Urticarial vasculitis diagnostic challenge in 2 cases Ahmed Yehia, MD immunolgy
•Download as PPTX, PDF•
1 like•117 views
Urticarial vasculitis diagnostic challenge in 2 cases Ahmed Yehia, MD Immunology, rheumatology and allergy How to approach a case of itching and urticaria and how to interprete skin biopsy
Recommended
More Related Content
Similar to Urticarial vasculitis diagnostic challenge in 2 cases Ahmed Yehia, MD immunolgy
Similar to Urticarial vasculitis diagnostic challenge in 2 cases Ahmed Yehia, MD immunolgy (20)
More from Internal medicine department, faculty of Medicine Beni-Suef University Egypt
More from Internal medicine department, faculty of Medicine Beni-Suef University Egypt (20)
Recently uploaded
Recently uploaded (20)
Urticarial vasculitis diagnostic challenge in 2 cases Ahmed Yehia, MD immunolgy
- 1. Ahmed Yehia, MD Internal Medicine Immunology (Allergy & Rheumatology) Beni-Suef Each itch will itch
- 2. Personal history •N.S.S., 38 years old female patient, borne and living in El-Fashn, married 19 years ago with 5 offspring, the youngest is 2 years old, with no special habits of medical importance.
- 3. Complaint Red itchy & burning skin lesions
- 4. Present history Then they heal with no residual pigmentation. The lesions lasted from a few hours up to more than 2 - 3 days. The condition started 16 years ago by recurrent attacks of red swollen raised sometimes itchy & burning skin lesions, migratory appearing anywhere in the body.
- 5. No obvious precipitating factors were identified but frequency increases in summer.
- 6. •She was on antihistaminics for long periods with fair response and “on and off” course.
- 7. •15 days prior to her presentation to us, she developed right wrist arthralgia.
- 8. No fever, oral or genital ulcers, photosensitivity , malar rash or Raynaud's phenomenon . There were no other mucocutanous manifestations apart from hair loss. No symptoms suggestive of other systems affection.
- 11. So, we have local skin disease. Pruritus Skin lesion Local skin disease Normal skin except itch consequences Systemic disease
- 14. General examination The patient is alert, conscious and oriented to time, place and persons. She has intact recent and remote memory with average mood and intelligence. BP:120/80 mmhg Heart rate:72 beat /min regular with average volume and intact peripheral pulsations. T: 37.2C RR: 16 cycles/minute
- 15. Head, neck, heart, lung and abdomen Examination findings are unremarkable.
- 16. Musculoskeletal examination Normal except tender right wrist joint with no swelling or LOM.
- 17. Mucocutaneous examination •At time of examination, there were wheals over the extremities.
- 18. Urticaria, how to approach? Acute Chronic 6 weeks
- 20. Dermographism
- 21. So, our patient was diagnosed as chronic spontaneous urticaria (CSU).
- 22. Investigations
- 24. Negative ANA 94.2 mg/dl C3 20.6 mg/dl C4 Negative HCV Ab, HBsAg Negative RF 0.94 TSH 112 IU/ml ( up to 100 ) Serum total IgE
- 25. Summary 38 years old lady, with chronic urticaria diagnosed as CSU, hair falling, Rt wrist arthralgia. 1 But she didn’t respond well to antihistamunics for long years with the dermatologists. 2
- 26. What is the differential diagnosis?
- 27. Chronic Urticaria??? Against With Arthralgia Urticarial rash Rash persistence > 24 hours Burning sensation Itchiness Poor response to H1# blokers
- 28. Mostly not Chronic Spontaneous Urticaria
- 29. SLE??? Against With ANA -ve Hair falling ESR, C3, C4: normal Arthralgias No other criteria Urticarial skin rash
- 30. Mostly not SLE
- 31. Cryoglobulinemia??? Against With Rash increases in summer Arthralgias ESR, C3, C4: normal Urticarial skin rash HCV Ab –ve CBC: normal
- 33. What is next?
- 34. Indications of skin biopsy in chronic urticaria 1. Persistence of individual lesion > 24 hours. 2. Pain, burning or tenderness. 3. Petechiae or purpura. 4. Postinflammatory pigmentation after wheal resolution. 5. Poor response to antihistaminics. 6. Pyrexia or other systemic manifestations e.g. arthritis.
- 35. So, we took a skin biopsy from a fresh lesion.
