Leg ulcer D/Ds

1. A CASE OF RECURRENT LEG ULCERS Dr Rohit K. Singh 2 nd yr Resident (MD Derm , Ven , Leprosy) Base Hospital, Lucknow

2. Case Chandra Bhan Singh, 31 yrs old male, serving soldier from Etah (U.P) DOA - 31 St Dec 13 Presenting complaint - Recurrent ulcers over anterior aspect of right leg × 16 months

3. History of present illness Onset –insidious and progressive Started as itching over anterior aspect of right leg In a week time patient developed a small ulcer over the same area Ulcer grew rapidly in size and it was associated with intense pain and pus discharge Ulcer healed gradually in about 8 to 10 weeks duration with scar formation, patient also took some oral and topical medications for this.

4. History of present illness Similar ulcers continued to occur on the right leg and subsequently healed with scarring. Presently patient has developed similar ulcer over anterior aspect of right leg, 6 weeks back.

5. History of present illness No h/o Oral or topical drugs preceding the ulceration, fever, joint pain, trauma Cough with sputum discharge, photosensitivity Recurrent oral ulcers, prolonged standing, pain in legs Symptoms of immunosupression , unprotected sexual contact or promiscuous behavior Irregular bowel movement, blood in stool Psychiatric illness

6. History contd.. Past history No h/o hypertension, diabetes mellitus, tuberculosis Treatment history Oral amoxy-clav Oral Rifampicin NSAIDS Topical antibiotic creams Family history – no h/o similar disease in the family Personal history Married for 9 years with 2 children No h/o of alcohol intake Non smoker Non tobacco chewer

7. General Examination BMI – 24 kg/ msq Pulse - 76 / min, regular BP - 120/ 86 mm Hg, T - 98 º F RR - 16 / min No pallor, icterus , cyanosis, clubbing or lymphadenopathy Pedal oedema absent Peripheral pulses ( dorsalis pedis ) on both sides are normally palpable

8. Dermatological Examination

9. Dermatological examination Oral mucosa Genital mucosa NAD Nail Hair

10. Systemic Examination Resp - NAD CVS – S1, S2 normal CNS – NAD Abdomen - No organomegaly

11. Provisional diagnosis Clinical impression – Pyoderma gangrenosum D/D Cutaneous tuberculosis Vasculitis induced ulcerations

12. Investigations Hb – 13.9 gm% TLC – 6900/ cumm DLC- N 66%, L 25%, M 03%, E 03% ESR – 18 mm fall in 1 st hr Platelet count – 1.8 lacs LFT – Serum bilirubin - 0.6 mg/dl - SGOT – 21 U/l - SGPT- 36 U/l Renal functions- -Blood urea- 34mg/dl -Serum Creatinine - 0.8 mg/dl Blood sugar F – 95 mg/dl PP – 110 mg /dl Urine RE – NAD Pus culture and sensitivity – no growth after 48 hrs of incubation

13. Investigations PBS - NAD HBsAg – negative Anti HCV Ab – negative ANA – negative Rheumatoid factor - negative VDRL – non reactor Pathergy test - negative Doppler study of limbs – NAD USG abdomen – normal scan Chest X ray - NAD G6PD – non reactor

14. Investigations Colonoscopy – NAD Skin Biopsy – Pyoderma gangrenosum Biopsy number – B/27/14 , CH ( CC), LKO. Epidermis – mild acanthosis Dermis - dense neutrophilic inflammatory cell infiltrate and fibrinous exudate with mild perivascular infiltrate Tubercular / atypical mycobacterial granulomas not seen

15. Histopathological report 5X 10X

16. Histopathological report 40X

17. Final diagnosis Rapid progression of the lesion with pain out of proportion to the size of ulcer Exclusion of other causes of ulcer Presence of cribriform scarring Appropriate histological findings Final diagnosis Pyoderma gangrenosum

18. Management : Before biopsy report Topical management Saline irrigation 2% mupirocin ointment dressing daily

19. Management : Before biopsy report Systemic treatment Initially 5 days of amoxy-clav 1 gm BD Cap. Multivitamin B/C once daily

20. Management : After biopsy report Topical management Saline irrigation 2% mupirocin ointment dressing daily Systemic treatment ( wef – 23 rd Jan 14) 4 wks of oral prednisolone starting with 50 mg OD and tapering by 10mg every week. Simultaneously starting oral Dapsone 100 mg daily.

