Erythema elevatum diutinum: a review of presentation and treatment

Erythema elevatum diutinum (EED) is a rare, chronic and treatable skin condition. It has many histological mimics and is often associated with a variety of underlying systemic diseases, when these are present the management and prognosis dictates the course of the EED. This review aims to highlight the differential diagnosis, clinical manifestations of EED and the possible underlying systemic disease. It is important for clinicians to be aware that EED may predate underlying conditions and the presence of lesions may indicate underlying disease activity. In some cases one may need ‘search’ for underlying disease. Treatment of these lesions is notoriously difficult. Dapsone is used as the mainstay of treatment, however other options exist. We have highlighted different treatment options and suggested a treatment algorithm. In some cases, treatment may need to be targeted at underlying disease.     

A Practical Approach to Cutaneous Sarcoidosis

Sarcoidosis is a chronic inflammatory disorder that has the potential to affect multiple organs, including the skin. Its cutaneous manifestations are varied and can provide clues to underlying systemic manifestations. Unfortunately, they also can be disfiguring. Therapy is usually directed at the organ system most severely affected, which often may help cutaneous disease. However, cutaneous disease may be recalcitrant to treatment directed at extracutaneous disease, or it may be severe enough to require targeted therapy. This article focuses on the dermatologist’s role in recognizing and diagnosing cutaneous sarcoidosis, evaluating patients for systemic disease involvement, and treating the skin manifestations of sarcoidosis.     

持久性隆起性红斑伴再生障碍性贫血一例并文献复习

持久性隆起性红斑(erythema elevatum diutinum, EED)是一种罕见的皮肤白细胞破碎性血管炎,其病因不明确,认为与感染、血液系统疾病、自身免疫性疾病感染的循环免疫复合物在血管壁沉积有关,因此除单纯的皮肤表现外,既往报道39.4%的EED伴发HIV、病毒性肝炎、链球菌感染、副蛋白血症、骨髓增生异常综合征、系统性红斑狼疮和类风湿性关节炎等疾病。现报道我院诊治的持久性隆起性红斑伴再生障碍性贫血一例,并通过文献检索,分析伴发其他系统性疾病的EED的临床特征,初步探讨EED与血液系统疾病及恶性肿瘤的关联性。     

The value of lymphocytopenia as a marker of systemic involvement in cutaneous lupus erythematosus

BACKGROUND: Some patients suffering from cutaneous lupus erythematosus (CLE) develop extracutaneous manifestations during the course of the disease: up to 5% of patients with discoid LE (DLE) and up to 30% of subacute cutaneous LE (SCLE) patients show systemic involvement. Recent studies revealed some markers indicating systemic manifestations of CLE patients. However, the significance of diminished peripheral lymphocyte numbers as a marker of systemic involvement in CLE has not been investigated before. OBJECTIVES: To determine the value of lymphocytopenia (< 1500 cells microL(-1)) as a marker of extracutaneous manifestations in CLE patients. : Methods The records of 72 CLE patients (44 DLE; 28 SCLE) were investigated. Systemic involvement was defined in accordance with the criteria of the European Academy of Dermatology and Venereology. Analyses of peripheral lymphocyte numbers were done by fluorescence-activated cell sorter analysis. RESULTS: Five CLE patients developed extracutaneous manifestations during the course of disease. All these patients were lymphocytopenic. Differences between peripheral lymphocyte numbers of CLE patients with and without additional systemic involvement were highly significant (P < 0.01). CONCLUSIONS: Our results suggest that lymphocytopenia in patients with CLE is a high sensitive but low specific marker of systemic involvement.     

Sarcoidosis: a comprehensive review and update for the dermatologist: part II. Extracutaneous disease

Sarcoidosis is a multisystemic, granulomatous disease with protean manifestations and variable prognosis. Because the skin can be the only organ in which the disease is recognized, dermatologists may be responsible for the care of sarcoidosis patients. Therefore, dermatologists should be cognizant of the disease's extracutaneous manifestations to assure appropriate evaluation and treatment. Part II of this review describes the diagnostic approach and management of the extracutaneous manifestations of sarcoidosis.     

