The First Report on Clinical Manifestation of Cryopyrin-Associated Periodic Syndrome in Korean Children

PURPOSE: The aim of this study was to evaluate the clinical characteristics of children diagnosed as cryopyrin-associated periodic syndrome (CAPS) in Korea. METHODS: Diagnosis was made based on clinical features and confirmed by a mutation in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene. Especially, osteocartilaginous overgrowth in the patella or distal femur was so characteristic that its presence warranted a diagnosis of chronic infantile neurologic cutaneous and articular/NOMID. RESULTS: We observed the clinical features of 9 Korean CAPS patients. All the patients suffered from an urticarial rash with recurrent fever. Among the 9 patients, 6 presented with rash and 4 with fever on the 1st or 2nd days of birth. Eight patients showed myalgia, and 7 patients showed arthralgia in the joints, and 6 patients showed radiologic findings of arthropathy including cupping of the metaphysis, excessive growth of the epiphysis, osteopenia or overgrowth of the cartilage. Four patients showed brain atrophy, enlarged ventricles or leptomeningeal enhancement on magnetic resonance imaging. Intellectual disability was observed in 1 patient. Five patients had eye involvement as conjunctivitis, uveitis, chorioretinitis, avascular area or papillary edema, and 3 patients showed progressive hearing loss. All 9 patients showed increased C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). CONCLUSIONS: All the patients carried a mutation on exon 3 of the CIAS1 gene. After the anakinra (interleukin-1 receptor antagonist) therapy, the fever and rash immediately disappeared, and CRP and ESR were improved.

Wells' Syndrome Associated with Molluscum Contagiosum in a Child: A Case Report / 대한피부과학회지

Wells' syndrome or eosinophilic cellulitis is usually observed in adults who present with pruritic, erythematous and edematous plaques associated with papules or vesicles. It is a rare inflammatory dermatosis of unknown etiology showing an eosinophil-mediated immune response. Classical histopathological features observed in patients are eosinophil-predominant inflammatory infiltration and marked dermal edema, along with ‘flame figures’. An 11-year-old boy presented with edematous plaques surmounted by vesicles on his abdomen and lower extremities. A month prior to presentation, these skin lesions occurred on other parts of his abdomen; however, they resolved spontaneously within a week. Skin biopsies from the recurrent lesions showed features consistent with Wells' syndrome and a few molluscum bodies in the epidermis. Laboratory tests showed peripheral eosinophilia. We concluded that Wells' syndrome in this young patient was caused by preceding molluscum contagiosum infection.

A Case of Ankyloblepharon-Ectodermal Defect-Cleft Lip and/or Palate (AEC) Syndrome with Missense Mutation in TP63 1657(th)

Ankyloblepharon-ectodermal defects-cleft lip and/or palate (AEC) syndrome, also known as Hay-Wells syndrome, is a rare autosomal dominant disorder characterized by congenital ectodermal dysplasia. It is caused by mutations in p63 gene. Six isoforms are generated from the TP63 gene mutation and the main isoform expressed in postnatal skin is Np63a, which functions as a key regulator of epidermal integrity. We have experienced a 1-day-old female baby with skin erosions, ankyloblepharosis, and cleft palate that require treatment for skin care and feeding difficulties. Missense mutation in TP63 1657(th) T → A transition was found in the genetic test performed in the patient, and this genotype has not been reported in a previously variant. The patient was found dead at 91days of birth and the cause of death was estimated by aspiration.

Diretrizes de conduta e tratamento de síndromes febris periódicas associadas à criopirina (criopirinopatias – CAPS) / Guidelines for the management and treatment of periodic fever syndromes

