Delayed hypersensitivity reactions to iodinated contrast media: A diagnostic approach by skin tests.

BACKGROUND: Adverse drug reactions to iodinated contrast media (ICM) have risen due to their increasing use in x-ray-based imaging modalities. Delayed hypersensitivity reactions are mainly caused by nonionic monomeric compounds and represent an issue impacting the diagnostic-therapeutic pathways of cancer, cardiology and surgery patients. OBJECTIVES: To prospectively evaluate the usefulness of skin tests in delayed hypersensitivity reactions to ICM and to evaluate the tolerability of iobitridol, a monomeric nonionic low osmolality compound, as a possible safe alternative. METHODS: Patients with delayed hypersensitivity reactions to ICM referred to us from 2020 to 2022 were prospectively enrolled in the study. All patients underwent patch test and, if negative, intradermal test with the culprit ICM and iobitridol as alternative. RESULTS: A total of 37 patients (females 24, 64.9%) were enrolled in the study. Iodixanol and iomeprol were the most frequently involved ICM (48.5% and 35.2%, respectively); 62.2% of patients presented maculopapular eruption, while 37.8% reported delayed urticaria-like rash. Skin tests resulted positive to the culprit ICM in 19 patients (51.4%), 16 to patch test and 3 to intradermal test. Skin tests with iobitridol, tested as alternative, resulted positive in 3/19 patients (15.8%). All 16 patients with negative results to iobitridol were administered this ICM and tolerated it. CONCLUSIONS: In at least half of patients, delayed-type hypersensitivity was demonstrated by skin tests, particularly by patch test. This diagnostic approach resulted simple, cost-effective and safe, not only to confirm the culprit ICM but also to identify iobitridol as feasible alternative.

A Histologic Timeline of a Delayed Hypersensitivity Reaction after the COVID-19 Pfizer Booster.

A 54-year-old man presented with worsening bilateral rashes on legs and arms 7 days after receiving his BNT162b2 mRNA COVID-19 (Pfizer) vaccine booster. He developed burning on his palms about 5 days after receiving the booster. On day 6, he observed significant edema on his fingers and palms in addition to thin erythematous papules on his forearms. On day 7, he developed edema on his bilateral dorsal feet, and thin erythematous plaques on his shins. He stated that the rashes were pruritic. He had no rashes following the first two doses of the Pfizer vaccine. He denied having any history of skin disease, autoimmune disease, or allergies. Physical examination revealed multiple thin erythematous papules coalescing into thin plaques on his flexor forearms, and thin erythematous plaques on his dorsal feet (Figure 1). Three 4-mm punch biopsies were performed on his left flexor forearm. The biopsies were carried out at papules present for different lengths of time. Papules at biopsy sites "A," "B," and "C" were present for approximately 24-36 hours, 12-18 hours, and 3-6 hours, respectively (Figure 1).

Trunnionosis and metal wear causing metal hypersensitivity: 2 sides of the same coin?

Metal hypersensitivity (MHS) and trunnionosis are being looked at more frequently. Both entities pose a difficult concern for surgeons and patients alike. This commentary highlights the similarities and differences between the 2 conditions. When a surgeon suspects either MHS or trunnionosis, both should be considered in the differential diagnosis. Both conditions are rare and should be considered a diagnosis of exclusion. The commentary proposes an outline on how to diagnose and treat the 2 entities.

COVID-19: Is there a role for Western blots and skin testing for determining immunity and development of a vaccine?

Infection with the virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) stimulates an immune response which can serve as a marker for current or past exposure to this pathogen, and possibly for resistance to re-infection. This response to COVID-19 can be monitored based on the production of antibodies, and thus, serologic tests have become available for diagnostic purposes. Despite progress in this area, concerns have been raised that too many of the commercially available serologic detection systems are not completely reliable. To address this issue, Western blots should be considered for confirming a positive or borderline-positive result from a screening test, such as an ELISA. An additional benefit of Western blots would be to identify antigens that could form the basis for developing a vaccine. Little is known about the cell-mediated immune response against COVID-19. One way to address this would be to use skin testing to measure the delayed-type hypersensitivity response in patients recovering from COVID-19.

