Severe Erythroderma Research Articles

A Case of Severe Erythroderma in a Patient with Pustular Psoriasis

Case Presentation: A patient with a known history of pustular psoriasis presented with sub-acute development of diffuse erythema and scaling of the skin with areas of exfoliation consistent with erythroderma. She was ill appearing and required admission and aggressive treatment with steroid-impregnated wet dressings, topical emollients, analgesics and systemic immunosuppressants. Discussion: Erythroderma is a dermatologic emergency characterized by diffuse erythema and scaling spanning >90% of skin surfaces and is associated with a mortality rate as high as 64%. It is initially a clinical diagnosis and needs to be recognized and aggressively treated expeditiously to improve chances of a good outcome.

Erythrodermic Atopic Dermatitis Associated with Dust Mite and Alternaria alternata in an Eight-Year-Old Child: A Case Report

Atopic Dermatitis (AD) is a chronic inflammatory condition of the skin characterised by itching, recurrent lesions, and lichenification. Erythroderma also known as generalised exfoliative dermatitis, is characterised by erythema that covers more than 90% of the body’s surface. These erythematic lesions are much more prone to infection. In present case, an eight-year-old girl presented with a chief complaint of rashes all over the body with severe itching from two years presented to the Allergy and Asthma Centre. She had positive history of atopy and multiple septicaemia-related hospitalisations since last two years. Skin biopsy leads the diagnosis of Spongiotic Dermatitis consistent with Erythroderma secondary to AD. Multiple allergies, including those to dust mites (DP der p2, p21, DF der f2) and Alternaria alternata (alt 1), were identified by Component-Resolved Diagnosis (CRD). Cyclosporin’s, Omalizumab (a monoclonal antibody against immunoglobulin E), and allergen-specific sublingual immunotherapy were given for the management and all gave excellent results in the patient. AD can be properly diagnosed and treated in its early stages, breaking the cycle that leads to severe erythroderma. To fully comprehend the molecular and immunological genesis of these allergic types, more research is required.

TMEM244 Gene Expression as a Potential Blood Diagnostic Marker Distinguishing Sézary Syndrome from Mycosis Fungoides and Benign Erythroderma

Sézary syndrome (SS) is a rare, aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL). The disease is characterized by severe erythroderma, generalized lymphadenopathy, and the presence of circulating Sézary cells that are a clonal proliferation of CD4+/CD45RO+ malignant T lymphocytes primarily involving the skin (Huet et al., 2006; Willemze et al., 2005). SS is a leukemic variant of CTCL and is closely related to mycosis fungoides (MF), a more indolent and slowly progressing type (Booken et al., 2008).

Meta-Analysis of Mutations in ALOX12B or ALOXE3 Identified in a Large Cohort of 224 Patients.

The autosomal recessive congenital ichthyoses (ARCI) are a nonsyndromic group of cornification disorders that includes lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. To date mutations in ten genes have been identified to cause ARCI: TGM1, ALOX12B, ALOXE3, NIPAL4, CYP4F22, ABCA12, PNPLA1, CERS3, SDR9C7, and SULT2B1. The main focus of this report is the mutational spectrum of the genes ALOX12B and ALOXE3, which encode the epidermal lipoxygenases arachidonate 12-lipoxygenase, i.e., 12R type (12R-LOX), and the epidermis-type lipoxygenase-3 (eLOX3), respectively. Deficiency of 12R-LOX and eLOX3 disrupts the epidermal barrier function and leads to an abnormal epidermal differentiation. The type and the position of the mutations may influence the ARCI phenotype; most patients present with a mild erythrodermic ichthyosis, and only few individuals show severe erythroderma. To date, 88 pathogenic mutations in ALOX12B and 27 pathogenic mutations in ALOXE3 have been reported in the literature. Here, we presented a large cohort of 224 genetically characterized ARCI patients who carried mutations in these genes. We added 74 novel mutations in ALOX12B and 25 novel mutations in ALOXE3. We investigated the spectrum of mutations in ALOX12B and ALOXE3 in our cohort and additionally in the published mutations, the distribution of these mutations within the gene and gene domains, and potential hotspots and recurrent mutations.