Eruptive juvenile xanthogranuloma associated with relapsing acute lymphoblastic leukemia

Abstract:  Juvenile xanthogranuloma is a benign, self-healing disorder with characteristic lesions mainly involving the skin. Although most patients with juvenile xanthogranuloma have only cutaneous symptoms, recent articles have documented extracutaneous manifestations: systemic involvement of many organs has been reported and there is a known association between juvenile xanthogranuloma and childhood leukemia, most commonly juvenile chronic myelogenous leukemia. This case provides further corroboration, that in rare instances, juvenile xanthogranuloma may be associated with hematologic malignancies.     

Localized Severe Scleroderma: A Retrospective Study of 26 Pediatric Patients

Abstract: Juvenile localized scleroderma includes different conditions characterized by skin hardening with increased collagen deposition. Although juvenile localized scleroderma is considered a relatively benign disease, lesions may extend through the dermis, subcutaneous tissue, muscles, and the underlying bone, leading to significant functional and cosmetic deformities. Furthermore, extracutaneous manifestations are described. We retrospectively analyzed a cohort of 26 patients with severe Juvenile localized scleroderma with particular attention to clinical features, therapy, and long‐term outcome. A subgroup of three patients has been further evaluated with infrared thermography. Our findings were consistent with the current literature for demographic, laboratory, and clinical characteristics at disease onset, but, with our patients, the prevalence of extracutaneous manifestations was higher, thus confirming the potential for severe juvenile localized scleroderma to affect organs other than the skin, without increased risk of development toward systemic sclerosis. Correlation between various treatments and clinical endpoint showed that systemic therapy lead to a better outcome: in particular, methotrexate appeared the most effective drug, capable in halting the progression of the disease and sometimes inducing its regression.     

Subcutaneous sarcoidosis as the first manifestation of systemic disease

There are dermatological symptoms in up to 25% of patients with sarcoidosis, and the appearance of specific subcutaneous nodules as a manifestation of this entity is rare. They may even predate other manifestations of sarcoidosis. We present the case of a 38-year-old woman with asymptomatic subcutaneous nodules in the limbs, which corresponded to deep sarcoid granulomas in the histological study. She did not present with any extracutaneous indications. The imaging tests performed revealed right paratracheal adenopathies. This led to the diagnosis of sarcoidosis, in both its subcutaneous and pulmonary forms (stage I). Subcutaneous sarcoidosis is probably an underdiagnosed entity, as fewer than 40 cases are reflected in literature. Its value lies in the fact that it may be the first manifestation of extracutaneous or systemic sarcoidosis, which means that this form of sarcoidosis must be considered in the differential diagnosis of subcutaneous nodular lesions; close follow-up of these patients is also necessary.     

A multistep approach to the diagnosis of rare genodermatoses

Genodermatoses are heritable skin diseases that can cause significant morbidity and mortality. Most of them show characteristic cutaneous findings. Genodermatoses can be associated with extracutaneous system abnormalities. Diagnosing hereditary skin disorders is still a challenging task due to their rarity and diversity, due to diseases evolving over many years, and the initial manifestations not always being diagnostic; therefore, ongoing evaluation and surveillance is often required to make the accurate diagnosis. The algorithm for the diagnosis depends on a combination of thorough clinical and family history clinical examination, laboratory findings, consultation of multiple medical specialists, and molecular analysis. Diagnostic testing targeted at differentiation of similar genodermatoses may be required. Recognition is crucial for the initiation of the treatment for skin manifestations and detection of other extracutaneous abnormalities, including malignancy. Diagnostic accuracy and molecular diagnosis may help in providing a template for ongoing management, testing, and education and prognostication for families of children with genodermatoses.     