Lazarine leprosy: A unique phenomenon of leprosy.

Leprosy, a chronic granulomatous disease, has been known since ages but even today continues to baffle the clinicians with a wide spectrum of clinical, histopathological, and immunological characteristics. Leprosy reactions are mainly of two types, namely, Type 1 and Type 2. In Type 1 leprosy reaction, the preexisting lesions become erythematous, edematous, and rarely ulcerate. Ulcerating Type 1 reaction is called lazarine leprosy. Ulcerations may occur in borderline tuberculoid (BT) pole or borderline lepromatous pole but more common in BT pole. In this postelimination era of leprosy, we report an interesting case report of BT Hansen's disease with Type 1 lepra reaction with ulceration, namely, lazarine leprosy.

Sabra dermatitis: combined features of delayed hypersensitivity and foreign body reaction to implanted glochidia.

A striking dermatitis referred to by its colloquial designation of sabra dermatitis is associated with glochidia inoculation from the Opuntia cactus commonly known as the prickly pear. We report a 45-year-old woman who had an unexpected encounter with a cactus plant during a trip to Texas. She brushed up against the plant and was aware that she had been inoculated with several spines of the plant. Five days later she developed erythematous papules on the digits accompanied by swelling. The biopsy showed a very striking granulomatous reaction pattern within the dermis. There was a linear pattern of necrobiosis, likely representing a tract of inoculation injury palisaded by histiocytes including multinucleated forms. This necrobiotic tract demonstrated retained glochidia, each measuring roughly 40 to 70 microns in diameter. The nature of the inflammatory response is one that combines features of classic delayed hypersensitivity and an innate foreign body response. The glochidia are capable of eliciting a T cell mediated immune response; it is reasonable to assume that a Th1 cytokine signal is responsible for the unique pattern of inflammation including the secondary influx of neutrophils and relative lack of tissue eosinophilia.

Delayed-type Hypersensitivity to Metals in Newly Diagnosed Patients with Nonischemic Dilated Cardiomyopathy.

The causes of nonischemic dilated cardiomyopathy are classified as genetic or nongenetic, but environmental factors such as metal pollutants may interact with genetic susceptibility. The presence of metal particles has been detected in the myocardium, including in those patients with dilated cardiomyopathy. It is also known that hypersensitivity reactions can induce inflammation in tissue. The present study aimed to verify if metal-induced delayed-type hypersensitivity is present in patients with nonischemic dilated cardiomyopathy. The patient group consisted of 30 patients with newly diagnosed dilated cardiomyopathy; the control group comprised 41 healthy subjects. All patients and control subjects provided blood samples for lymphocyte transformation testing (MELISA®) to assess possible hypersensitivity to seven common metals. Specific exposure to metals was based on interview data. Results showed that exposure to cadmium and lead (p = 0.0002), aluminum (p = 0.0006), nickel (p = 0.0012), and chromium (p = 0.0065) was more often reported by patients than controls. The patients also had significantly more frequent hypersensitivity reactions to mercury (26.7% vs. 7.3%, p = 0.014624), nickel (40% vs. 12.2%, p = 0.02341), and silver (20% vs. 4.8%, p = 0.025468) than the control group. Patients with dilated cardiomyopathy had greater exposure to certain metals compared with healthy controls. Hypersensitivity to metals was more frequent in patients with dilated cardiomyopathy, suggesting a possible association that warrants further investigation.

Higher Prevalence of Nickel and Palladium Hypersensitivity in Patients with Ulcerative Colitis.