Generalized Pustular Psoriasis of Von Zumbusch in a Balinese Elderly: A Rare Case Report

Generalized pustular psoriasis (GPP) of von Zumbusch is a unique and rare type of psoriasis. The severe inflammatory skin disease has been postulated of having its relation to immunogenetics and exacerbated by various factors. Most GPP cases are sporadic, characterized by cutaneous manifestations of severe erythroderma, scaling skin, the lake of pustules, and may be accompanied by extracutaneous manifestations, including acute respiratory distress syndrome, heart failure, and sepsis. This investigation reported GPP in an elderly man with prior untreated psoriasis vulgaris and pneumonia, which, to our knowledge, was the first case in our secondary regential hospital, Bangli Medika Canti Hospital. The patient underwent systemic and topical corticosteroid therapy, intravenous ceftriaxone, wound dressing, and moisturizer, which yielded a satisfactory result. We present a case and literature review of this distinct phenomenon.

Omenn syndrome- A rare immunodeficiency disorder: A case report

Introduction: Omenn syndrome, a variant of severe combined immunodeficiency disorder, is a rare condition, with few cases reported in literature. Case Characteristics: A three month old female infant presented with recurrent severe infections, chronic diarrhea, severe erythroderma and lymphadenopathy. Immunological work-up revealed agammaglobulinemia, with both B cell and T cell deficiency. Genetic studies were compatible with Omenn syndrome. Outcome: Bone marrow transplantation was planned, but the infant succumbed to complications. Message: In a young infant with recurrent severe infections, characteristic skin lesions and combined immunodeficiency, Omenn syndrome should be suspected. Keywords: Immunodeficiency, Omenn syndrome, Early diagnosis.

LB954 Value of topical hypochlorite and skin acidification in improving severe erythroderma of Omenn syndrome

LB954 Value of topical hypochlorite and skin acidification in improving severe erythroderma of Omenn syndrome

Molecular Characteristics, Clinical and Immunologic Manifestations of 11 Children with Omenn Syndrome in East Slavs (Russia, Belarus, Ukraine).

Omenn syndrome [Mendelian Inheritance (OMIM 603554)] is a genetic disease of the immune system, characterized by the presence of fatal generalized severe erythroderma, lymphoadenopathy, eosinophilia and profound immunodeficiency. We studied clinical and immunologic presentation of the disease manifestation among East Slavs population with genetically confirmed Omenn syndrome. We collected clinical and immunologic data of 11 patients (1 from Belarus, 5--Ukraine, 5--Russia): 6 females, 5 males. The age of Omenn syndrome manifestation varied from the 1st day of life to 1 year and 1 month, the age of diagnosis--20 days to 1 year and 10 months. Nine out of 11 patients had classic immunologic phenotype T(+/-)B-NK+, 1 pt had TlowB + NK+ with CD3 + TCRgd + expansion and 1 had TlowB+/-NK+ phenotype. Eight out of 11 pts had mutation in RAG1 gene, 4 out of 8 had c.368-369delAA (p.K86fsX118) in homozygous state or heterozygous compound. In our cohort of patients, we also described two new mutations in RAG genes (p.E722Q in RAG1 and p.M459R in RAG2). At present, 7/11 were transplanted and 5 out of the transplanted are alive. This study demonstrates that the most popular genetic abnormality in East Slavs children with Omenn syndrome is c.368-369delAA (p.K86fs118) in RAG1 gene, which may be connected with more favorable prognosis because 4/4 patients survived after hematopoietic stem cells transplantation.

Recent advances in congenital ichthyoses.

In 2010, a new classification of the congenital ichthyoses was published. At the time, the causative genes were known in many but not all instances. The goal of this review is to provide an update on molecular and clinical findings in congenital ichthyosis and to revise evidence-based and emerging treatments. Mutations in genes encoding for desmosomal components have recently been shown to cause three clinically overlapping entities: peeling skin disease; severe dermatitis, multiple allergies and metabolic wasting syndrome; and Netherton syndrome. Mutations in keratin 10 have been identified as the cause of ichthyosis with confetti, a rare form of ichthyosis characterized by severe erythroderma in which healthy spots gradually develop since childhood. There is no curative treatment for the congenital ichthyoses. A recent systematic review of randomized clinical trials of ichthyosis treatments revealed that research evidence of therapy is poor. The expanding phenotype and genotype of the ichthyoses facilitates accurate clinical diagnosis and permits a deeper knowledge of the epidermal pathophysiology. Although curative treatment is yet to come, N-acetylcysteine has recently been added to the therapeutic armamentarium and topical enzyme replacement therapy has emerged as a promising alternative in TG1-deficient individuals.