21. Post – Treatment Before biopsy report Before treatment 2 weeks after treatment Patient only on topical 2% mupirocin oint .

22. Post – Treatment After biopsy report

23. 1 week after treatment 2 weeks 3 weeks 4 weeks

24. 28 th Feb 14 5 th week

25. DISCUSSION

26. What are the common causes of leg ulcers?

27. Causes of leg ulcers Vascular Venous Arterial Mixed Neuropathic Leprosy Tabes dorsalis Syringomyelia Metabolic Diabetes Gout Porphyria Haematological Sickle cell disease Cryoglobulinemia

28. Trauma Pressure Injury Burns Tumors Basal cell carcinoma Squamous cell carcinoma Infection Bacterial Fungal Protozoal Panniculitis Necrobiosis lipoidica Fat necrosis Pyoderma Gangrenosum Psychiatric Dermatitis artifecta

29. Pyoderma gangrenosum Def : a rare, non – infectious neutrophilic dermatosis commonly associated with underlying systemic disease. Cutaneous manifestation of systemic disease Brocq first described PG in 1916 Later described by Brunsting et al in 1930 Females > males B/w 40 and 60 years

30. Aetiology and pathogenesis Immune – mediated process ( i ) Humoral defects Autoantibodies againt skin and bowel Arthrus / Schwartzmann reactions Cross-reactivity b/w bacterial and cut. antigens with E.coli IL-8

31. (ii) Cell – mediated defects Cutaneous anergy to candida , streptokinase, PPD Altered production of macrophage inhibition factor by lymphocytes Association b/t IBD and arthritides Clonal restriction of T- cells and neutrophils Vasculitis C-ANCA OR P-ANCA Drug associated like thiouracils Smoking Familial associations PAPA( pyogenic arthritis, PG, acne)

32. Clinical manifestations PROGRESS Deep painful subcutaneous nodule/pustule formation Ulcer formation (may be > 30cm) Defined violaceous borders U ndermined edges Granulation tissue S urrounding zone of erythema P urulent exudate Classical /ulcerative variant

33. Other features Solitary or multiples Heals with atrophic cribriform scarring Most commonly at legs (extensor aspect) Other sites Upper limbs Face Trunk Mucosal(oral & genital) Sites of cutaneous trauma( pathergy phenomenon) Site of surgery

34. Clinical manifestations Systemic features Fever Myalgia Malaise A rthralgia Frequent disease associations Inflammatory bowel disease(IBD) Arthritis Monoclonal gammopathy Internal malignancy Over 70 % have one of these

35. Disease associations Category Examples Gastrointestinal Ulcerative colitis, Crohn’s disease , Intestinal polyps, Gastroduodenal ulcers Arthritides Rheumatoid arthritis , Seronegative arthritis, Osteoarthritis Haematological Leukemias , Myelodysplastic syndromes, Myelofibrosis , Paraproteinaemia , Waldenstrom’s macroglubunaemia , T-cell lymphomas Hepatic Chronic active hepatitis, Primary biliary cirrhosis, Sclerosing cholangitis Vasculitides , collagen vascular disorders SLE, Systemic sclerosis, Wegener’s granulomatosis , Behcet’s disease, Takayasu’s arteritis Acne and related disorders Acne conglobata , Acne fulminans , Hidradenitis suppurativa , PAPA (recurrent familial arthritis) Autoimmune Thyroid disease, Diabetes mellitus Drugs Colony stimulating factors, Propylthiouracil , Interferon, Geftinib , Isotretinoin Solid organ tumours Colon, Pancreas, Breast, Bronchus, Carcinoid Other dermatosis Neutrophilic dermatosis , Pustular vasculitis , Psoriasis Miscellaneous Sacoidosis , Infections( including HIV and Hep . C), Chronic lung disease, Complement deficiencies( C2, C4, C7), Familial Rook’s textbook of dermatology