Resumo Objetivo: Estabelecer diretrizes baseadas em evidências científicas para manejo das síndromes periódicas associadas à criopirina (criopirinopatias – Caps). Descrição do método de coleta de evidência: A diretriz foi elaborada a partir de quatro questões clínicas que foram estruturadas por meio do PICO (Paciente, Intervenção ou Indicador, Comparação e Outcome), com busca nas principais bases primárias de informação científica. Após definir os estudos potenciais para sustento das recomendações, esses foram graduados pela força da evidência e pelo grau de recomendação. Resultado: Foram recuperados, e avaliados pelo título e resumo, 1.215 artigos e selecionados 42 trabalhos para sustentar as recomendações. Recomendações: 1. O diagnóstico de Caps é baseado na anamnese e nas manifestações clínicas e posteriormente confirmado por estudo genético. Pode se manifestar sob três fenótipos: FCAS (forma leve), MWS (forma intermediária) e Cinca (forma grave). Avaliações neurológica, oftalmológica, otorrinolaringológica e radiológica podem ser de grande valia na distinção entre as síndromes; 2. O diagnóstico genético com análise do gene NLRP3 deve ser conduzido nos casos suspeitos de Caps, isto é, indivíduos que apresentam, antes dos 20 anos, episódios recorrentes de inflamação expressa por urticária e febre moderada; 3. As alterações laboratoriais incluem leucocitose e elevação nos níveis séricos de proteínas inflamatórias; 4. Terapias alvo dirigidas contra a interleucina 1 levam a rápida remissão dos sintomas na maioria dos pacientes. Contudo, existem limitações importantes em relação à segurança em longo prazo. Nenhuma das três medicações anti-IL1β evita progressão das lesões ósseas.

Abstract Objective: To establish guidelines based on cientific evidences for the management of cryopyrin associated periodic syndromes. Description of the evidence collection method: The Guideline was prepared from 4 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. Results: 1215 articles were retrieved and evaluated by title and abstract; from these, 42 articles were selected to support the recommendations. Recommendations: 1. The diagnosis of CAPS is based on clinical history and clinical manifestations, and later confirmed by genetic study. CAPS may manifest itself in three phenotypes: FCAS (mild form), MWS (intermediate form) and CINCA (severe form). Neurological, ophthalmic, otorhinolaryngological and radiological assessments may be highly valuable in distinguishing between syndromes; 2. The genetic diagnosis with NLRP3 gene analysis must be conducted in suspected cases of CAPS, i.e., individuals presenting before 20 years of age, recurrent episodes of inflammation expressed by a mild fever and urticaria; 3. Laboratory abnormalities include leukocytosis and elevated serum levels of inflammatory proteins; and 4. Targeted therapies directed against interleukin-1 lead to rapid remission of symptoms in most patients. However, there are important limitations on the long-term safety. None of the three anti-IL-1β inhibitors prevents progression of bone lesions.

A Case of Eosinophilic Cellulitis in a Child / 대한피부과학회지

No abstract available.

Síndrome de Wells: uma dermatose reacional / Wells syndrome: a reactional dermatosis

A Síndrome de Wells é uma desordem cutânea rara, caracterizada clinicamente por placas enduradas semelhantes à celulite. Sua patogênese é desconhecida, mas a possibilidade de hipersensibilidade local foi proposta. Relatamos um caso de uma paciente de seis anos, que apresentava placas eritêmato-edematosas em membros inferiores, cuja histopatologia evidenciou infiltrado inflamatório misto com inúmeros eosinófilos de permeio em meio à degeneração da trama colágena eosinofílica ("figuras em chama"). A única anormalidade nos exames laboratoriais foi eosinofi lia. Esta paciente apresentava hipersensibilidade à picada de insetos. Verificou-se boa resposta ao corticoide tópico. A Síndrome de Wells é um provável estado cutâneo reacional a diversos estímulos e, portanto, cabe a investigação necessária. Na presente paciente, a picada de insetos parece ter sido o fator desencadeante

Wells syndrome is a rare skin disorder clinically characterized by hardened plaques similar to cellulite. Its pathogenesis is unknown, but the possibility of local hypersensitivity has been proposed. We report the case of a six-year-old who presented with erythematous and edematous lower limbs, whose histopathology showed a mixed inflammatory infiltrate with numerous intermingled eosinophils amid eosinophilic collagen degeneration ("flame figures"). The only abnormality in laboratory tests was eosinophilia. This patient had hypersensitivity to insect bites. There was good response to topical steroids. Wells syndrome is a likely cutaneous condition in reaction to various stimuli, and therefore the necessary investigation should be made. In this patient, insects' sting seems to have been the triggering factor