A Suspected Case of Silodosin-Induced Erythroderma.

An 86-year-old man developed a suspected severe erythroderma during treatment with silodosin (dosage unknown) for benign prostatic enlargement. Two weeks after starting silodosin, he developed a total-body scaling dermatitis. A biopsy was planned but the patient improved at his subsequent visit and it was not taken. Silodosin was discontinued and the patient received UVB phototherapy, clobetasol ointment, and several bland and protective skin-care measures. One week after the initial presentation, the patient demonstrated improvement in his total-body scaling. Based on these findings, the patient was diagnosed with a suspected silodosin-induced erythroderma. Due to limitations in the patient’s clinical history and investigations, a Naranjo assessment score was not obtainable.

Systemic lupus erythematosus presenting as erythroderma

Introduction: systemic lupus erythematosus (sLE) is an autoimmune disorder involving multiple organs, predominantly seen in women of child-bearing age. Erythroderma is described in patients with subacute cutaneous lupus erythematosus (scLE) but is rare in sLE. Among the cardiac manifestations, pericarditis is common but myocarditis is rare. We report a case of severe sLE presenting with erythroderma, pancytopenia, arthralgia and myocarditis. case report: A 67-year-old male with a background history of hypertension, transient ischemic attack and polymyalgia rheumatica presented with severe erythroderma, malaise, arthralgia, weight loss and was found to be pancytopenic. His antinuclear antibody (ANA) was positive and double stranded DNA (dsDNA) was more than 200 IU/mL with very low complement levels. He developed lupus associated myocarditis with moderately impaired global left ventricular systolic function. He was initially started on steroids and hydroxychloroquine. but as he

Epoprostenol: Flushing or Erythroderma?

Dear Editor: Epoprostenol is a synthetic prostacycline that remains the first line treatment for patients with severe pulmonary hypertension (PH)1-3. Herein, we present a case of severe erythroderma associated with the initiation of therapy with intravenous epoprostenol. A 50-year-old woman with PH secondary to CREST syndrome (Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly, Telangiectasia), gastroesophageal reflux disease, and chronic obstructive pulmonary disease treated with acenocoumarol, furosemide, spironolactone, tiotropium inhaled, budesonide/formoterol inhaled, azathioprine, omeprazole and oxygen for the 5 years prior presented to our clinic. Because of the severity of her symptoms secondary to PH, 12 ng/kg/min IV epoprostenol was prescribed for treatment. During the first month, the patient's dyspnea improved and a discrete asymptomatic erythema appeared. One month later, we increased the patient's epoprostenol dose to 14 ng/kg/min. After 2 weeks, the patient developed a progressive maculopapular exanthema, chills, and intense pruritus, rapidly evolving to erythroderma with large areas of exfoliation (Fig. 1). The patient had no mucosal lesions, systemic symptoms, or fever. Haemograma and biochemical determinations were normal. Histopathologic examination of the skin was consistent with a true drug reaction, excluding just vasodilatation (Fig. 2). Epoprostenol was believed to be the most likely cause as it was the most recently added drug. Due to the severity of respiratory symptoms, epoprostenol was maintained and oral prednisone was initiated at 16 mg/24 h together with methylprednisolone 0.1% ointment. Fig. 1 Severe erythroderma associated with intravenous epoprostenol therapy. The patient presented her skin diffusely erythematous with accentuation on the extremities with large areas of exfoliation. Fig. 2 Epidermis with focal parakeratosis and superficial perivascular mononuclear infiltrate with occasional exocytosis of lymphocytes associated with spongiosis and eosinophils (HE A: ×10, B: ×40). One month later, the patient continued with diffuse erythema and intense pruritus, so epoprostenol was tapered to 12 ng/kg/min. One week later the patient's erythema improved, but her dyspnea increased, so epoprostenol was again increased to 14 ng/kg/min. The patient remained hemodynamically stable and her clinical cutaneous reaction slowly improved. Oral prednisone was tapered and epoprostenol was increased to 16 ng/kg/min. Two years later, the patient was tolerating epoprostenol with complete resolution of the erythroderma, without any change in her usual medication. Dose-limiting side effects of epoprostenol are related to prostenoid vasoactivity, such as flushing, jaw pain, arthralgia, myalgia, nausea, hypotension, and headache1,3,4. Patients receiving chronic epoprostenol therapy often develop slight erythema without other systemic symptoms4,5. Myers et al.4 reported cutaneous findings in patients receiving long-term epoprostenol therapy, including diffuse erythema with lower extremity accentuation, palpable purpura, brawny pretibial discoloration with edema, and one case of diffuse erythroderma and exfoliation4,5. In this case, they described a woman with PH secondary to connective tissue disease and who developed severe erythroderma that improved after discontinuation from drug treatment. Our patient had been following a stable medical regimen prior to receiving the new drug and she did not improve until the dose of epoprostenol was tapered; however, the drug was not discontinued. Our patient developed an erythroderma with at the dose of 14 ng/kg/min, slightly higher than a case published previously (11.5 ng/kg/min)4,5. The altered immune function associated with connective disease might increase the risk of drug-induced reaction5 independentof drug dose. Our patient clinical course indicates that it may not be necessary to stop epoprostenol therapy for resolution of severe toxicoderma. Inmunomodulatory effects of epoprostenol therapy are poorly understood at present. As far as we know, this is the second case published on severe toxic erythroderma caused by epoprostenol.