Lethal pulmonary involvement of neutrophilic dermatosis following erythropoietin therapy

BACKGROUND: Neutrophilic disease is characterized by aseptic visceral infiltration by normal polymorphonuclear leukocytes that can occur in any organ. Association with an underlying systemic disease, particularly haematological malignancy or inflammatory bowel disease, is frequent. This may produce a multisystem disorder, but diagnosis is usually based on skin lesions because of their clinical and histological accessibility. Pulmonary manifestations are the most common extracutaneous symptoms but may be misdiagnosed, as in our case report. CASE REPORT: A 77-year-old woman with IgA myeloma presented with an inflammatory bullous plaque of the leg coupled with fever lasting one week. The clinical and histological examinations were evocative of a neutrophilic dermatosis such as Sweet's syndrome. Significant improvement was initially obtained with systemic corticosteroids and colchicine. The course became complicated by necrotic neutrophilic papulopustular lesions of the upper limbs and pulmonary manifestations, with fever and decline in overall condition occurring the day after administration of erythropoietin. A hypothesis of septic aetiology prompted antibiotic and antifungal therapy, which remained ineffective. The patient died the day after the second erythropoietin injection. DISCUSSION: This case involved late identification of the aseptic neutrophilic aetiology of pulmonary manifestations. Several factors favouring their appearance and the fatal outcome may be suggested: the existence of a myeloma, association with myelodysplastic syndrome and the possible iatrogenic action of erythropoietin. To the best of our knowledge, this is the first reported case of extracutaneous neutrophilic infiltrate occurring in a patient treated with this haematopoietic hormone.     

A retrospective analysis of 34 patients with cutaneous sarcoidosis assessed in a dermatology department

Background. Sarcoidosis is a multisystem granulomatous disease of unknown aetiology, which most often involves the lungs and lymphatic system. Cutaneous involvement is found in approximately 25% of cases of sarcoid. Most previous studies of cutaneous sarcoidosis have been drawn from populations with defined pulmonary disease, so may represent a population with more systemic involvement. Objective. We describe a cohort of patients with cutaneous sarcoid seen in a dermatology department. Methods. Case records were reviewed for patients with a histopathological diagnosis of noncaseating sarcoidal granuloma on skin biopsy, taken between 1996 and 2005. Results. In total, 34 patient records were analysed; 21 patients were found to have extracutaneous systemic sarcoid and 10 patients had sarcoid localized to the skin. Patients with lupus pernio and with ulcerated sarcoid lesions all had extracutaneous disease. No other cutaneous features, including the extent of cutaneous disease, were found to be predictive of systemic involvement. Conclusions. All patients presenting to a dermatology department with cutaneous sarcoidal granulomas require investigation for systemic sarcoid. Our data suggest that approximately 30% of patients seen in a dermatology clinic with cutaneous sarcoidal granulomas will have disease apparently limited to the skin.     

New clinical syndromes in dermatology

Dermatologists are in the unique position to be able to diagnose serious systemic diseases through skin findings; in addition, cutaneous manifestations can be associated with internal symptoms and clarify the pathogenesis and treatment of challenging new syndromes. Calciphylaxix, now renamed Calcific Uremic Arteriolopathy, primarily affects patients with end-stage renal disease with concomitant hyperphosphatemia, increased calcium-phosphate product and hyperparathyroidism, skin biopsy and wound care are crucial parts of the diagnosis and treatment. Hyperhomocysteinemia may play a very important role in many cutaneous and systemic diseases including, chronic cutaneous wounds, systemic lupus erythematosus, Behcet's disease and psoriasis. Through a skin biopsy and biochemical analysis of the proteoglycans accumulation it may be possible to diagnose a new systemic mucinosis and prevent sudden death in patients with severe mitral valve prolapse. Nephrogenic Fibrosing Dermopathy is a newly described fibrosing disorder occurring in patients with end stage renal disease, the etiology and pathogenesis are still unknown, and the ultimate course of this disease has not been defined.     