Wells syndrome: a clinical and histopathological review of seven cases / 中华皮肤科杂志

Objective To assess the clinical and histopathological features as well as treatment of Wells syndrome.Methods The clinical and pathological findings from 7 patients with Wells syndrome were retrospectively reviewed.Results Lesions were located on both lower extremities in 4 patients,on the back in 1 patient,on the face and trunk in 1 patient,and on the buttocks in 1 patient.Clinical manifestations included cellulitis (n =3),urticaria (n =1 ),annular plaques (n =1 ) and papulonodules (n =2).Histopathological examination of skin biopsies showed an infiltrate of numerous eosinophils with occasional flame figures in the dermis of all the patients.Leucocytoclastic vasculitis was found in 3 cases.No triggering factors were found in any of the 7 cases.The lesions nearly subsided in 3 patients after 2-week treatment with oral small-dosage prednisone and tripterygium glycosides.Conclusions Wells syndrome shows a wide diversity of clinical manifestations with distinct histological features.Systemic glucocorticoids and tripterygium glycosides are effective for the control of this condition.

AEC Syndrome Confirmed by Genetic Study in Neonate: A Case Report / 대한주산의학회잡지

AEC syndrome (Ankyloblepharon-Ectodermal defects-Cleft lip/palate syndrome) is a rare disorder characterized by ankyloblepharon, ectodermal dysplasia and cleft lip or palate. This disease is inherited in an autosomal dominant pattern with variable expressivity, and mutations in the TP63 gene on chromosome 3q28 are the genetic basis. A 14-day-old Korean boy presented with coarse, sparse hair on his scalp, erosive dermatitis, nail dysplasia, and a cleft palate at birth. Direct sequence analysis of the entire coding region of the TP63 gene of this boy showed a missense mutation c.1739 C>T (p.Ser541Phe) in the sterile-alpha-motif (SAM) domain. Family study revealed that neither of the parents had the mutation, indicating the de novo occurrence of the mutation. This is the second Korean case report of a genetically confirmed as AEC syndrome.

Wells' Syndrome Associated with Churg-Strauss Syndrome

Churg-Strauss syndrome (CSS) is a multisystem granulomatous vasculitis that is characterized by peripheral eosinophilia and the infiltration of eosinophils into systemic organs. The skin lesions of CSS consist mainly of palpable purpura and nodules. Wells' syndrome (WS) is a rare inflammatory dermatosis that is associated with recurrent granulomatous dermatitis and eosinophilia. Since these two diseases are rare, any overlap between them is very unusual. Herein, we report a patient with CSS, who initially presented a skin eruption of erythematous urticarial-plaques, vesicles, and blisters. Upon biopsy, the histology of these plaques indicated eosinophilic infiltration and "flame figures" within the dermis, which was consistent with a diagnosis of WS. Although the association between WS and CSS that was observed in our patient may be purely coincidental, it could also suggest a common pathogenetic background of these two distinct diseases, as both share several many common features.

One Case of Wells' Syndrome Successfully Treated with Kampo Medicines / 日本東洋医学雑誌

Wells' syndrome (eosinophilic cellulitis), whose etiology is idiopathic, is clinically characterized by solitary or multiple cellulitis-like eruptions which occur on the extremities and trunk. Corticosteroids are usually used for palliative treatment, but relapses are often observed. We observed an 8 year-old patient with Wells' syndrome successfully treated with Kampo medicines. In 2001, skin eruptions appeared on his extremities. In 2002, a histopathologic examination determined his disease to be Wells' syndrome, and corticosteroids were subsequently used for treatment. In January 2007, his skin eruptions worsened, and he first visited our outpatient clinic in May. After oral administration with keigairengyoto, his skin eruptions were slightly improved, but afterwards, they again worsened. In June, jumihaidokuto was administered instead of the former prescription, and the skin conditions had begun to improve. Because dry skin appeared in November, keigairengyoto was again added. With these treatments, his skin eruptions stably improved. In previous reports, Kampo medicines had not been used for the treatment of Wells' syndrome. This case, however, suggests that Kampo medicines are a candidate for the treatment of Wells' syndrome.