Atypical Cutaneous Lymphoproliferative Disorder: A Fatal Mimic of Cutaneous T-Cell Lymphoma in a Patient with HIV Infection

Atypical cutaneous lymphoproliferative disorder (ACLD) is a rare condition that has been associated with HIV infection. Patients with ACLD present with diffuse, erythematous and pruritic skin lesions accompanied by generalized lymphadenopathy. The clinical characteristics of ACLD overlap most notably with several other conditions including Mycosis Fungoides/Sézary Syndrome (MF/SS), a cutaneous lymphoma of T-cell lineage. Unlike Mycosis Fungoides, the noxious infiltrates of ACLD are not monoclonal but polyclonal and consist of cytotoxic CD8+ T-cells instead of CD4+ T-cells or B-cells. Highly active antiretroviral therapy (HAART) has been reported to improve ACLD. We describe the case of a Caucasian man with longstanding HIV infection who presented with severe erythroderma. Skin and lymph node biopsies showed polyclonal CD8+ T-cell infiltrates. Gene rearrangement studies did not reveal an obvious clonal disorder. Hallmark peripheral blood findings consisting of a severe depletion of CD4+ T-lymphocytes and markedly elevated CD8+ cells provided an important diagnostic clue. Despite the purported benefits of HAART in ameliorating this disorder, erythroderma and extreme pruritus improved only after the patient began taking mycophenolate mofetil and hydroxyurea. Unfortunately, he succumbed to complications of methicillin-resistant Staphylococcus aureus septicemia. We alert readers to this rare HIV-associated condition which may mimic other benign and malignant skin conditions and briefly discuss diagnostic and therapeutic options.

Omenn syndrome does not live by V(D)J recombination alone

During the past decade, easy access to sequence analyses has allowed us to increase our understanding of the pathogenesis of severe combined immunodeficiencies. Here, we describe the expanding clinical and immunological spectrum associated with Omenn syndrome phenotype. In particular, we review the cellular and molecular mechanisms involved in the pathophysiology of 'classical' Omenn syndrome due to the recombination activating gene (RAG) defects and of a new subgroup of Omenn-like disorders. Different types of mutations are associated with the Omenn phenotype characterized by skin erythroderma, oligoclonal-activated T cells and elevated IgE in the absence of circulating B cells. Extensive studies conducted over the last few years have allowed the definition of the 'classical form' of Omenn syndrome due to hypomorphic defects in genes involved in V(D)J recombination, mainly RAG genes, and 'Omenn-like' features associated with mutations in genes involved in the maturation steps of lymphoid cells other than V(D)J recombination. Moreover, an increasing number of diseases other than those due to V(D)J recombination defects develop Omenn signs. Impaired but not abolished V(D)J recombination process leads to the generation of a few T cells which expand in the periphery, infiltrate target organs such as skin and gut, resulting in severe erythroderma and colitis, both typical signs of Omenn syndrome. Extensive molecular studies now demonstrate that genes other than V(D)J molecules have a role in the pathogenesis of this disease, supporting the evidence that 'Omenn' defines an inflammatory condition associated with various genetic defects.