- 36. Pathology Picture is suggestive of Urticarial vasculitis
- 37. CU Urticarial vasculitis -- + Pain and burning + + Pruritus < 24 hours > 24 hours Persistence - + Postinflamatory pigmentation - + Petichae or palpable purpura - + Presence of systemic manifestations Is it too late? Could we have detected it earlier?
- 38. Extracut. affection Complement deficiency Skin Vasculitis Urticaria Classification --- --- --- ++ CSU Urticarial vasculitis, is it the end of the diagnostic journey?!
- 39. Extracutaneos affection Complement deficiency Skin Vasculitis Urticaria Classification --- --- --- ++ CSU +/- --- + ++ NUV Urticarial vasculitis, is it the end of the diagnostic journey?!
- 40. Extracut. affection Complement deficiency Skin Vasculitis Urticaria Classification --- --- --- ++ CSU +/- --- + ++ NUV ++ +++ ++ ++ HUV Urticarial vasculitis, is it the end of the diagnostic journey?!
- 41. Extracut. affection Complement deficiency Skin Vasculitis Urticaria Classification --- --- --- ++ CSU +/- --- + ++ NUV ++ +++ ++ ++ HUV ++++ +++ ++++ ++ HUVS UV represents a continuum of disease, ranging from urticaria with minimal vasculitis, to life- or organ- threatening systemic vasculitis with minimal urticaria.
- 42. Assess for a cause for UV especially HUV CTDs(e.g.,SLE,Sjogren syndrome) Medications (infliximab, glatiramer acetate & the injection of hyaluronic acid.) viruses (particularly hepatitis B & C).
- 43. Assess for a complication for UV especially HUV
- 44. Does differentiation matter a lot? To be aware of a possibility of systemic involvement. To consider searching for specific causes. Treatment plan is completely different.
- 45. Urticaria treatment guidelines •No systemic GCs except in severe exacerbation.
- 46. UV treatment Often difficult to treat & therapy is based upon case reports & small series. Systemic GCs are the mainstay of therapy. Antihistamines are used to manage pruritus. GCs with dapsone, colchicine or HCQ are initial therapy for mild to moderate UV.
- 47. For refractory symptoms or organ- or life-threatening manifestations MMF MTX Azathioprine Cyclosporine. Based on limited data, along with our experience, we use the following agents in order of preference:
- 48. For refractory symptoms or organ- or life-threatening manifestations •We rarely use cyclophosphamide, given the potential toxicity & limited benefit.
- 49. For refractory symptoms or organ- or life-threatening manifestations Rituximab Anakinra Canakinumab Omalizumab As more evidence becomes available, these agents may become preferred.
- 50. Case 2 Personal history •M.F.H., 47 years old male patient, borne & living in Beni-Suef, married since 2000 with 3 offspring, the youngest is 4 years old, smoker (40 pack-year).
- 51. Red itchy skin lesions Complaint
- 52. Present history •The condition started 3 years ago by recurrent attacks of red swollen raised, markedly itchy & burning skin lesions, migratory appearing allover the body including the face and the scalp.
- 53. The lesions don’t improve with multiple antihistaminics & respond only to systemic steroids with frequent relapse on stopping steroid. The single lesion may persist > 24 h. Then they heal with no residual pigmentation.
- 54. No obvious precipitating factors (drugs, infections, foods…….) were identified.
- 55. No fever, oral or genital ulcers, photosensitivity , malar rash or Raynaud's phenomenon . There were no other mucocutanous manifestations. No symptoms suggestive of other systems affection.
- 56. Mucocutaneous examination At time of examination, there were wheals over the extremities.
- 58. What is next?
- 59. Indications of skin biopsy in chronic urticaria 1. Poor response to antihistaminics. 2. Persistence of individual lesion > 24 hours. 3. Petichae or purpura. 4. Presence of systemic manifestations e.g. Pyrexia, arthritis. 5. Postinflammatory pigmentation after wheal resolution.
- 60. Skin biopsy August Superficial perivascular infiltrate of lymphocytes. The epidermis shows focal parakeratosis Diagnosis: Erythema annulare centrifugum, superficial type
- 61. Erythema annulare centrifugum!! • Annular, erythematous lesion • Urticarial-like papule • Enlarges centrifugally, then clears centrally.
- 62. So, we did skin rebiopsy
- 63. What is your diagnosis?
