Pediatric Psychocutaneous Disorders

Psychocutaneous disorders (PCDs) are conditions that are characterized by psychiatric and skin manifestations. Classifications of PCDs and their nomenclature are matters of debate. For the purpose of this review, we adopted the classification that distinguishes primary dermatologic disorders with psychiatric co-morbidity (PDDPC) from primary psychiatric disorders with dermatologic manifestations (PPDDM). PDDPC includes the psychophysiologic disorders such as atopic eczema, psoriasis, vitiligo, and alopecia areata. PPDDM includes impulse control disorders, obsessive-compulsive disorders, factitious disorder, factitious disorder by proxy, self-mutilation, delusions of parasitosis, psychogenic purpura/Gardner-Diamond syndrome, and cutaneous sensory disorders. Diagnosis and treatment of PCDs are challenging and require that the underlying psychopathology be addressed. A specific PCD may have different underlying psychopathologies and, at times, multiple overlapping psychopathologies may coexist. Most often, both non-pharmacologic management and psychopharmacologic treatment are necessary. The choice of psychopharmacologic agent depends on the nature of the underlying psychopathology (e.g. anxiety, depression, obsessive-compulsive disorder, psychosis). This article reviews the spectrum of PPDDM in children.     

The spectrum of cutaneous lymphomas in patients less than 20 years of age

Cutaneous lymphomas are rare in young patients and are mostly represented by mycosis fungoides and its variants and CD30+ lymphoproliferative disorders (lymphomatoid papulosis [LYP] and anaplastic large T-cell lymphoma). We report our observations in a series of 69 patients less than 20 years of age who presented either with primary cutaneous lymphoma (n = 62) or with secondary manifestations of extracutaneous disease (n = 7). Clinicopathologic features permitted classification of the cases into the following diagnostic categories: mycosis fungoides (n = 24, all primary cutaneous), anaplastic large T-cell lymphoma (n = 13, all primary cutaneous), LYP (n = 11, all primary cutaneous), subcutaneous "panniculitis-like" T-cell lymphoma (n = 1, primary cutaneous), small-medium pleomorphic T-cell lymphoma (n = 2, all primary cutaneous), natural killer (NK)/T-cell lymphoma, nasal-type (n = 1, secondary cutaneous), follicle center cell lymphoma (n = 1, primary cutaneous), marginal zone B-cell lymphoma (n = 7, all primary cutaneous), B-lymphoblastic lymphomas (n = 6, 3 primary and 3 secondary cutaneous), specific cutaneous manifestations of Hodgkin disease (n = 1, secondary cutaneous), and acute myeloid leukemia (n = 2, both secondary cutaneous). Cutaneous lymphoma in children should be differentiated from benign skin disorders that may simulate them. In particular, mycosis fungoides and LYP in this age group may present with clinicopathologic features reminiscent of inflammatory disorders such as pityriasis alba, vitiligo, pityriasis rosea, and pityriasis lichenoides et varioliformis acuta. Even in secondary cutaneous lymphomas, skin manifestations may be the first sign of the systemic disease, and a diagnosis may be achieved on examination of histopathologic specimens of a cutaneous lesion. Our study illustrates the wide spectrum of cutaneous lymphomas and leukemias in patients less than 20 years of age and underlines the need for proper interpretation of these lesions by dermatologists and dermatopathologists.     