Is rosacea a systemic disease?

Rosacea is a chronic inflammatory facial disease occurring world-wide. The incidence of rosacea is increasing with age, with the clinical course being characterized by relapses. The pathogenesis of rosacea is not completely understood, but neurovascular and immunologic mechanisms are involved. Rosacea has a number of known extrinsic triggers that should be avoided, such as sun exposure, heat and cold, alcoholic beverages, and spicy food. Of greater importance is the observation that rosacea may develop as a manifestation of systemic diseases with a significant morbidity and even mortality. Obesity, Helicobacter pylori infection, smoking, and inflammatory bowel disease bear a significant risk for the development of rosacea. Metabolic, psychiatric, and neurologic disorders and certain types of cancer show a significant association with rosacea. The possible link to cardiovascular events is debatable. There are extrafacial and extracutaneous manifestations of rosacea, such as the red scalp syndrome, ocular rosacea, and migraine. Rosacea should be considered a systemic disease.     

Hereditary palmoplantar keratodermas. Part II: syndromic palmoplantar keratodermas – Diagnostic algorithm and principles of therapy

Hereditary palmoplantar keratodermas (PPKs) comprise a large and heterogeneous group of disorders characterized by persistent thickening of the epidermis at palmar and plantar surfaces. Clinical and genetic features of isolated and complex PPKs have been reviewed in part I of this 2‐part review. Here we focus on clinical and molecular classification of syndromic PPKs which are recognized by additional extracutaneous manifestations, in particular deafness, specific mucosal lesions, cardiomyopathy, inborn errors of metabolism, involvement of internal organs or disorders of sexual development. Other genetic diseases, which may show palmoplantar involvement, such as selected subtypes of hereditary epidermolysis bullosa, various hereditary ichthyoses and other keratinization disorders, several ectodermal dysplasias and some multisystem genetic disorders, are also briefly summarized. PPK diagnosis is based on inheritance pattern, age at onset, morphology, distribution and severity of hyperkeratosis, pattern of additional dermatological and systemic manifestations and laboratory findings. Molecular analysis is at present the gold standard to confirm the diagnosis in PPK forms due to mutations in known causative genes. No specific and curative therapy is currently available for PPKs which highly impair patients’ quality of life. Topical treatments are symptomatic and offer only temporary relief. Among systemic treatments, retinoids improve disease symptoms in the majority of patients.     

Extrafacial and generalized granulomatous periorificial dermatitis

BACKGROUND: Granulomatous periorificial dermatitis is a well-recognized entity presenting most commonly in prepubertal children as yellow-brown papules limited to the perioral, perinasal, and periocular regions. The condition is self-limiting and is not associated with systemic involvement. OBSERVATIONS: We reviewed the medical charts of 5 healthy children presenting with extrafacial granulomatous papules in addition to the typical periorificial papules. These extrafacial lesions were clinically and histologically identical to the facial lesions, were self-limiting, and were not associated with systemic involvement. Resolution seemed to be hastened with the use of systemic antibiotic therapy in 4 of the 5 patients. CONCLUSIONS: Extrafacial lesions can occur in granulomatous periorificial dermatitis and do not appear to adversely affect the duration, response to therapy, or risk of extracutaneous manifestations. Overly aggressive evaluation and inappropriate systemic therapy should be avoided.     

A case of erythema elevatum diutinum associated with B-cell lymphoma: a rare distribution involving palms, soles and nails

We report a case of erythema elevatum diutinum (EED) in association with malignant B-cell lymphoma. A 62-year-old man developed EED with an unusual distribution involving the palms, soles and nails. Treatment with dapsone was effective for his skin and nails until he developed generalized lymphadenopathy which turned out to be malignant lymphoma. Many haematological diseases, e.g. IgA paraproteinaemia and myeloma, have been reported in association with EED, but not malignant lymphoma. Even though it may just be a coincidence, we would like to add malignant lymphoma as one of the diseases associated with EED because the activity of EED and malignant lymphoma fluctuated in parallel.     