BACKGROUND: The etiology of ulcerative colitis (UC) remains elusive even though many genetic and environmental pathogenic factors have been reported. Aberrant inflammatory responses mediated by specific subsets of T cells have been observed in ulcerative lesions of UC patients. OBJECTIVES: To elucidate the involvement of a delayed-type hypersensitivity reaction in UC, we focused on dental metal hypersensitivity, a T cell-mediated, delayed-type allergic reaction that causes oral contact mucositis and systemic cutaneous inflammation. METHOD: We recruited 65 Japanese UC patients and 22 healthy controls (HC) and used the in vitro lymphocyte stimulation test to quantify their sensitivity to zinc, gold, nickel, and palladium - the metals that have been widely used in dentistry. All subjects were users of metallic dental implants and/or prostheses containing zinc, gold, nickel, and/or palladium as major constituents. RESULTS: Sixty percent of the UC patients were hypersensitive to at least one metal species, whereas 32% of the HC were hypersensitive to only a single metal species. The overall incidence of metal hypersensitivity was significantly higher for UC patients than for HC. Furthermore, a significantly greater proportion of UC patients were hypersensitive to nickel or palladium. The severity of the sensitivity to nickel and palladium was also significantly greater for UC patients than for HC. CONCLUSIONS: This pilot study demonstrates that UC patients have a significantly higher incidence of hypersensitivity to nickel and palladium, suggesting the possible involvement of dental metal hypersensitivity in UC pathogenesis.

Are Adverse Events Attributed to Essure Associated With Nickel Sensitization?

BACKGROUND: Essure is an effective method for hysteroscopic sterilization. Reports of adverse effects, the underlying mechanisms of which are unknown, have increased in recent years. OBJECTIVE: The aim of the study was to determine whether there is a relationship between adverse events attributed to Essure and nickel sensitization. METHODS: Patients presenting alleged adverse reactions to Essure were referred for nickel patch testing before removal. Data regarding medical history of nickel sensitization and symptoms attributed to Essure were collected. Dimethylglyoxime spot tests were performed on the explanted Essure. There was a follow-up at 3 months to evaluate whether there is improvement of the symptoms after Essure removal. CONCLUSIONS: Nickel sensitization via the classic delayed hypersensitivity pathway did not seem to be responsible for adverse events attributed to Essure. Among systemic symptoms reported, extracutaneous symptoms had the highest prevalence. Systemic contact dermatitis to nickel could not be ruled out in one case.

A Systematic Review of the Literature of Delayed Inflammatory Reactions After Hyaluronic Acid Filler Injection to Estimate the Incidence of Delayed Type Hypersensitivity Reaction.

BACKGROUND: Hyaluronic acid (HA) dermal filler injection is believed to be a safe procedure. However, with the increase in the number of performed procedures and indications, the number of product-related complications, especially delayed inflammatory reactions, has also increased. Delayed-type hypersensitivity (DTH) reaction is one of these delayed inflammatory reactions, which is preventable by performing a pretreatment skin test. OBJECTIVES: The authors sought to find the incidence of delayed inflammatory reactions and DTH reaction after HA injection and to determine whether a pretreatment skin test is worthwhile to be performed. METHODS: The authors conducted a systematic literature review of all the relevant prospective studies, retrospective studies, and case reports on delayed inflammatory reactions and DTH reaction after HA filler injection. RESULTS: The incidence of delayed inflammatory reactions calculated from the prospective studies was 1.1% per year, and that of possible DTH reaction was 0.06% per year. Most retrospective studies estimated a percentage of delayed inflammatory reactions of less than 1% in 1 to 5.5 years. The incidence of DTH reaction would be lower than that. Among all the DTH cases reported, only about 5% of them were proven to be genuine DTH reactions. CONCLUSIONS: The incidence of both delayed inflammatory reactions and DTH reaction is low. There is evidence that genuine DTH reactions caused by HA fillers approved by the Food and Drug Administration do exist. This adverse event can be prevented by performing a pretreatment skin test. However, the incidence of DTH reaction is so low that the pretreatment skin test is not mandatory if Food and Drug Administration-approved HA fillers are used.

Pediatric lichen planus pigmentosus possibly triggered by mercury dental amalgams.

Lichen planus pigmentosus is uncommon in childhood and its treatment is often challenging. We report a case of cutaneous lichen planus pigmentosus in a 10-year-old boy, without oral mucosal involvement, two months after an amalgam dental restoration. The diagnosis was based on the histopathological examination of a skin biopsy, the positive patch test to mercury, and the improvement after amalgam removal. Our case report suggests that metal allergy may play a role, and amalgam replacement may be followed by clinical improvement.

Two case reports of delayed-allergic reactions to clindamycin confirmed with a positive lymphocyte transformation test.

