Tattoo sarcoidosis presenting as abdominal allodynia

A 40-year-old man was referred with left-sided abdominal pain (described as “like broken-glass”) radiating across his abdomen, arthralgias and a mild ileitis endoscopically (not histologically). Clinical examination revealed abdominal allodynia and a focally raised, firm and oedematous tattoo (Figure, A). Serum angiotensin converting enzyme (ACE) was 71 IU/L (reference interval [RI], 20–70 IU/L) and ACE mass was 248 μg/L (RI, 37–211 μg/L). A biopsy of the affected tattoo revealed extensive granulomatous dermal inflammation with well defined “naked” tubercles. Polarisation showed a minute amount of exogenous material superficially, although most of the granulomata did not show refractile foreign material, consistent with cutaneous sarcoidosis (Figure, B). Subsequent investigations excluded inflammatory bowel disease. The pain and elevated tattoo resolved with oral corticosteroids (although it initially relapsed when withdrawn) and subsequently methotrexate 20 mg weekly. Sarcoidal reactions to tattoos have been reported1 with abdominal pain related to small fibre neuropathies manifest by allodynia and hyperaesthesia.2 In one study of patients with cutaneous sarcoidosis treated with methotrexate, lesions completely resolved in 75% of patients.3 The prevailing hypothesis is that tattoo pigments provide chronic antigenic stimulation in genetically susceptible patients, leading to systematised granulomatous hypersensitivity

Characterising the Mucosal and Systemic Immune Responses to Experimental Human Hookworm Infection

The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13) and regulatory (IL-10 and TGF-β) response, with some evidence of a Th1 (IFN-γ and IL-2) response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17) response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases

Effect of Hookworm Infection on Wheat Challenge in Celiac Disease – A Randomised Double-Blinded Placebo Controlled Trial

Background and Aims: The association between hygiene and prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study of experimental infection with the hookworm Necator americanus was undertaken among a group of otherwise healthy people with celiac disease to test the potential of the helminth to suppress the immunopathology induced by gluten

Small bowel endoscopy and coeliac disease

Coeliac disease (CD) is a gluten-responsive, chronic inflammatory enteropathy that shares many features with classical autoimmune diseases. Coeliac disease affects about 1–2% of Caucasians, North Africans and Asians who possess the necessary susceptibility genes encoding HLA DQ2 or HLA DQ8. It is not only unique among the autoimmune diseases in that the precise trigger (gluten from wheat, rye and barley) has been identified, but also in that it has lent itself well to advancements in endoscopic imaging. Since its introduction, flexible endoscopy has allowed tissue to be collected from the small bowel with relative ease and safety, and recently has facilitated direct imaging and sampling of the entire small intestine. It is now fifty years since the Crosby capsule first allowed clinicians the ability to non-surgically biopsy the small bowel leading to an enhanced diagnosis of coeliac disease. The introduction of wireless video capsule endoscopy (VCE), small bowel enteroscopy and in particular double balloon enteroscopy (DBE), have expedited the accurate diagnosis of coeliac disease and its more serious complications such as small bowel adenocarcinoma, refractory coeliac disease type II (RCDII) and enteropathy associated T cell lymphoma (EATL)

Randomised clinical trial: a placebo-controlled study of subcutaneous or intradermal NEXVAX2, an investigational immunomodulatory peptide therapy for coeliac disease

Background Nexvax2 contains three gluten-derived peptides, intended to tolerize coeliac disease patients to gluten. Sequences cover six epitopes that trigger immune activation in human leucocyte antigen-DQ2.5-positive patients, most notably after an initial dose. Patients experience gastrointestinal symptoms with increases in serum interleukin-2. Consistent with Nexvax2's induction of non-responsiveness, reactivity disappears after repeated doses, or is avoided with gradual dose escalation. Early clinical trials used intradermal dosing, but pharmacokinetics and rapid onset of effect suggest that subcutaneous delivery may also be effective. Aims To document the relative bioavailability of Nevax2 peptides after subcutaneous and intradermal dosing, and the tolerability and ability of subcutaneous dosing to induce non-responsiveness to Nexvax2 peptides. Methods A randomised, double-blind, placebo-controlled study was conducted to assess plasma pharmacokinetics after subcutaneous and intradermal Nexvax2 dosing in HLA DQ2.5-positive patients, who had symptoms after an oral gluten challenge. Randomisation was to semi-weekly Nexvax2 (n = 12) or placebo (n = 2) injections, over a 5-week subcutaneous dose escalation and 2-week maintenance period, the latter with four doses of 900 mu g, two subcutaneous and two intradermal. Post-dose circulating peptide and interleukin-2 levels were assessed. Investigators recorded adverse events experienced by patients. Results Subcutaneous dosing resulted in slightly greater exposure. Interleukin-2 responses were seen with the gluten challenge but not after subcutaneous or intradermal dosing of 900 mu g. Adverse events were generally mild and self-limited. Conclusions Subcutaneous and intradermal dosing of Nexvax2 yield similar bioavailability of constituent peptides; subcutaneous dose escalation avoids an immune response to dominant gluten epitopes