The spectrum of cutaneous disease in multiple myeloma

BACKGROUND: Multiple myeloma (MM) is a plasma cell dyscrasia characterized by a clonal proliferation of plasma cells that produces a monoclonal protein. There are dermatologic disorders that have been associated with MM, such as amyloidosis, cryoglobulinemia, POEMS syndrome, normolipemic plane xanthoma, and plasmacytoma. The high volume of patients with MM seen at our institution presents an opportunity to define more extensively the spectrum of cutaneous diseases seen in concert with MM. DESIGN: We reviewed 2357 pathology reports of all patients with a diagnosis of MM to find those who had undergone a skin biopsy. Files were searched for bone-marrow diagnosis, and for type and number of transplants. RESULTS: In all, 284 patients yielded 472 skin biopsy specimens (average 1.7/patient). Skin biopsy specimen diagnoses included neoplastic lesions, (111; 73 malignant, 38 benign), graft-versus-host disease (120), drug-related lesions (46), cutaneous eruption of lymphocyte recovery (3), thrombocytopenia-related lesions (9), normolipemic plane xanthoma (1), amyloidosis (1), Sweet's syndrome (7), panniculitis (1), papulosquamous lesions (18), bullous diseases (17), vasculitis (11), infectious lesions (41), granulomatous dermatitis (6), alopecia cicatrisata (1), nonspecific lesions (77), and unrelated lesions (2). CONCLUSIONS: Skin biopsy specimens from patients with MM less than 60 days from transplant most commonly show sequelae of the transplant such as graft-versus-host disease, Grover's disease (as a result of leukocytopenia and fever, waiting for engraftment), drug eruptions, chemotherapy effect, thrombocytopenic effect, cutaneous eruption of lymphocyte recovery, and Sweet's syndrome (possibly as a result of granulocyte-macrophage colony-stimulating factor). Biopsy specimens taken more than 60 days from transplant most commonly show graft-versus-host disease, drug eruptions, and Sweet's syndrome but also show unrelated conditions such as neoplastic lesions, nevi, papulosquamous lesions, vasculitis, infections, and nonspecific changes.     

Cutaneous manifestations of hydroxyurea therapy in childhood: case report and review

Hydroxyurea is commonly used in the treatment of various myeloproliferative disorders. In conventional pediatric clinical practice, its use is limited to benign hematologic conditions such as sickle cell disease and thalassemia. Long-term hydroxyurea use is associated with various adverse mucocutaneous effects including hyperpigmentation, alopecia, leg ulcers, and lichenoid eruptions. We report a 10-year-old boy with chronic myelogenous leukemia who presented with hyperpigmentation of the skin and nails 3 months after the start of hydroxyurea therapy. Melanonychia of all 20 nails with involvement of all three mucocutaneous areas (skin, nails, and mucosa) at presentation was a unique feature in our patient. With the recently increasing pediatric use of hydroxyurea in a variety of disorders, its benign and not so uncommon cutaneous adverse effects are emphasized here.     

Anetoderma arising in cutaneous B-cell lymphoproliferative disease

Anetoderma is circumscribed atrophy of the skin due to a localized deficiency in elastic tissue. It can follow inflammatory skin diseases of several types, and occasionally is present in the skin around neoplasms. There are a few reports of anetoderma in the lesional skin of cutaneous lymphoma. We report on two patients who presented with multiple lesions of anetoderma and who later proved to have low-grade cutaneous B-cell lymphomas. One patient (Patient 1) is a 39-year-old man and the other patient is a 26-year-old woman who is a renal transplant recipient (Patient 2). Some biopsy specimens from the anetodermic skin of Patient 1 appeared to show an urticarial reaction, although plasma cells were present. A large nodule showed lymphoid follicles surrounded by plasmacytoid lymphocytes, with loss of elastic tissue in the adjacent dermis. The plasmacytoid cells stained overwhelmingly for lambda light chain, and staining of the urticarial lesions from this patient also showed a marked majority of lambda positive cells. Immunoglobulin heavy chain gene (IgH) rearrangements showed a dominant clonal pattern in the nodular lesion. We classified the disease in Patient 1 as marginal zone lymphoma and the disease in Patient 2 as a post-transplant lymphoproliferative disorder. Because of the intimate association of anetoderma and cutaneous B-cell lymphoproliferative disorders in these two patients, it seems possible that anetoderma could result from either a local effect of the neoplastic cells or associated inflammatory cells, especially neutrophils as in Case 1. The infiltrates of Case 1 had many interstitial neutrophils and only a few clonal plasmacytoid lymphocytes, indicating that this presentation of B-cell lymphoma can be a diagnostic pitfall. Given these two cases and similar ones in the literature, biopsy of lesional skin in anetoderma should be performed to ensure that lymphomatous infiltrates are not present. Even if plasma cells are sparse, studies to detect clonality are appropriate. Cutaneous B-cell lymphoma can be added to the list of associations of elastolysis and cutaneous lymphoma, which includes granulomatous slack skin (T-cell lymphoma) and cutis laxa (myeloma).     

Recent physiopathological insights in cutaneous lymphocytic infiltrates.

