Panniculitis

Question 1

Classification

Answer 1

PREDOMINANTLY SEPTAL
Erythema nodosum
Superficial migratory thrombophlebitis 
Cutaneous polyarteritis nodosa
Necrobiosis lipoidica
Deep morphoea
Subcutaneous granuloma annulare
Rheumatoid module
Necrobiotic xanthogranuloma

PREDOMINANTLY LOBULAR

Question 2

Erythema nodosum (EN)

Answer 2

Most common panniculitis
Reactive process
May be triggered by variety of causes

CLINICAL FEATURES
Young adults

Sudden eruption 
Several erythematous 
Tender, warm
Non-ulcerating
Nodules, plaques
Shins, ankles, knees
Different stages of evolution

Symmetrical, bilateral distribution
May become confluent

Occasional extension to other sites -

• Thighs
• Extensor arms
• Neck
• Face

Early lesions —> Bright red colour, slightly raised
After few days —> livid red/purplish colour, become flat
Later stage —> yellow/greenish colour (like a deep bruise)

Resolves spontaneously within 3-6 weeks Without -

• Residual marks
• Ulceration
• Scarring
• Atrophy

Common Assoc constitutional symptoms -

• Fever 38-39 degree celsius (less common in kids)
• Fatigue, malaise
• Headaches
• Arthralgias (less common in kids)
• Abdo pain
• D&V
• Cough
• Conjunctivitis

Rare clinical manifestations -

• LN
• HSM
• Pleuritis

Recurrent episodes common esp. in idiopathic EN and EN assoc with strep URTI

Can be IDIOPATHIC with no underlying cause found

ASSOCIATED DISEASES
Concomitant presentation of Sweet syndrome and EN as ractive processes —> assoc with strep throat infection, sarcodosis, Crohn disease, AML

TRIGGERS
Bacterial infections*** (most common)
- TB —> can have bilateral hilar LN + EN
- Leprosy
- Atypical mycobacteria infections
- Strep infections —> EN develops 2-3 weeks after —> raised ASOT (throat swab may be neg when lesions appear) —> can have bilateral hilar LN + EN
- Mycoplasma pneumoniae infections
- Brucellosis
- Chlamydia psittaci infections
- Q fever
- Rickettsiae
- Salmonella infections
- Shigella infections
- Yersinia infections

Viral infections

• Hep B
• Hep C
• EBV/infectious mononucleosis
• CMV
• HIV
• Measles
• Varicella
• Parvovirus B19
• HSV
• Orf

Fungal infections

• Aspergillosis
• Blastomycosis
• Coccidioidomycosis —> can have bilateral hilar LN + EN
• Histoplasmosis —> can have bilateral hilar LN + EN
• Sporotrichosis

Prozoal infections

• Giardiasis
• Ascariasis
• Toxoplasmosis
• Hookworm infestation

Inflammatory disorders (common)

• Sarcoidosis*** (most common) —> mindful bilateral hilar LN + EN do not occurs exclusively in sarcoidosis
• Inflammatory bowel disease i.e. Crohn disease > Ulcerative colitis*** (most common) —> EN may precede the bowel disease
• Coeliac disease
• Ankylosing spondylitis
• Relapsing polychondritis
• Reactive arthritis
• Sjogren syndrome
• Lupus erythematosus
• Granulomatosis with polyangiitis (Wegenera granulomatosis)
• Acne fulminans
• Sweet syndrome, Behcet disease

Other disorders -
- Pregnancy***

Meds - Analgesics

• Acetaminophen
• Ibuprofen, naproxen

Meds - ABs

• Amoxicillin
• Dicloxacillin
• Cotrimoxazole
• Sulfonamides***
• Levofloxacin

Meds - Acne drugs

• Minocycline
• Isotretinoin

Meds - Hormones

• OCP*** Iesp ones with high oestrogen content)
• progestin

Meds - Antiepileptics

• Phenytoin
• Carbamazepine

Meds - Other

• Bromides***
• Frusemide
• G-CSF
• Infliximab
• Sulfasalazine

Malignancy (less common)

