Gianotti–Crosti Syndrome Following Childhood Vaccinations

Abstract: A 19‐month‐old boy was evaluated for a skin eruption after recent vaccinations. Clinical and histopathologic findings supported a diagnosis of Gianotti–Crosti syndrome (GCS). This case report examines the link between GCS and vaccinations, particularly the diphtheria, tetanus, and pertussis vaccine and the varicella virus live vaccine.     

Pediatric Wells syndrome (eosinophilic cellulitis) after vaccination: A case report and review of the literature

A 4‐year‐old boy presented with erythematous vesicular plaques, ulceration, edema, and pruritus on the left foot and ankle 10 days after receiving the tetanus, diphtheria, pertussis, and polio; measles, mumps, rubella, and varicella; and hepatitis A/B vaccines. Biopsy showed eosinophilic infiltrates and flame figures, suggesting Wells syndrome. Patch testing showed a 1+ reaction to neomycin and aluminum hydroxide, with a recall reaction of Wells syndrome of the feet bilaterally. We report a rare case of pediatric Wells syndrome triggered by nonthimerosal vaccine components confirmed by patch testing.     

Gianotti-crosti syndrome after childhood vaccination

A 19-month-old boy was evaluated for a skin eruption after recent vaccinations. Clinical and histopathologic findings supported a diagnosis of Gianotti-Crosti syndrome (GCS). This case report examines the link between GCS and vaccinations, particularly the diphtheria, tetanus, and pertussis vaccine and the varicella virus live vaccine.     

Cutaneous Adverse Reactions Following Anti-Infective Vaccinations

Although widely administered, anti-infective vaccinations are rarely responsible for cutaneous adverse effects. In this context, hepatitis B and bacillus Calmette-Guerin vaccines are the most frequently incriminated products. Cutaneous adverse effects are less frequently encountered following administration of vaccines against varicella, diphtheria/tetanus/pertussis (primary and booster doses), measles, poliomyelitis, rubella, pneumococcus, tick-borne encephalitis, smallpox, Meningococcus and influenza. The adverse effects can occur at the site of or at a distance from the injection. The patho-mechanisms of local adverse cutaneous reactions include predominantly nonspecific lymphoid or granulomatous reactions. Allergic reactions to the vaccine strain, adjuvants, conservatives or other components are less frequently involved in local vaccine adverse effects. Systemic reactions are mainly mediated by immediate type or immune complex-related allergic reactions to toxoid-, ovalbumin-, gelatin- or pneumococcal-containing vaccines. Systemic reactions are sometimes related to a specific vaccine strain. Other cutaneous reactions may also occur through unknown patho-mechanisms. No vaccine type or strain is specifically associated with a particular type of cutaneous adverse effect. This article presents seven case reports of cutaneous adverse effects following anti-infective vaccination then reviews the relevant literature on this subject.     

Effect of therapeutic integrin (CD11a) blockade with efalizumab on immune responses to model antigens in humans: results of a randomized, single blind study

Efalizumab is a humanized monoclonal CD11a antibody approved for treatment of psoriasis. Its immunomodulatory effects led us study how immune responses are modified and the possible consequences for vaccinations in clinical practice. This was a randomized, single-blind, placebo-controlled, parallel-group study of 12 weeks of subcutaneous efalizumab treatment of patients with moderate psoriasis. Bacteriophage phiX174 was used as a model neoantigen to assess T-cell-dependent humoral immunity. Tetanus booster vaccine, pneumococcal vaccine, and intracutaneous skin tests were administered to further evaluate humoral and cellular immune responses. During efalizumab treatment, both primary and secondary antibody responses to phiX174, including IgM/IgG isotype switch, were reduced. There appeared to be na?ve T-cell anergy to a neoantigen (phiX174) during active CD11a blockade, without tolerance to the antigen after efalizumab withdrawal. Secondary humoral immune responses to tetanus booster during treatment were reduced, but antibody titer increases led to protective levels. Responses to pneumococcal vaccination 6 weeks after withdrawal from efalizumab were not affected. Cellular immune responses to intracutaneous recall antigens were reduced during treatment and returned to pretreatment conditions after withdrawal. These results expand our knowledge of how immune responses are modulated in humans by CD11a blockade and have implications for vaccinations of patients treated with this agent.     

Bullous Eosinophilic Cellulitis in a Child Treated with Dapsone

Abstract: Eosinophilic cellulitis, or Wells syndrome, is a rare but well‐described condition in which bullous lesions are uncommon, especially in childhood. We report a case of bullous eosinophilic cellulitis recalcitrant to steroid therapy in a 9‐year‐old boy who was successfully treated with oral dapsone.     