Sterile neutrophilic folliculitis with perifollicular vasculopathy: a distinctive cutaneous reaction pattern reflecting systemic disease

The authors prospectively encountered skin biopsies from 20 patients which demonstrated a neutrophilic or suppurative and granulomatous folliculitis accompanied by a folliculocentric neutrophilic vascular reaction of Sweet's-like or leukocytoclastic vasculitis subtypes. While in each case the histomorphology raised diagnostic consideration of bacterial folliculitis, patients frequently expressed systemic complaints such as arthritis, fever, and malaise, and special stains for micro-organisms were negative. Among the clinical presentations were folliculitis, vasculitis, acneiform eruptions, vesiculopustular lesions, and erythema nodosum-like lesions, with the legs, arms, and upper back being the most commonly involved sites. Nineteen patients were found to have specific underlying systemic diseases, namely, inflammatory bowel disease, Reiter's disease, Behcet's disease, hepatitis B, connective tissue disease including mixed connective tissue disease and rheumatoid arthritis, scrofuloderma, and hematologic dyscrasias. The other patient had antecedent bacterial sinusitis in the setting of atopy. The folliculocentric nature of these lesions may reflect preferential processing of antigens through the hair follicle and/or homology between bacterial and follicular heat shock proteins in the susceptible host, namely, one who responds excessively to exogenous antigenic triggers. Folliculitis with folliculocentric vasculopathy may be a clue to underlying systemic disease and/or an extracutaneous infection. Certain light microscopic features in concert with the clinical presentation may distinguish such cases from conventional infectious folliculitis.     

European Dermatology Forum S1‐guideline on the diagnosis and treatment of sclerosing diseases of the skin,Part 1: localized scleroderma,systemic sclerosis and overlap syndromes

The term ‘sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first‐ and advanced‐line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this guideline provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes of systemic sclerosis with diseases of the rheumatological spectrum.     

Analysis of 36 Cases of Blaschkoid Dyspigmentation: Reading Between the Lines of Blaschko

Genetic mosaicism indicated by lines of Blaschko pigmentary changes has been described under a number of different and confusing terms, including hypomelanosis of Ito, linear and whorled nevoid hypermelanosis, nevus depigmentosus, and cutis tricolor. Moreover, extracutaneous findings, particularly serious neurologic defects, have been reported in a large number of these cases. We reviewed the cutaneous and extracutaneous findings in 36 patients referred to the Harriet Lane Pediatric Dermatology Clinic, Johns Hopkins University, from June 12, 2008, to May 24, 2009, for evaluation of macular lesions along the lines of Blaschko. Patients with dyspigmentation along the lines of Blaschko and no history of preceding inflammatory skin lesions were identified for inclusion in a database at their initial visit. Information on age at presentation; sex; age when first diagnosed; type, pattern, and location of the pigmentary anomaly; and extracutaneous abnormalities noted on a review‐of‐systems questionnaire and physical examination was recorded for each child. Patients were asked to follow up within 6 to 12 months of the initial visit. Patients included 13 boys and 23 girls ages 3 months to 15 years with lesions noted from birth to 12 years. Lesions were hypopigmented in 21 patients and hyperpigmented in 15. No patients presented with hypopigmented and hyperpigmented lesions. Extracutaneous findings were noted in five children (13.9%). Historically, cases of Blaschkoid hypopigmentation and hyperpigmentation have been associated with a high percentage of extracutaneous manifestations, particularly neurologic and neurodevelopmental defects. In our study, only five patients (13.9%) were noted to have extracutaneous abnormalities, and these findings may have been coincidental. We propose the term ‘Blaschkoid dyspigmentation’ to describe the cutaneous findings. Although serious extracutaneous findings may occur in children with Blaschkoid dyspigmentation and results of careful physical examination and review of systems should direct an evaluation, serious extracutaneous findings occur in a minority of patients.