- 65. The hallmark of UV is Leucokytoclastic vasculitis
- 66. The hallmark of UV Leucokytoclastic vasculitis CSU UV
- 69. Guitart, J. J. J. o. t. A. A. o. D. (2008). "“Lymphocytic vasculitis” is not urticarial vasculitis." 59(2): 353. A comment on the previous article
- 70. Histopathologically, UV is defined as a minimum of leukocytoclasia with vessel wall necrosis, with or without fibrinoid deposits, perivascular inflammation, or RBC extravasation. Although findings can be subtle & consist only of interstitial neutrophils or perivascular lymphocytes with extravasated erythrocytes (especially in older lesions), these findings alone do not fulfill the histologic criteria for the diagnosis of UV.
- 71. Leukocytoclasis & fibrinoid deposits are the most important aspects of LCV, as they represent direct signs of vessel damage. A continuum exists in the amount & type of vessel inflammation in UV, ranging from a sparse perivascular infiltrate with no leukocytoclasis to a dense infiltrate with frank leukocytoclasis and fibrin deposition in the most severe forms. These more severe findings, typically with a neutrophilic infiltrate, are seen in patients with HUVS.
- 72. Rarely, lymphocytic, as opposed to leukocytoclastic, vasculitis may be observed.
- 73. • Skin biopsy typically reveals a small-vessel LCV that involves post-capillary venules. • However, it seems that non-specific findings, such as lymphocyte & eosinophil infiltrates are relatively common, when an ‘older’ lesion is biopsied.
- 74. • Often, multiple biopsies are needed to establish diagnosis of LCV, preferably of a wheal < 12 h after eruption. This is, in author’s opinion, the reason why our patient’s skin biopsies were negative for vasculitis and, considering that she already fulfilled Schwarz criteria, we chose not to put her through a third biopsy.
- 75. A novel histopathological scoring system to distinguish UV from CSU • Results: The greatest differences between UV & CSU samples were observed for leukocytoclasia (present in 76% of UV vs. 3.9% of CSU samples; p < 0.0001), erythrocyte extravasation (present in 41.3% of UV vs. 2.0% of CSU samples; p < 0.0001), and fibrin deposits (present in 27.9% of UV vessels vs. 9.7% of CSU vessels; p < 0.0001). Based on these findings, we developed a diagnostic score, the urticarial vasculitis score (UVS), which correctly assigned 37 of 46 cases of UV and 49 of 51 cases of CSU to the previously Puhl V, Bonnekoh H, Scheffel J, Hawro T, Weller K, von den Driesch P, Röwert-Huber HJ, Cardoso J, Gonçalo M, Maurer M, Krause K. Clin Transl Allergy. 2021
- 76. A novel histopathological scoring system to distinguish UV from CSU • Conclusion: Our results suggest that the UVS, a combined quantitative assessment of the three criteria leukocytoclasia, fibrin deposits and extravasated erythrocytes, distinguishes UV from CSU in skin histopathology. The UVS, if validated in larger patient samples, may help to improve the diagnostic approach to UV. Puhl V, Bonnekoh H, Scheffel J, Hawro T, Weller K, von den Driesch P, Röwert-Huber HJ, Cardoso J, Gonçalo M, Maurer M, Krause K. Clin Transl Allergy. 2021
- 77. Timing of the skin biopsy is critical. Classic lesions less than 24 hours old • typically reveal fibrin deposits & neutrophilic infiltration with hemorrhage (caused by extravasation of erythrocytes) & nuclear debris. Soon thereafter • neutrophils are replaced with infiltration of lymphocytes & macrophages & by 48 hours, lymphocytes predominate. Ting, T. V. J. P. C. (2014). "Diagnosis and management of cutaneous vasculitis in children." 61(2): 321-346.
- 78. Our patient • Dependent on high dose steroid. • So, we add cyclosporine A • He may have resistant CSU or missed NUV.
- 79. To further complicate the diagnosis. •In a study, wheals lasted < 24 hours in 57.4% of patients & pain or tenderness was reported by 8.6% of those affected. Extracutaneous features were present in 81%, hypocomplementemia in 11% & abnormalities of other laboratory parameters (e.g., elevated ESR, microscopic hematuria) in 76.6%. Clinical Dermatology, Sixth Edition, 2016, Elsevier Inc.
- 80. IS HUV = SLE?
- 81. UV etiopathogenesis (still undefined) • Immune complex–driven
- 82. UV etiopathogenesis (Immune complex– driven) Activation of the complement cascade Exaggerated production of anaphylatoxins Neutrophil recruitment and activation.