Remission of Severe CD8+Cytotoxic T Cell Skin Infiltrative Disease in Human Immunodeficiency Virus–Infected Patients Receiving Highly Active Antiretroviral Therapy

A CD8 cutaneous lymphoinfiltrative disease has been described in human immunodeficiency virus (HIV)-infected patients presenting with a severe erythroderma. The true nature of this severe skin infiltrative disorder is still elusive. Although some clinical features of this syndrome have raised the hypothesis of its malignant nature in initial observations, several studies have provided stronger support to the hypothesis that it is a reactive pseudotumoral process. From 1995 through 2008, 8 HIV type 1 (HIV-1)-infected patients presenting with a chronic skin eruption, diagnosed as CD8 T cell infiltration of the skin, were studied. All patients showed diffuse infiltrated skin with superficial lymphadenopathy. A profound CD4(+) lymphocytopenia and eosinophilia were other major features. Histological and immunostaining analysis revealed a predominant dermal and epidermal infiltration by CD8(+) T cells belonging to the cytotoxic lineage, without evidence for a monoclonal status by polymerase chain reaction-based molecular analysis of lesional skin. A remission of skin symptoms occurred in all cases following highly active antiretroviral therapy, which paralleled the decrease of HIV-1 RNA load and the increase of CD4(+) peripheral blood absolute count. Altogether, these results emphasize the reactive, nonmalignant nature of this syndrome and strongly support the coupling between HIV-induced immune deficiency and uncontrolled CD8 activation.

Neonatal erythroderma

Neonatal erythroderma is a potentially life-threatening condition in neonates less than 1 month old. During the first month of life, erythroderma is generally a presentation of genodermatosis, primary immune deficiency, or, more exceptionally, severe psoriasis, metabolic disease or infection. Atopic erythroderma is observed later in life, usually after the age of 1 month. Rapid determination of the underlying cause is crucial for better management. However, the diagnosis is often a challenge for the clinician and is frequently delayed due to the nonspecific nature of the clinical signs. We summarize the different causes of neonatal erythrodermas and list their clinical, biological, histological, and sometimes genetic characteristics. Severe erythroderma, typified by early onset, skin induration, severe alopecia and failure to thrive, is immediately suggestive of immunodeficiency or Netherton syndrome. In such cases, an early skin biopsy may be particularly of use in allowing accurate differentiation between these two disorders. This review outlines the clinical and histological features of these disorders and suggests an approach to their differential diagnosis and management.

Efficacy and safety of treatment of patients suffering from severe forms of psoriasis

A comparative clinical, laboratory and ultrasonic assessment of the efficacy and safety of Infliximab (Remicade®) and cyclosporine A as well as photochemotherapy on the basis of Oxsoralen in 90 patients suffering from severe plaque psoriasis and psoriatic erythroderma at the progression stage. Clinical and ultrasonic assessment demonstrated that Infliximab (Remicade®) is a highly efficient drug for treatment of severe plaque psoriasis and psoriatic erythroderma providing an evident reduction in inflammatory changes both in the epidermis and dermis as well as normalizing epidermal keratinization processes. A long-term maintenance treatment with Infliximab positively modifies the course of severe psoriasis in patients and is quite safe. A course of treatment with cyclosporine A and general photochemotherapy is quite efficient under similar conditions but its action is short-term. After the completion of the above-mentioned therapy, patients develop dermatosis relapses of the same severity and extent during a year of follow-up. According to the ultrasonic examination results, a course of treatment with cyclosporine A and photochemotherapy has a partial effect on pathohistology processes in psoriatic patients as well as entails a number of adverse effects.

