in at risk populations.
• Nikolsky sign can be positive in SJS/TEN, staph scalded skin syndrome, and pemphigus vulgaris
• Time of onset is 1-3 after starting the offending drug
• SCORTEN score is useful for determining prognosis
• Early use of cyclosporine in patients with SJS/TEN has shown significant reduction in mortality.

DDx for cavitary lung lesions

• Infection
  • Pyogenic (necrotizing pneumonia, septic emboli, lung abscess)
  • Atypical (MTB, fungi)
• Autoimmune
  • GPA >> RA, sarcoid
• Malignancy
  • Liquid (lymphoma, KS, lymphomatoid granulomatosis)
  • Solid (squamous, GU>GI)
• Vascular
  • PE
• Other
  • Foreign body granulomatosis

SJS/TEN (Steven Johnson vs toxic epidermal necrolysis)

• < 10% = SJS, > 30% = TEN, in between = Overlap
• Common causes
  • Sulfa drugs
  • Abx (PCN, quinolones)
  • AEDs
  • Allopurinol
  • Infx: Mycoplasma, graft-vs-host
  • Idiopathic
• Risk factors
  • HIV (100x higher risk)
  • Genetics
    • There are a lot of them (check on uptodate for specific drugs) but a couple examples are:
      • HLA-B*58:01 (allopurinol)
        • Patients with this positive gene has higher risk for severe cutaneous hypersensitivity reaction to allopurinol including SJS and TEN. High risk Asian populations carrying this gene are Korean, Thai and Han Chinese.
      • HLA-B*15:02 is recommended before starting carbamazepine in Asians and South Asians
      • Cytochrome CYP2C19 polymorphism
  • Autoimmune disease
  • Malignancy
  • High doses and rapid infusion of medications
• Clinical Presentation
  • 1-3 weeks after offending drug
  • Fever >39
  • Influenza-like symptoms (malaise, myalgias, arthralgias) x 1-3 days
  • Conjunctival itching or burning
  • Odynophagia
  • Cutaneous findings:
    • Acute onset macules over face, trunk, may form flaccid bullae
    • Nikolsky sign:
      • Positive when shear stress on the skin i.e. rubbing results in exfoliation. Indicates a pathology at the dermal/epidermal junction.
      • Positive in
        • SJS/TEN
        • Staphylococcal scalded skin syndrome
        • Pemphigus vulgaris
    • Asboe-Hansen sign (AKA bullae spread sign)
    • Mucous membrane involvement.
      • Eyes, mouth lesions
      • Respiratory sx
• Prognosis:
  • SCORTEN score
  • Mortality with SJS is 10%, TEN 30%
• Management
  • Supportive care for skin
  • Pain control
  • IV fluids
  • Prevention of vulvovaginal sequelae
  • Ocular management
    • Evaluate for loss of surface epithelium
    • Opthalmic therapy
      • Saline rinses to remove debris
      • Artificial tears
      • Topical steroids
      • If extensive sloughing, then amniotic membrane transplantation (prokera ring)
  • Adjunctive therapies
    • Steroids: may lead to higher rates of complications
    • IVIG: conflicting data
    • Cyclosporine: one large case series from Spain and two systematic reviews have shown that cyclosporine given at 3 to 5 mg/kg may slow the progression.  Inhibits T cell activation and thus prevents the production and release by cytotoxic T cell and natural killer cells of cytokines that could propagate SJS/TEN.
      • A study on 71 patients of whom 49 were treated with cyclosporine and 22 with other therapies found mortality rates were 10% and 32% respectively.  Expected mortality based on SCORTEN for the cyclosporine group was 24% and 29% in the other group.
      • A 2018 meta-analysis on 255 patients with TEN found that treatment with cyclosporine was associated with a 70% reduction in mortality risk
    • Plasmapharesis
    • Anti-TNF

Bonus info on gout:

• Acute flare:
  • Steroids
  • NSAIDs
  • Colchicine (avoid in severe renal or hepatic impairment or with meds that inhibit CYP450 system)
• Indications for urate-lowering therapy for chronic treatment
  • Frequent or disabling gout flares
  • Clinical or radiographic signs of joint damage
  • Tophaceous deposits in soft tissues or subchondral bone
  • Gout with renal insufficiency (CrCl<60)
  • Recurrent uric acid nephrolithiasis
  • Urinary acid excretion >1100 mg/day)
• Goal uric acid is <6mg/dL
• Agents for chronic management
  • Xanthine oxidase inhibitors
    • Allopurinol, lower dose for CKD3 or higher renal disease
    • Febuxostat, very expensive, cardiovascular and hepatic side effects
  • Uricosuric drugs: ineffective if CrCl<50. Can worsen kidney injury. Avoid use if GFR <30
    • Probenecid
    • Lesinurad
  • Uricase
    • Pegloticase, fast improvement of symptoms, contraindicated in G6PD deficiency