Treatment of eosinophilic cellulitis (Wells syndrome) – a systematic review

Eosinophilic cellulitis (Wells syndrome) is a rare inflammatory skin disease defined by erythematous, tender, sometimes urticarial plaques, possibly with vesicles and bullae, and granulomatous eosinophilic infiltrates in the dermis. Usually the disease has a benign course with spontaneous remission within a few weeks. Nevertheless, recurrences are quite frequent and may occur for several years. The objective of this study was to review the so far reported treatment options for Wells syndrome in a systematic manner. This systematic review is based on a search on Medline, Embase and Cochrane Central Register for English and German articles from 1970 to 2015. Advices on the treatment of Wells syndrome are limited predominately to case reports or to small case series. There are no randomized controlled trials, and control groups are missing. A variety of treatment options for Wells syndrome were reported including topical and systemic corticosteroids, antihistamines, cyclosporine, dapsone, azathioprine, griseofulvin, doxycycline, minocycline, antimalarial medications, oral tacrolimus/topical tacrolimus, sulfasalazine, interferon alpha and gamma, TNF alpha inhibitors, colchicine and PUVA therapy. As well‐designed, randomized controlled trials are missing, no guidelines for the treatment of this disease can be given. Due to the small number of patients and the frequent misdiagnosis of this clinical entity, the aim of this systematic overview is to call attention to this rare condition and to help clinicians to diagnose and treat Wells syndrome effectively. Due to the good prognosis and tendency to resolve, systemic treatment should be limited to cases resistant to local therapy or with widespread lesions.     

Eosinophilic dermatoses

Eosinophilic dermatoses are a heterogeneous group of diseases, characterized by an eosinophil‐rich infiltrate and/or degranulation of eosinophils. Blood eosinophilia may be an associated feature. Typical, albeit not specific histological findings include ‘flame figures’, which are caused by the accumulation of cationic proteins released by eosinophils and subsequent collagen denaturation. “Classic” eosinophilic dermatoses include eosinophilic cellulitis (Wells syndrome), granuloma faciale, eosinophilic fasciitis (Shulman syndrome) and eosinophilic folliculitis (Ofuji disease). In addition, there is a multitude of skin diseases that present with varying degrees of eosinophilic infiltration. These include atopic dermatitis, bullous pemphigoid, urticaria, allergic contact dermatitis, prurigo nodularis, arthropod bite reaction, parasitic infections, and drug hypersensitivity. Even though these disorders share a common characteristic (tissue eosinophilia), they differ greatly in their clinical presentation.     

Delayed‐type hypersensitivity to vaccine aluminum adjuvant causing subcutaneous leg mass and urticaria in a child

A 3‐year‐old girl presented with a 7‐month history of a waxing and waning left thigh mass associated with pruritus and erythema at the site of two previous DTaP‐HepB‐IPV vaccinations. Patch testing was positive to aluminum chloride, supporting a diagnosis of vaccine granuloma secondary to aluminum allergy; her symptoms had been well controlled with antihistamines and topical steroids. Injection site granulomas are a benign but potentially bothersome reaction to aluminum‐containing immunizations that can be supportively managed, and we encourage strict adherence to the recommended vaccine schedule in this setting. Patch testing is a sensitive, noninvasive diagnostic tool for patients presenting with this clinical finding, and dermatologist awareness can prevent unnecessary medical examination and provide reassurance.     

Hay‐Wells syndrome in a child with mutation in the TP73L gene

Hay‐Wells syndrome is a rare form of ectodermal dysplasia, also known as AEC syndrome (Ankyloblepharon filiforme adnatum, Ectodermal effects, Cleft lip/palate). It is inherited in an autosomal dominant fashion with variable expression, featuring congenital abnormalities of skin, hair, teeth, nail, eccrine and mucous glands. We present a three‐month‐old boy, born to unaffected parents, with typical clinical findings of AEC syndrome. In this boy, a mutation Ile537Thr (c.1610C>T) in the sterile alpha motive (SAM) domain of the TP73L (p63) gene was detected. Because of the broad spectrum of related syndromes such as Rapp‐Hodgkin syndrome, Bowen‐Armstrong syndrome, CHAND syndrome and epidermolysis bullosa hereditaria, the diagnosis of AEC should be base don both clinical findings and genetic analysis.     