The spectrum of benign cutaneous lymphocytic infiltrates (CLI) includes a variety of entities which are classified on the basis of clinicopathological findings, and of the phenotype of the predominant lymphocytic subset among the skin infiltrate. Major concern has been recelntly given to the clonality status of CLI by using highly sensitive assays based on the PCR amplification of TCR/Ig loci. These studies allowed the characterisation of clonal benighn cutaneous lymphocytic expansions. Other studies have shown evidence of oligoclonal patterns in HIV-associated CD8 cutaneous pseudolymphomas, and functionnal studies of the skin infiltrate further showed that an antigen-driven mechanism was involved in the pathogenesis of this latter entity. Finally, the knowledge in the field of CLI has been improved by the identification of antigens associated with skin-homing properties such as the so-called. Cutaneous Lymphocyte-associated Antigen (CLA) whicis expressed at the surface of most memory T cells infiltrating the dermis in inflammatory conditions.     

Investigation and management of cutaneous arterial insufficiency of the extremities*

The effects of arterial disease may be identified most readily by examination of the skin, and that of the digits often shows the most pronounced changes. The skin may be ischaemic as part of the general arterial insufficiency to a limb or, particularly as with vasospastic disorders, may show the most exaggerated changes whilst other tissues are relatively spared. The spectrum of arterial conditions causing cutaneous arterial insufficiency is wide and ranges from vasospastic disorders, without permanent tissue damage, to conditions where there is necrosis of tissue with loss of function and leading on to gangrene.     

Transforming growth factor-beta overexpression in cutaneous extramedullary hematopoiesis of a patient with myelodysplastic syndrome associated with myelofibrosis

Extramedullary hematopoiesis (EMH) is a relatively rare, but well-documented, manifestation of chronic myeloproliferative disorders. Microscopically, foci of EMH consist of erythroid and myeloid precursors intermixed with megakaryocytes. It typically occurs in the spleen and liver, but very occasionally manifests as cutaneous EMH. We report a 76-year-old Japanese man with cutaneous EMH arising from myelodysplastic syndrome associated with myelofibrosis. His cutaneous manifestations showed multiple skin-colored firm nodules over the head, trunk, and extremities. We detected high plasma levels of transforming growth factor (TGF)-beta1 in our patient. Immunohistochemical analysis of the skin biopsy sample revealed TGF-beta1 overexpression in immature hematopoietic cells and dermal fibroblasts within the cutaneous EMH mass of the dermis. These findings suggest that TGF-beta could play some role in the onset of cutaneous EMH. Five months after his first visit to our dermatologic clinic, the patient developed bone-marrow failure and died. Based on our observations, accelerated malignancy in the bone marrow should be considered in any patient with cutaneous EMH. It is presumed that TGF-beta released from hematopoietic cells within the cutaneous EMH play a critical role in the activation of hematologic malignancy.     

Friends or Foes? Host defense (antimicrobial) peptides and proteins in human skin diseases

Host defense peptides/proteins (HDPs), also known as antimicrobial peptides/proteins (AMPs), are key molecules in the cutaneous innate immune system. AMPs/HDPs historically exhibit broad‐spectrum killing activity against bacteria, enveloped viruses, fungi and several parasites. Recently, AMPs/HDPs were shown to have important biological functions, including inducing cell proliferation, migration and differentiation; regulating inflammatory responses; controlling the production of various cytokines/chemokines; promoting wound healing; and improving skin barrier function. Despite the fact that AMPs/HDPs protect our body, several studies have hypothesized that these molecules actively contribute to the pathogenesis of various skin diseases. For example, AMPs/HDPs play crucial roles in the pathological processes of psoriasis, atopic dermatitis, rosacea, acne vulgaris, systemic lupus erythematosus and systemic sclerosis. Thus, AMPs/HDPs may be a double‐edged sword, promoting cutaneous immunity while simultaneously initiating the pathogenesis of some skin disorders. This review will describe the most common skin‐derived AMPs/HDPs (defensins, cathelicidins, S100 proteins, ribonucleases and dermcidin) and discuss the biology and both the positive and negative aspects of these AMPs/HDPs in skin inflammatory/infectious diseases. Understanding the regulation, functions and mechanisms of AMPs/HDPs may offer new therapeutic opportunities in the treatment of various skin disorders.     