• Visceral malignancies i.e. colon, liver, lung, renal, uterine
• Haem malignancies i.e. non-Hodgkin lymphoma, MDS —> can have bilateral hilar LN + EN

CLINICAL VARIANTS
Unilateral erythematous nodules involving palms or soles that appear after physical activity in children

DDX
Behcet disease —> Bx differentiates

PATHOGENESIS
? immune complex deposition in and around the veins of the connective tissue septa of the subcutis
? Type 4 delayed hypersensitivity reaction

IX
History - 
Previous diseases 
Meds 
Foreign travel (atypical infections)
Pets (zoonophilic infections)
Hobbies (source of infection)
Familial cases (if the cause is contagious)

Confirm Dx -
Skin biopsy —> predominantly septal panniculitis without vasculitis
- Septa in the subcutis thickened and oedematous, infiltrated by inflammatory cells
Composition of inflammatory cells varies with stage
- Early lesions —> septa contains neuts interstitially arranged between collagen bundles +/- eos, sometimes extensiom of the infiltrate to the periphery of the fat lobule surrounding individual adipocytes in a lace-like fashion but wothout necrosis of the adipocytes at the centre of the fat lobule —> not a true lobular panniculitis
- Present in all stages of EN —> Miescher radial granulomas = histo hallmark (small well-defined histiocytes sround a cemtral stellate/banna shaped cleft)
- Late lesions —> septal fibrosis, periseptal granulation tissue partially replacing fat lobules, infiltrate contains lymphocytes, histiocytes, multinucleated giant cells
- Overlying dermis - superficial and deep perivascular inflammatory infiltrate predominantly composed of lymphocytes
- No true vasculitis (but rare cases with necrotising small vessel vasculitis with fibrinoid necrosis of the small bessels within the septa)

Initial panel for associations - 
FBC
ESR
ASOT (strep infection)
Throat swab MCS (strep infection)
Urine MCS (infection)
Qgold (TB)
CXR (TB, malignancy)

When aetiology unclear -
Test for Bacterial/viral/fungal/protozoal infections most prevalent in the area

GENERAL MX
Imdemtify and mx underlying cause esp if infectious aetiology
Limit physical activity/exercise
Bed rest

SYSTEMICS (acute cases)
Oral NSAIDS (analgesia, hastens resolution) —>
- aspirin 300mg daily
- indomethacin 100mg - 150mg daily (25mg - 50mg TDS)
- Naproxen 500mg daily
- C/I in IBD

SYSTEMICS (persistent cases)
Oral KI (potassium iodide) —> anti-neutrophilic
- 300mg - 900mg daily i.e. titrate from 100mg TDS —> 300mg TDS
- a saturated solution 1g/ml —> max 0.3mls (300mg) TDS in water or orange juice (tastes foul)
- Check baseline TFTs, thyroid ABs
- Monthly TFT
- S/E severe hypothyroidism d/t exogenous intake of iodide
- C/I during pregnancy —> may induce goitre in the foetus

Oral prednisolone (not isually indicated for EN)

• Should not be commenced unless infectious aetiology i.e. TB/malignancy excluded
• 25mg - 40mg daily for 5 days —> resolution of nodules in a few days

Oral Colchicine 0.5mg daily to TDS esp in setting of Behcet’s disease —> anti-neutrophilic

Oral HCQ 200mg BD

Thalidomide

Anti-TNF (EN responded in patients with IBD treated with these agents)
S/C Etanercept —> can cause EN
S/C Adalimumab
IV infliximab —> cam cause EN

INTRALESIONAL RX (solitary persistent lesions)
ILCS with triamcinolone acetonide 10mg/ml (Kenacort A10)
- Inject into centre of nodules

COMPLICATIONS —> uncommon
Retrobulbar optic nerve neuritis during acute EN
Coexistence of EN with Erythema multiforme Lichen planus d/t reactivation of Hep C

COURSE/PROGNOSIS
Acute onset
Self-limited course
Mostly regress spontaneously in 3-6 weeks
Relapses common esp. in idiopathic EN and EN assoc with strep URTI