Omenn syndrome: Inflammation in leaky severe combined immunodeficiency

Omenn syndrome (OS) was reported until recently as a distinct form (phenotype and genotype) of severe combined immunodeficiency (SCID). Similar to other patients with SCID, patients with OS present early in infancy with viral or fungal pneumonitis, chronic diarrhea, and failure to thrive. Unlike typical SCID, patients with OS have enlarged lymphoid tissue, severe erythroderma, increased IgE levels, and eosinophilia. The inflammation observed in these patients is believed to be triggered by clonally expanded T cells, which are predominantly of the T(H)2 type. These abnormal T cells, in the absence of proper regulation by other components of the immune system, secrete a host of cytokines that promote autoimmune as well as allergic inflammation. The emergence of these T-cell clones occurs in patients with hypomorphic mutations in recombination activating gene 1 or 2, but not in patients with deleterious mutations in these enzymes which render them inactive. Recently, OS was also identified in a growing list of other leaky SCIDs with mutations in RNA component of mitochondrial RNA processing endoribonuclease, adenosine deaminase, IL-2 receptor gamma, IL-7 receptor alpha, ARTEMIS, and DNA ligase 4. This new information revealed OS is a distinct inflammatory process that can be associated with genetically diverse leaky SCIDS.

Eritrodermia exfoliativa y dermatitis infecciosa en un lactante infectado por el virus linfotrópico humano-I (HTLV-I)

We report a HTLV-I positive infant, whose infection was confirmed by polymerase chain reaction. The infant presented with an acute, severe, generalized eczema, exfoliation and severe erythroderma that yielded to an acute proteic malnutrition and frequent staphylococcal infections, unresponsive to treatment, since the second month of life. Immunodeficiencies from other origin and other causes of erythroderma were ruled out. The histopathology studies and clinical course yielded to the diagnosis of infective dermatitis associated to HTLV-I. A review of the literature is performed.

Phase III Study of Denileukin Diftitox (ONTAK®) To Evaluate Efficacy and Safety in CD25+ and CD25- Cutaneous T-Cell Lymphoma (CTCL) Patients.

Denileukin diftitox (ONTAK®) is a genetically engineered fusion protein composed of the enzymatically active domain of diphtheria toxin and the full length sequence of interleukin-2 (IL-2), designed to target malignancies expressing the IL-2 receptor. The drug is approved for the treatment of CTCL in patients expressing the CD-25 component of the IL-2 receptor. L4389-14 is a phase III study designed to further evaluate the efficacy and safety of denileukin diftitox (DD) in distinct subgroups of CTCL patients. The study met its accrual goal of 90 patients and included three subgroups of patients: 1) CD25 (+) patients that crossover from a placebo course of treatment in a companion study (L4389-11) and had progressed or failed to respond during an 8-course placebo treatment (N=34); 2) CD25 (−) patients (N=36) and 3) CD25 (+) patients that had previously been treated with DD, responded, and subsequently relapsed (retreatment group, N=22). Patients entered the study at stages Ia to III and received DD at a dose schedule of 18mcg/Kg/day by IV infusion once daily for 5 days every 3 weeks for up to 8 cycles. Efficacy of treatment was assessed based on tumor burden, lymph nodes, lymphocyte count, and patient status (PGA) at every cycle, beginning on cycle 2. A response assessment required confirmation in two subsequent cycles. Responses were evaluated by an independent Drug Evaluation Review Committee. Assessment of activity of DD across the 3 groups based on an analysis of the data is shown in the table below. Patient demographics were consistent across subgroups and representative of a general CTCL population. Disease status at baseline was Stage IIa or earlier 66% of patients and stage IIb or higher 34% of patients. About 46% of patients presented with mild to severe erythroderma. Adverse events were similar to those previously observed with ONTAK. Serious adverse events of ≥5% incidence were nausea (9%), vomiting (5%), capillary leak syndrome (5%), pyrexia (9%) and infections (10%). The results of this large phase III trial showed very consistent efficacy of denileukin diftitox across treatment-naïve CD25 (+) and CD25 (−) patients, as well as in patients undergoing retreatment with DD. Duration of response and progression free survival were also quite favorable across the different CTCL subgroups.Response AssessmentCD25 (+) Placebo CrossoverCD25 (−)CD25 (+) RetreatmentN =343622ORR (CR/CCR/PR)47.1%30.6%36.4%CR/CCR17.6%8.3%9.1%PR29.4%22.2%27.3%SD29.4%44.4%31.8%PD20.6%25.0%31.8%Duration of Response (days)820340274Progression Free Survival (days)870Not reached429