Summary: Clindamycin is widely used in the prophylaxis and treatment of infections due to its broad spectrum of antimicrobial activity. Hypersensitivity to clindamycin seems to be not very common (less than 1% of drug-allergic reactions) and it mostly appears as delayed T-cell mediated. For the diagnosis, skin testing is considered to be highly sensitive and rather safe, but cutaneous and systemic reactions have been described. Provocation test is considered the gold standard. However, it includes the possibility of severe reactions. We reported two cases of delayed allergic reaction to clindamycin, confirmed with a positive lymphocyte transformation test, showing this in vitro test like a promising diagnostic method because of its usefulness and safety.

Diagnosis of Metal Hypersensitivity in Total Knee Arthroplasty: A Case Report.

Delayed type hypersensitivity (DTH) reactions are considered infrequent complications in arthroplasty, but have been recognized to be associated with devastating morbidity and substantial decrease in quality of life of affected patients. Chronic inflammation of artificial joints and associated loss of peri-implant bone often require revision surgery. Methods for the diagnosis of implant-related DTH are available but infrequently considered to the full extent. Sequential diagnostics based on exclusion of septic complications, local and systemic metal level determination, lymphocyte transformation testing (LTT), and local T cell subset analysis are required for an unequivocal DTH diagnosis. Here, we report on a patient with a history of chronic rheumatoid arthritis and an unfavorable outcome of unilateral knee arthroplasty. This case illustrates pitfalls and difficulties in the course of recurrent inflammation following joint replacement. In the early course, suspicion of low-grade bacterial infection led to three two-stage revisions. Afterwards, the joint was proven to be sterile. However, metal level quantification revealed release of especially cobalt and chromium from the joint, LTT indicated persisting cobalt and nickel sensitization and subset analysis of T cells from the synovium suggested DTH as a root cause for the inflammatory symptoms. This report aims to recommend the depicted diagnostic algorithm as an adequate tool for future DTH detection. Yet, systemic to local subset ratios for effector memory and regulatory T cells should be derived from sufficient patient numbers to establish it as a diagnostic marker. Moreover, future prospects regarding implant-related DTH diagnostics are discussed. Therapeutic options for the portrayed patient are proposed, considering pharmaceutical, cell-therapeutic and surgical aspects. Patients who experience peri-implant inflammation but do not have obvious mechanical or infectious problems remain a diagnostic challenge and are at high risk of being treated inadequately. Since potentially sensitizing materials are regularly used in arthroplasty, it is essential to detect cases of acute DTH-derived inflammation of an artificial joint at early postoperative stages. This would reduce the severity of inflammation-related long-term consequences for affected patients and may avoid unnecessary revision surgery.

Sonographic features of vaccination granulomas in children with delayed-type hypersensitivity to aluminum.

In this article, we report the sonographic features of vaccination granulomas in three children sensitized to aluminum. Although the recognition of the vaccination granuloma relies on the clinical examination, misdiagnosis is frequent, leading to distressful procedures or prolonged antibiotic administration. In all our cases, sonography revealed a teardrop-shaped echogenic central structure, suggesting the deposition of aluminum crystals along the route of administration with consequent subcutaneous degenerative changes, and a surrounding hypoechoic cap, which reflects the changeable inflammatory reaction and the granuloma formation.

Type IV Cell-Mediated Hypersensitivity Reaction Caused by Titanium Implant Following Double Calcaneal Osteotomy and First Metatarsal-Cuneiform Arthrodesis: A Case Report and Review of the Literature.

Because of their inert character and desired biocompatibility, titanium implants have been universally accepted as safer alternatives to the conventional stainless steel orthopedic implants; however, recent emergence of type IV hypersensitivity reactions to titanium have included eczema, contact dermatitis, a prolonged febrile state, sterile osteonecrosis, and impaired fracture and wound healing. This report presents a patient with postoperative incision dehiscence and devascularization of surfaces in contact with titanium hardware after undergoing a double calcaneal osteotomy and a first metatarsal-cuneiform arthrodesis using titanium alloy implants. Titanium hypersensitivity was confirmed in this case through standard allergy patch testing by a board-certified immunologist. Complete healing occurred after diagnosis of the titanium allergy and hardware explant. To our knowledge, this is one of a few known allergies to titanium implants after foot and ankle surgery.