36. Classification of PG Morphologically

37. Other types of PG Peristomal PG other types of PG Postoperative PG PATHERGIC PHENOMENON

38. Peristomal PG Pustular PG Vegetative PG Along thoracotomy scar

39. Diagnosis of PG Typical clinical features Exclusion of other cutaneous ulceration diseases Criteria for diagnosis of Pyoderma gangrenosum (classical/ulcerative type)

40. Diagnostic criteria Major criteria (both required) 1. Rapid (usually > 1 cm/day) progression of painful, necrolytic ulceration with an irregular, undermined, violaceous border – usually with a preceding papule, pustule or bulla and pain out of proportion to the size of the ulcerations 2. Exclusion of other causes of ulcerations Minor criteria ( at least two required) 1. (a) History of pathergy (b) Presence of cribriform scarring 2. Presence of disease known to associated ( IBD, polyarthritis , myelodysplasia or leukemia, but monoclonal gammopathy should be added to this list; over all about 50% have an systemic associations 3. Appropiate histological findings 4. Rapid ( at least 50% reduction in size) with oral steroid (1-2mg/day)

41. Differential diagnosis Stasis ulcer Stasis ulcer with visible varicosity Cutaneous PAN Ischemic ulcer Diabetic ulcer

42. Dermatitis artifecta Pressure ulcer Cryptococcus ulcer

43. Mycobacterium marinum Tubercular verruca cutis Mycobacterium ulcerans Basal cell carcinoma Squamous cell carcinoma Leishmaniasis

44. Investigations Routine blood investigations including ESR Australia antigen, anti HCV antibodies Antibody screening : ANA / ANCA Rheumatoid factor Serum protein electrophoresis Swab for culture ASO titre Mantoux test Coagulation screening VDRL ELISA screening for HIV

45. Endoscopy ( upper and lower GI) Vascular studies Bone marrow aspirate examination USG abdomen ( including liver/spleen/lymph nodes) Chest X ray CT scan of thorax, abdomen, brain Skin biopsy

46. Treatments: systemic MEDICATION DOSAGE PREDNISOLONE 0.5 – 1.5 mg/kg/day PO METHYLPREDNISOLONE ( PULSE DOSE) 500 mg – 1 gm IV DAPSONE 50 – 100 mg / day PO CLOFAZIMINE 200 – 400 mg / day PO COLCHICINE 0.3 – 1 mg /day PO MINOCYCLINE 50 – 100 mg bid PO CYCLOSPORIN 3 – 5 mg/kg/day PO TACROLIMUS 0.1 0.3 mg/kg PO MYCOPHENOLATE MOFETIL 500 mg – 1 gm bid PO INFLIXIMAB 5 mg / kg IV

47. Treatments: topical Wet compressess Hydrophilic occlusive dressings Antimicrobial agents Potent topical steroids eg clobetasol propionate 0.01% Topical tacrolimus 0.03% or 0.1% Others Benzoyl peroxide 5- aminosalicylic acid Nitrogen musturd (20% aqueous) Cromogylcate preparations PDGF (platelet derived growth factor) Topical nicotine cream Potassium iodide solution

48. Treatments: intralesional Corticosteroid ( triamcinolone acetonide ) 5 – 10 mg/ml twice a week Ciclosporin

49. Prognosis Poor prognostic factors PG variant (ulcerative PG) Age (> 65 yrs) Sex ( male) Presence of systemic disease Type, dosage and duration of therapy PG have a significant risk of relapse , so long term follow- up is required.

50. Conclusion When leg ulcers fail to respond to treatment or heal in an orderly and timely manner, clinicians should be prompted to conduct further diagnostic investigations, refer to specialists as indicated and ensure a multidisciplinary approach.

51. References Rook’s book of dermatology 8 th edition. Fitzpatrick book of dermatology. Indian association of Dermatologist, Venerologist , and Leprologist textbook of leprosy. Lever’ histopathology of the skin. IADVL journal. JAMA Dermatology journal.

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