- 83. Pathophysiology
- 85. HUVS (McDuffie syndrome( • Defined as a severe subset of HUV, characterized by multiorgan involvement
- 86. Diagnostic criteria of HUVS Hypocomplementemic urticarial vasculitis syndrome (HUVS) is recognized as a specific autoimmune disorder
- 87. Hypocomplementemic urticarial vasculitis •Patients with UV and hypocomplementemia who do not meet diagnostic criteria for HUVS. cutaneous disease •Plus few or no systemic manifestations. (HUVS)
- 88. EPIDEMIOLOGY • The precise prevalence of UV is unknown due to its rarity. • The incidence in the US population has been found to be 0.5/100,000 person- years. • A Swedish study estimated an annual HUV incidence rate per million inhabitants of 0.7 (95% CI, 0.4- 1.1) with a point prevalence on December 31, 2015, of 9.5/million.
- 89. EPIDEMIOLOGY • Although the proportion between observed cases ofHUV & NUV may depend on setting, for example, dermatology, allergology & rheumatology, according to most published case series, NUV is more common than HUV.
- 90. EPIDEMIOLOGY In a retrospective study on 84 LCV patients in Minnesota (USA), UV accounted for 12% of the total population, with rates in other reports ranging from 9% to 21%. Conversely, UV may represent 2% up to 27% of patients initially presenting with urticaria.
- 91. Epidemiology • The peak reported incidence is in the fourth decade. •The prevalence of UV in patients with chronic urticaria varies from 5% to 20%. CSU UV HUV HUVS NUV • Severity • System involvement
- 92. EPIDEMIOLOGY • Women are more frequently affected especially in the fourth decade. Only rare reports in children have been reported in the literature with UV being diagnosed in approximately 1% of children with vasculitis.
- 93. HUVS (McDuffie syndrome( main differential diagnoses Chronic spontaneous urticaria Bullous pemphigoid IgA (Henoch- Sch€onlein purpura) IgM/IgG immune complex vasculitis Lupus erythematous tumidus Wells syndrome Erythema multiforme Cutaneous mastocytosis Cryopyrin- associated periodic syndromes Coronavirus disease 2019– associated AntiSARS COV 2- vaccine–associated urticarial eruptions
- 94. D.D.: A, Bullous pemphigoid. B, LCV. C, Lupus erythematosus tumidus. D, Wells syndrome. E,Erythema multiforme. F, Maculopapular cutaneous mastocytosis.
- 96. CIU NUV HUV HUVS Dermatology Rheumatology & Immunology
- 97. Key messages Timing of the skin biopsy is critical. UV is a clinicopathologic entity consisting of urticaria & evidence of LCV on skin biopsy. To biopsy or not ( Biopsy is the gold standard in vasculitis diagnosis.) Some dermatology for the rheumatologists And some rheumatology for the dermatologists.
- 98. Urticarial Vasculitis Clinico (Urticaria + 1 of 6 P) Pathologic (Leucytoclastic vasculitis)
- 99. Consider UV and don’t forget. SLE CSU UV Dermatologists Rheumatologists
- 100. Consider the 6 P. Although none is diagnostic. 6 P Pain & tenderness, burning Persistence >24 h Purpura or Petichae Postinflam. Pigment Pyrexia or systemic S or Ss Poor response to H1# UV Biopsy LCV 3 C Classification Cause Complications
- 101. Don’t let the pathology or lab test guide you blindly.
- 102. You are the leader. You are a physician. Use your clinical sense & tools.
- 103. Finally •Each itch Will itch BUT Differs much.
- 104. THANK YOU خيرا هللا جزاكم
- 105. Typical laboratory findings in HUVS ● ESR acceleration ● Hypocomplementemia with low C1q, C3, C4 ● C1q antibodies ● ANA without anti-double-stranded DNA
- 106. Prognosis • UV is a benign & self- limited disease for the majority of patients, although symptoms can last for decades in some individuals.
- 107. Diascopy of urticarial vasculitis skin lesion
Editor's Notes
- A hive or wheal is a circumscribed, erythematous or white, nonpitting, edematous, usually pruritic plaque that changes in size and shape by peripheral extension or regression during the few hours or days that the individual lesion exists. The edematous central area (wheal) can be pale in comparison to the erythematous surrounding area (flare).The evolution of urticaria is a dynamic process. New lesions evolve as old ones resolve. Hives result from localized capillary vasodilation, followed by transudation of protein-rich fluid into the surrounding tissue; they resolve when the fluid is slowly reabsorbed. The edema in urticaria is found in the superficial dermis. Lesions of angioedema are less well demarcated. The edema in angioedema is found in the deep dermis or subcutaneous/submucosal locations.