Wells syndrome and its relationship to Churg–Strauss syndrome

Background Wells syndrome has been described as an inflammatory disorder based on typical clinical appearance combined with the histopathological presence of eosinophilic infiltrates and flame figures in the absence of vasculitis. Churg–Strauss syndrome, on the other hand, is primarily a diffuse, necrotizing vasculitis but is also typically displaying eosinophils and flame figures. Despite several parallels, the present understanding of these two diseases excludes any pathogenetic relationship. Methods We describe the clinical course and histopathological appearance of three patients who had initially been diagnosed with Wells syndrome that developed into Churg–Strauss syndrome during the course of their disease. Results The clinical presentation of all three patients led to the diagnosis of Wells syndrome by independent specialists. Histopathology showed an eosinophilic infiltrate and flame figures next to features of leukocytoclastic vasculitis. Detailed examination revealed asthma bronchiale and additional symptoms indicating Churg–Strauss syndrome. The initial diagnosis of Wells syndrome had to be revised to Churg–Strauss syndrome. Conclusion We conclude that Wells syndrome could be the starting point of a pathogenetic process that might reach its maximum in Churg–Strauss syndrome. As a clinical consequence, patients with Wells syndrome should be evaluated and followed for Churg–Strauss syndrome.     

Eosinophilic leukocytoclastic vasculitis — a spectrum ranging from Wells’ syndrome to Churg-Strauss syndrome?

Background

Wells’ syndrome is defined as an inflammatory disorder with the histopathological presence of eosinophilic infiltrates and flame figures in the absence of vasculitis. Eosinophilic leukocytoclastic vasculitis shows eosinophilic infiltrates in combination with vasculitic changes. And Churg Strauss Syndrome comprises all three characteristics — eosinophilic infiltrates, vasculitis and flame figures.

Objective

To determine whether these three diseases are distinct entities or different manifestations of a similar clinicopathologic process.

Method

Histopathological samples and clinical courses of 17 patients with eosinophilic infiltrates, flame figures and clinical features of Wells’ syndrome were re-evaluated. Histopathologically, we focused on the presence or absence of vasculitic features. Clinically, we included only patients who were diagnosed with Wells’ syndrome at least once in the course of their disease.

Results

4 patients were finally diagnosed with Wells’ syndrome, 5 with eosinophilic leukocytoclastic vasculitis and 6 with Churg Strauss syndrome. Further, we had one case of an overlap between Wells’ syndrome and eosinophilic vasculitis and one case of Wegener granulomatosis. Vasculitic features were found in the samples of all patients.

Conclusions

Histologically, we find vasculitic features in typical presentations of Wells’ syndrome. Clinically, we find typical features of Wells’ syndrome in patients finally diagnosed with eosinophilic leukocytoclastic vasculitis or Churg Strauss syndrome. Furthermore, we have observed and formerly reported 3 patients with progression from Wells’ syndrome to Churg Strauss syndrome. Thus, we assume that eosinophilic leukocytoclastic vasculitis might form a bridge between Wells’ syndrome and Churg Strauss syndrome.

     

Aluminum granuloma in a child secondary to DTaP‐IPV vaccination: A case report

Reports detailing the acute formation of aluminum granulomas, which can cause persistent, intensely pruritic nodules secondary to the administration of aluminum‐containing vaccines, are infrequently described in medical literature. To our knowledge, this is the first report describing the development of an aluminum granuloma causing a persistent, pruritic nodule at the injection site following the administration of the DTaP‐IPV vaccine. We present the case of a 6‐year‐old girl who developed a severely pruritic subcutaneous nodule on her anterior right thigh at the injection site three weeks after the administration of the aluminum‐containing DTaP‐IPV (Kinrix) vaccine. The nodule was eventually excised 14 months after its initial appearance, after which her symptoms resolved. Histologic inspection demonstrated a dense, deep dermal and subcutaneous nodular mixed infiltrate of lymphocytes, histiocytes, and eosinophils, with germinal center formation. The bluish, amphophilic granular cytoplasm found in most of the histiocytes is a characteristic feature of “aluminum granulomas.” This adverse reaction should be considered in any patient presenting with similar findings in the weeks following a DTaP‐IPV vaccination or other aluminum‐containing vaccines. Furthermore, the self‐limiting tendency of these nodules should not preclude affected patients from any future vaccinations, though vaccines without aluminum should be preferentially selected when possible.     