A Case of Bullous Eosinophilic Cellulitis / 대한피부과학회지

Eosinophilic cellulitis is a rare recurrent inflammatory dermatosis, characterized clinically by well-circumscribed erythematous plaques. The histopathologic features of the lesions are dermal edema, infiltration of eosinophils and development of 'flame figures' in the dermis. A 64-year-old female presented pruritic erythematous plaques, with associated bullae, on her right hand and wrist. Histopathologic examination showed infiltration of eosinophils and characteristic flame figures in the dermis. The clinical presentation and histopathologic alterations are consistent with the diagnosis of eosinophilic cellulitis. Herein, we report a case of bullous eosinophilic cellulitis which is an uncommon variant of eosinophilc cellulitis.

Bullous Eosinophilic Cellulitis (Wells' Syndrome) in a Patient with Churg-Strauss Syndrome: A Case Report and Review of Literatures / 대한류마티스학회지

Wells' syndrome is an inflammatory dermatosis with associated aberrant eosinophil responses caused by unknown factors. Its histology is characterized by erythematous plaques with "flame figures" in the dermis, which is potentially diagnostic but not pathognomic. Cases of Wells' syndrome in patients with Churg-Strauss syndrome (CSS), which is characterized by antineutrophil cytoplasmic antibody-related necrotizing vasculitis, marked peripheral eosinophilia, and eosinophil tissue infiltrates, have rarely been reported, and the pathogenic association between these two diseases remains undetermined. Differences of clinical and histopathologic features of these two diseases suggest that they are distinct disease entities, even though, in part, they share pathogenic mechanisms. Here we present a new case with Wells' syndrome in a patient with CSS, treated with systemic steroid.

Three Cases of Wells' Syndrome / 대한피부과학회지

Wells' syndrome was first described by Wells in 1971 as a recurrent granulomatous dermatitis with eosinophilia and was later named eosinophilic cellulitis. It is defined by the following criteria: sudden onset of annular or circinate erythematous-edematous patches that rapidly evolve to morphea-like blue-slate-colored plaques; a histological feature characterized usually by the presence of 'flame figures'; non-constant blood hypereosinophilia. We present clinical and histopathologic features of three cases of eosinophilic cellulitis.

Wells' Syndrome Associated with Esophageal Squamous Cell Carcinoma / 대한피부과학회지

Wells' syndrome or eosinophilic cellulitis is a recurrent inflammatory dermatosis, characterized clinically by acute dermatitis resembling cellulitis. The histopathologic findings show diffuse dermal eosinophilic infiltration and characteristic `flame figures'. The etiology and pathogenesis are unknown, however, various associated disorders such as hematological diseases, infections, arthropod bites, drugs, and surgery have been documented. Wells' syndrome has previously been reported in only 4 cases of non-hematological malignancy. A 57-year-old man with esophageal squamous cell carcinoma developed recurrent, mildly tender, urticarial plaques on the trunk and left forearm. A skin biopsy specimen revealed histopathologic findings compatible to Wells' syndrome. Skin lesions resolved with systemic corticosteroids therapy without recurrence until now. We report a case of Wells' syndrome associated with esophageal squamous cell carcinoma

A Case of Wells' syndrome / 대한피부과학회지

Wells' syndrome, also called eosinophilic cellulitis, is characterized by recurrent cutaneous swellings, which resemble acute bacterial cellulitis, distinctive histopathological changes, dermal eosinophilic infiltration and characteristic flame figure. A 53-year-old woman developed pruritic, erythematous, and edematous plaques on chest, abdomen, back and both upper arms. Histology of the plaques revealed a diffuse infiltration of eosinophils and flame figure in the dermis without granulomatous and vasculitic process, consistent with the diagnosis of Wells' syndrome.

A Case of Wells' Syndrome in a Child / 대한피부과학회지

Wells' syndrome, or eosinophilic cellulitis, is characterized clinically by an acute dermatitis resembling cellulitis, which evolves into violaceous plaques that resolve spontaneously without scarring. The histopathologic features show dermal eosinophil infiltration and development of characteristic `flame figure'. Wells' syndrome has been described mainly in adults, and less than 20 childhood cases have been reported. We herein report a case of Wells' syndrome in a 3-year-old boy.