- Cryoglobulinemia cause cold induced urticaria.
- The association with some disorders in which the antigen-antibody complexes are well defined and the observation that removal of immune complexes by plasmapheresis is temporally associated with the resolution of the urticarial lesions.
- Prednisone in dosages exceeding 40 mg/day is effective. Other medications reported to be effective are indomethacin (25 mg three times daily to 50 mg four times daily), colchicine (0.6 mg two or three times daily), dapsone (up to 200 mg/day), low-dose oral methotrexate, and antimalarial drugs. Cinnarizine was effective in a high percentage of the patients
- from case reports & small case series
- A hive or wheal is a circumscribed, erythematous or white, nonpitting, edematous, usually pruritic plaque that changes in size and shape by peripheral extension or regression during the few hours or days that the individual lesion exists. The edematous central area (wheal) can be pale in comparison to the erythematous surrounding area (flare).The evolution of urticaria is a dynamic process. New lesions evolve as old ones resolve. Hives result from localized capillary vasodilation, followed by transudation of protein-rich fluid into the surrounding tissue; they resolve when the fluid is slowly reabsorbed. The edema in urticaria is found in the superficial dermis. Lesions of angioedema are less well demarcated. The edema in angioedema is found in the deep dermis or subcutaneous/submucosal locations.
- In the deep variant of EAC, the epidermis is usually unremarkable, and a mononuclear cell infiltrate with a sharply demarcated perivascular arrangement is present primarily in the mid and lower dermis. Due to the deeper dermal involvement, the lesions are elevated and are more indurated than in the superficial form of EAC, and they do not have a trailing scale. Some dermatopathologists believe that the deep form may be a manifestation of tumid lupus.
- To the Editor: In the June 2007 issue, Lee et al1 reported 22 patients exhibiting the clinical features of urticarial vasculitis, yet only three of the cases showed leukocytoclastic vasculitis. The authors concluded that the majority of patients with clinical features of urticarial vasculitis have a lymphocytic-predominant vasculitis with eosinophils. The cohort of patients in the study by Lee et al had persistent urticarial lesions lasting longer than 24 hours with two of the following criteria: pain or tenderness; purpura or dusky changes; and resolution with hyperpigmentation. I agree that these criteria define a prolonged and possibly severe urticaria, but they do not define urticarial vasculitis. Pain, tenderness, and some purpuric component with subsequent postinflammatory hyperpigmentation can be observed in urticaria, especially when the patient scratches the pruritic lesions. The histopathologic correlate of pruritus and scratching is erythrocyte extravasation and eventual perivascular hemosiderin deposits. Yet this phenomenon does not qualify as a true vasculitis and must be interpreted cautiously and correlated with the clinical context. Most of the patients in the study did not have histologic criteria of leukocytoclastic vasculitis, nor hypocomplementemia or constitutional symptoms, and therefore probably did not have urticarial vasculitis. The proper nosology of clinical entities is crucial. Otherwise, the conclusions of the study may be wrongly interpreted as “lymphocytic vasculitis, a common finding in urticarial vasculitis.”
- احتمال تاني
- We can’t take a 3rd biopsy. You can depend on clinical judgement.
- Immune complex–mediated & when in response to a known antigen such as a drug, can be classified accordingly as a type III hypersensitivity reaction.
- Current understanding of the pathophysiology of HUV and NUV. In a proportion of HUV cases, an aberrant adaptive immune response leads to the production of anti-C1q autoantibodies directed against the collagen-like tail of C1q, possibly through molecular mimicry with viruses or other factors, among which the most likely are EBV-derived peptides (1A). In NUV (and in a minority of HUV cases without anti-C1q autoantibodies), antibodies against trigger factors such as drugs, bacteria, or viruses may be produced (1B). Whatever the immune complexes (antibodies bound to C1q or to other molecules) (2), the classic complement pathway is activated (3). This in turn determines the release of the anaphylatoxins C3a and C5a, which are responsible for mast cell activation/degranulation (4) and neutrophil (and eosinophil)
- Women comprise 60% to 80% of reported patients. UV has also been described in children; the youngest reported case occurred in a patient 1 year of age.
- Histopathologic evidence of cutaneous leukocytoclastic vasculitis (LCV) of the smallvessels, largely involving the postcapillary venules
- يتفرق دمه بين التخصصات.
- (A) Lesion of urticarial vasculitis on the neck. (B) Diascopy causes erythematous halo to disappear, revealing clinically inapparent purpura.