What you should know about Vasculitis, Purpura and Food Allergy

Allergic leucocytoclastic vasculitis

The term vasculitis is defined as inflammation of blood vessels. Current classification schemes have been proposed by the American College of Rheumatology in 1990 and in the Chapel Hill classification from 1992, which integrate the size of affected vessels, as well as clinical and histopathological findings.5, 6 Based on current data, cutaneous vasculitis is associated with the following conditions: infection (15%-30%), inflammatory disease (15%-20%), drug intake (10%-15%), and malignancy (5-10%). In 45%-55% of cases, no underlying cause can be identified and therefore are classified as idiopathic.8,9

Histopathology and pathophysiology

“Allergic leucocytoclastic vasculitis”, which was diagnosed in Heidi’s case, is a term delineated from “Cutaneous leucocytoclastic angiitis” defined by the Chapel Hill Classification and describes an angiocentric segmental inflammation, of small vessels of the skin, usually without internal organ involvement. Histological hallmarks are endothelial swelling and fibrinoid necrosis of postcapillary venules, with massive infiltration of neutrophils undergoing fragmentation of nuclei (karyorhexis, leucocytoclasia).7 The pathophysiology of allergic vasculitis starts with deposition of IgG or IgM immune complexes and fibrin in small vessels, mainly at regions with increased hydrostatic pressure. Complement activation by immune complexes leads to attraction of neutrophils, which disintegrate and release lysosomal enzymes and oxygen free radicals. Complement products (e.g. C5a) induce mast cell degranulation with release preformed mediators leading to stasis (histamine, serotonin) and de novo synthesis of proinflammatory cytokines and leukotriens like TNF-a or PGE2, thus perpetuating the pathogenetic process.1, 7

Clinical findings

Acute clinical manifestations of allergic leucocytoclastic vasculitis range from urticae, over papules to vesicles and result in palpable purpura with superficial infarction or ulceration, mostly localized in dependent areas, regions of trauma or under tightly fitting clothes.1 In recent Spanish studies, the frequency of conditions and drugs associated with leucocytoclastic vasculitis were analyzed (Table 3).8, 9 Differences between populations and geographic regions can be assumed.

Table 3. Prevalence of trigger factors in allergic vasculitis8, 9

Reported Foodstuff as elicitor of allergic vasculitis

Foodstuff is mentioned as possible elicitor of allergic vasculitis in reviews and textbooks of Dermatology and Allergy, but rarely considered in clinical practice and is reported only anecdotally in current literature:1, 7, 10 Eisenmann described 2 cases with purpura after oral provocation with rye bread and carrots.3 Also, cutaneous leucocytoclastic vasculitis with concurrent involvement of large joints after ingestion of cow’s milk, hen’s egg, and cocoa products were reported in two pediatric patients.11 Besides food itself, also food additives can provoke vasculitis, as documented by purpura associated with tartrazine and benzoate, with or without concurrent HCV infection and cryoglobulinemia.4, 12

Reported foodstuff as elicitor of other forms of purpura

Besides allergic vasculitis, idiopathic thrombocytopenic purpura (ITP) is another common cause of purpura, which can be caused by antibodies related to foodstuff as well. Reported foods causing ITP include cow’s milk, sesame seeds and cranberry juice.13-15 Also, pathogen-derived toxins, such as shiga-like toxin produced by E. coli O157:H7 (and other toxin-producing strains) are capable of inducing hemolytic uremic syndrome which is - among others - characterized by purpura.16

Diagnosis

Diagnosis of allergic leucocytoclastic vasculitis is based on patient’s history, clinical examination and histopathology. Serology and diagnostic imaging should be used to rule systemic vasculitis. Bleeding disorders including thrombocytopenia and other forms of vasculitis have to be excluded (Table 1). Possible trigger factors of allergic vasculitis (Table 2/Table 3) should be evaluated thoroughly to allow specific therapy.7

Therapy of allergic leucocytoclastic vasculitis

Therapy of allergic leucocytoclastic vasculitis should start with removal or causal therapy of trigger factors. To date no generally accepted gold standard for symptomatic therapy has been defined and almost no double–blind placebo controlled, prospective trials have been published. Topical treatment can be carried out with corticosteroid preparations, bed rest and gradient stockings are proposed as well.7 In more severe cases oral steroids (e.g. prednisolon 60-80mg for 3-5 days) or NSAID have been proposed for first line therapy. Second line therapies include colchicine, dapsone, immunosuppressive agents, antimalarials and IVIg, whereas possible benefits of antihistamines are under debate.1, 2, 7

Verification of foodstuff causal agent in allergic vasculitis

Identification of causal agents in allergic vasculitis induced by foodstuff should combine approaches used for food allergies and vasculitis. Starting with comprehensive history, the possible elicitors should be narrowed down to a limited number of possible causes:17