A Case of Wells' Syndrome Treated with Systemic PUVA / 대한피부과학회지

Wells' syndrome, or eosinophilic cellulitis, is characterized by recurrent cutaneous swellings which resemble acute bacterial cellulitis, and by distinctive histopathological changes. Skin lesions show dermal eosinophilic infiltration and the characteristic 'flame figures', but not pathognomonic, which are composed of eosinophil major protein deposited on collagen bundles. A 51-year-old woman developed a chronic, pruritic, erythematous to dark-brown colored, annular, infiltrated plaques with papules, vesicles and some crusts on the chest, abdomen, back and both forearms with the clinical and histological features of Wells' syndrome. Skin lesions had recurred frequently with systemic corticosteroids therapy, so we tried systemic PUVA and treated her successfully without recurrence until now.

A Case of Wells' Syndrome Treated with Systemic PUVA / 대한피부과학회지

Wells' syndrome, or eosinophilic cellulitis, is characterized by recurrent cutaneous swellings which resemble acute bacterial cellulitis, and by distinctive histopathological changes. Skin lesions show dermal eosinophilic infiltration and the characteristic 'flame figures', but not pathognomonic, which are composed of eosinophil major protein deposited on collagen bundles. A 51-year-old woman developed a chronic, pruritic, erythematous to dark-brown colored, annular, infiltrated plaques with papules, vesicles and some crusts on the chest, abdomen, back and both forearms with the clinical and histological features of Wells' syndrome. Skin lesions had recurred frequently with systemic corticosteroids therapy, so we tried systemic PUVA and treated her successfully without recurrence until now.

A Case of Wells' Syndrome Associated with Pancreatic Carcinoma / 대한피부과학회지

Wells' syndrome or eosinophilic cellulitis is an uncommon cutaneous disorder characterized by recurrent erythematous and edematous plaques that often resemble acute cellulitis. The characteristic microscopic findings are diffuse dermal eosinophilia with marked edema, and flame figures consisting of amorphous or granular eosinophilic material around collagen bundles of the dermis. Etiology and pathogenesis are unknown, but the disease has been found to be associated with infections, arthropod bites, drug administration, surgery and hematologic disorders. We report the case of a 55-year-old man with pancreatic carcinoma who was presented with an asymptomatic erythematous to brownish subcutaneous nodule on the left buttock of several days' duration. A biopsy specimen taken from the erythematous to brownish nodule showed many flame figures and diffuse infiltration of eosinophils in the dermis and subcutaneous fat tissue. The rapid resolution of the skin lesion with chemotherapy of the pancreatic carcinoma supports a relationship between the two conditions.

Eosinophilic Cellulitis (Wells' Syndrome)

Eosinophilic cellulitis is a rare dermatosis first described by Wells, and characterized by recurrent episodes of sudden outbreaks of erythematous cutaneous swellings often painful or pruritic. Microscopically, the lesion shows diffuse tissue eosinophilia and fibrinoid flame figures, evolution of associated focal necrobiosis, and formation of focal microgranulomas associated with eosinophils. The cause is still unknown but the triggers which have been thought to precipitate the disease include insect bites, parasitic infections such as toxocara, onchocerciasis, nasopharyngeal carcinoma, rheumatoid arthritis and spider bites. However many cases are idiopathic. The author experienced a case of eosinophilic cellulitis of a 52-year-old woman with multiple cutaneous tender plaques of cellulitis for approximately 10 years with history of repeated remission and recurrent episodes. Biopsy was taken from ulcerated edematous nodule of inguinal region under the clinical impression of deep fungal infection, pyoderma gangrenosum and polyarteritis nodosa. Cultures for fungal and common organisms were negative. Histologically, the entire dermis was infiltrated by numerous eosinophils and scattered histiocytes. There were scattered flame figures showing necrobiotic foci in the collagen with accumulation of eosinophils, granulated free cosinophilic granules and histiocytes.