Wells综合征七例临床病理分析

目的 探讨Wells综合征的临床及病理特征和治疗情况。方法 回顾性分析7例Wells综合征的临床及病理资料。结果 7例患者中,皮损分别位于双下肢（4例）、背部（1例）、面部和躯干（1例）及臀部（1例）;临床表现为蜂窝织炎样（3例）、荨麻疹样（1例）、环状红色斑块（1例）和丘疹结节（2例）。组织病理学检查均示真皮内大量嗜酸粒细胞浸润,伴有“火焰征”,3例同时伴有血管炎改变。7例患者均无明显的发病诱因。3例给予小剂量糖皮质激素和雷公藤多苷口服,皮损基本消退。 结论 Wells综合征具有多种临床表现,组织学上具有特征性,系统性糖皮质激素和雷公藤多苷治疗有效。     

Polycythemia vera revealed by Wells syndrome

BACKGROUND: Wells syndrome is an eosinophilic dermatosis that is mainly reported in association with infections or insect bites, and more rarely during haematological disorders. CASE REPORT: A 32 year-old woman presented several recurrent episodes of massive swelling and erythema papulo-nodular inflammatory plaques on the buttocks that spontaneously resolved. The biopsy revealed marked infiltration of the dermis with eosinophils suggesting Wells syndrome. Examination found an isolated hepatosplenomegaly with true polycythemia and a myeloproliferative disorder. The diagnosis of Vaquez disease was made. DISCUSSION: Wells syndrome is a distinctive disease entity with a wide polymorphism of clinical and histological features, unspecific, and varying depending on the age of the lesions. Various triggering factors are involved, but this syndrome may also reveal hematological disorders. Cutaneous manifestations often occur before the hematological diagnosis, but are frequently misdiagnosed. Only two other cases of Wells syndrome associated with Vaquez disease have been reported. Our case report underlined the importance of systematic research for an hemopathy in Wells syndrome, especially in young patients.     

Persistent hypereosinophilia with Wells syndrome

Since Wells and Smith first described cases of eosinophilic cellulitis (Wells syndrome; WS) in 1979, it has been noted that some but not all patients with WS present with eosinophilia. In the face of idiopathic persistent eosinophilia patients will also then fall within the hypereosinophilic syndrome (HES), which represents a multifarious spectrum of disorders of varying severity, causes and outcomes. In this article we propose that patients who present within the HES spectrum with cutaneous findings of WS and with no extracutaneous disease be classified as having ‘persistent hypereosinophilia with Wells syndrome’ (PHEWS).     

Wells syndrome

A rare eosinophilic dermatosis, Wells syndrome, also referred to as eosinophilic cellulitis, is characterized by great clinical variability. Typical findings include infiltrated erythematous plaques arising on the extremities. Lesions initially resemble erysipelas/cellulitis, however, they do not improve with antibiotic treatment. Eosinophilic cellulitis is a diagnosis of exclusion that may only be made over the course of the disease, taking into account clinical and characteristic histological findings (flame figures). Although multiple potential triggers have been proposed, the exact etiology remains unresolved. Involvement of abnormal Th2 cells, IL‐5, and activated eosinophilic granulocytes suggest a nonspecific hypersensitivity response to exogenous or endogenous stimuli. Corticosteroids may have a beneficial effect on the chronic, recurrent course frequently observed. The disease is often self‐limiting, healing without sequelae. Given that transitions to hematological and oncological disorders have been observed, patients should be closely followed up.     

Wells syndrome

Wells syndrome, or eosinophilic cellulitis, is a rare disorder characterized by erythematous plaques evolving into dermal or subcutaneous masses. The histopathology shows degenerative collagen, histiocytes, and eosinophils. Although most cases of Wells syndrome occur in adults, we present a child with these clinical and histopathologic findings.     

Congenital Wells Syndrome

Abstract: We describe a girl with eosinophilic cellulitis (Wells syndrome) in whom the disease appeared immediately after birth with subcutaneous nodules on t he scalp and trunk, followed by the characteristic skin swelling and erythema at the age of 6 months. The lesions disappeared after a few weeks, but recurred several times. The mother had consumed large quantities of medications during the pregnancy, including iron, vitamins, and "natural remedies." Based on time of onset, this may be regarded as a unique case of congenital Wells syndrome. Its relation to the medications taken by the mother remains speculative. Subcutaneous nodules may be the presenting sign of Wells syndrome in children.     

Muckle–Wells Syndrome: A Case Report with an NLRP3 T348M Mutation

Autoinflammatory syndromes are a recently described group of conditions caused by mutations in multiple genes that code for proteins of the innate immune system. Cryopyrin‐associated periodic syndromes are autoinflammatory diseases comprising three clinically overlapping disorders: familial cold urticaria syndrome, Muckle–Wells syndrome (MWS), and neonatal‐onset multisystem inflammatory disease. MWS is characterized by a moderate phenotype with fever, rash, arthralgia, conjunctivitis, sensorineural deafness, and potentially life‐threatening amyloidosis. We report a 5‐year‐old girl with MWS that manifested as a recurrent skin rash without fever episodes or intracranial hypertension with papilledema. Genetic analysis revealed a T348M mutation of the NLRPR 3 gene in the patient and her mother. She was successfully treated with the interleukin‐1β antagonist receptor anakinra.