• Food responsible for the reaction
• Quantity of the food ingested
• The length of time between ingestion and development of symptoms
• Whether similar symptoms occurred when the food was eaten previously
• Whether other factors, such as exercise were necessary for elicitation of symptoms
• When the last reaction to the food occurred

Skin prick testing and measurement of specific IgE should be carried out to evaluate an IgE-mediated process, but can also lead to flares of vasculitis mediated by immune complexes of other specificity. In addition, patch testing can give information on the relevance of suspected foodstuff or additives in food induced vasculitis.18 Absence of symptoms should be achieved in a diagnostic elimination diet, while the final proof of causality and verification of clinical significance can be accomplished by double-blind, placebo controlled food challenge.17, 19

References

1. Fiorentino DF. Cutaneous vasculitis. J Am Acad Dermatol 2003; 48:311-40.

2. Sterry W, Paus R. Vaskulitiden. In: Checkliste Dermatologie. Stuttgart: Georg Thieme Verlag; 2004. p. 269-84.

3. Eisenmann A, Ring J, von der Helm D, Meurer M, Braun-Falco O. [Allergic vasculitis caused by food allergy]. Hautarzt 1988; 39:318-21.

4. Wuthrich B. Adverse reactions to food additives. Ann Allergy 1993; 71:379-84.

5. Hunder GG, Arend WP, Bloch DA, Calabrese LH, Fauci AS, Fries JF, et al. The American College of Rheumatology 1990 criteria for the classification of vasculitis. Introduction. Arthritis Rheum 1990; 33:1065-7.

6. Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994; 37:187-92.

7. Lotti T, Ghersetich I, Comacchi C, Jorizzo JL. Cutaneous small-vessel vasculitis. J Am Acad Dermatol 1998; 39:667-87; quiz 88-90.

8. Sais G, Vidaller A, Jucgla A, Servitje O, Condom E, Peyri J. Prognostic factors in leukocytoclastic vasculitis: a clinicopathologic study of 160 patients. Arch Dermatol 1998; 134:309-15.

9. Garcia-Porrua C, Gonzalez-Gay MA, Lopez-Lazaro L. Drug associated cutaneous vasculitis in adults in northwestern Spain. J Rheumatol 1999; 26:1942-4.

10. Braun-Falco O. Dermatology. Heidelberg; 2004.

11. Businco L, Falconieri P, Bellioni-Businco B, Bahna SL. Severe food-induced vasculitis in two children. Pediatr Allergy Immunol 2002; 13:68-71.

12. Kalinke DU, Wuthrich B. [Purpura pigmentosa progressiva in type III cryoglobulinemia and tartrazine intolerance. A follow-up over 20 years]. Hautarzt 1999; 50:47-51.

13. Caffrey EA, Sladen GE, Isaacs PE, Clark KG. Thrombocytopenia caused by cow's milk. Lancet 1981; 2:316.

14. Arnold J, Ouwehand WH, Smith GA, Cohen H. A young woman with petechiae. Lancet 1998; 352:618.

15. Davies JK, Ahktar N, Ranasinge E. A juicy problem. Lancet 2001; 358:2126.

16. Riemann HP, Cliver DO. Microbial food borne pathogens. Escherichia coli O157:H7. Vet Clin North Am Food Anim Pract 1998; 14:41-8.

17. Sampson HA. 9. Food allergy. J Allergy Clin Immunol 2003; 111:S540-7.

18. Grosshans E, Tomb R. [Skin tests in allergic vasculitis]. Allerg Immunol (Paris) 1992; 24:256-61.

19. Ortolani C, Bruijnzeel-Koomen C, Bengtsson U, Bindslev-Jensen C, Bjorksten B, Host A, et al. Controversial aspects of adverse reactions to food. European Academy of Allergology and Clinical Immunology (EAACI) Reactions to Food Subcommittee. Allergy 1999; 54:27-45.

Allergy field concerned and key words
Food Allergy, Differential diagnosis, Immune complex vasculitis, Pathophysiology, IgG

Summary

We describe the case of a 61 year old woman who suffered from chronic recurrent allergic leucocytoclastic vasculitis with the clinical picture of palpable purpura. A comprehensive screening for the typical elicitors included infectious-, chronic inflammatory- or malignant disease and drug intake, but failed to provide a causal explanation for the vasculitic process. Finally, a relapse following the ingestion of a fruit salad allowed us the directed testing and verification of kiwi fruit as eliciting agent by oral provocation of our patient. Based on this finding, we recommend keeping foodstuff in mind as trigger factor for allergic leucocytoclastic vasculitis, especially in unclear cases which are classified as “idiopathic”.

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