Cutaneous Manifestations of Eating Disorders

Background and Objective: No complete review of the cutaneous manifestations of eating disorders exists. We therefore, set out to review and systematically describe the clinical and histopathologic features of dermatologic conditions associated with anorexia nervosa, bulimia nervosa, and obesity. Differential diagnosis, pathophysiology, laboratory studies, and treatment are also reviewed. Methods: Index Medicus review (1966 to present) using Ovid-MEDLINE. Search terms included eating disorders, anorexia nervosa, bulimia nervosa, eating disorders not otherwise specified (ED-NOS), and obesity, as well as the terms dermatology skin and cutaneous manifestations, with cross-referencing sources. These were combined with our own clinical experience. All relevant publications, including case reports, case series, cohort studies, and histopathologic studies giving at least Level II-3 evidence (evidence from comparisons between times or places with or without the intervention, including dramatic results in uncontrolled experiments), were selected. Conclusions: Forty dermatological signs have been reported in eating disorder patients. Eating disorders have many cutaneous manifestations and cutaneous signs may lead to the diagnosis of an occult eating disorder. The resolution of skin eruptions in eating disorder patients often depends on treatment of the underlying disorder.     

Primary cutaneous anaplastic CD30+ large cell lymphoma

Primary cutaneous anaplastic CD30+ large cell lymphoma (PCALCL) is part of the spectrum of primary cutaneous CD30+ lymphoproliferative disorders together with lymphomatoid papulosis. It affects mainly elderly patients and presents as skin nodules that tend to ulcerate. Histological and immunohistochemical study show the expression of CD30 antigen in more than 75 % of neoplastic cells. Currently it is considered a low grade lymphoma with favourable prognosis and good response to treatments such as local radiotherapy, methotrexate or surgery. We report a 93-year-old patient with ulcerated nodules in her right leg. Histological and immunohistochemical study confirmed the diagnosis of PCALCL, of non-B, non-T origin. The patient was treated with local radiotherapy with progressive resolution of skin nodules and absence of relapse at 6 months follow-up.     

Dermatology in the intensive care unit

We report our experience, and review the literature, concerning ‘intensive care dermatology’. Over a period of 14 months, 27 patients who had significant cutaneous problems were seen in the intensive care unit. These included primary dermatological conditions, multisystem disorders with cutaneous signs, complications of dermatological therapy, and skin conditions developing as complications of intensive care. We discuss the diagnosis and management of dermatological problems in the intensive care unit.     

Case of isolated benign primary cutaneous plasmacytosis in a child

A collection of plasma cells in the skin can represent a broad spectrum of disease entities. Secondary syphilis, primary cutaneous plasmacytoma, primary cutaneous plasmacytosis, cutaneous lymphoid hyperplasia and nodular amyloidosis are considered possible differential diagnoses. We present a case of a 7-year-old girl with an erythematous scaly plaque on her right buttock that had been present for approximately 5 years. Prior to her visit to our department she had been treated at a local dermatology clinic with topical methylprednisolone acetate and topical calcitriol without significant improvement. Histopathological examination revealed psoriasiform hyperplasia, hyperkeratosis, parakeratosis and a band-like or dense perivascular infiltration of plasma cells with a few lymphocytes and histiocytes. Other laboratory tests were within the reference ranges. At our department, the patient was given oral prednisolone along with an intralesional injection of triamcinolone and application of topical methylprednisolone acetate and tacrolimus hydrate to the affected area. The lesion improved significantly but recurred 3 months later. We present a rare case of isolated benign primary cutaneous plasmacytosis in a female pre-adolescent child.     

A study of the spectrum of skin disease occurring in a black population in south-east London

We recorded the diagnosis made in 461 black patients (187 children and 274 adults) attending a dermatology clinic between January and March 1996. In the childhood population, atopic eczema and tinea capitis were the most frequent dermatoses, comprising 63% of diagnoses recorded. In the adult population, acne and acne keloidalis nuchae were seen most frequently. Other conditions observed commonly were eczema, psoriasis, keloid scarring, pityriasis versicolor and postinflammatory changes. Our study demonstrates a wide spectrum of skin disease and includes disorders more common in black skin, disorders unique to black skin, those which present a greater cosmetic disability, and normal findings which have been mistaken for pathological disease.     

Human papillomavirus infection and skin cancer risk in organ transplant recipients

Warts and squamous cell carcinomas are important cutaneous complications in organ transplant recipients. The role of infection with human papillomaviruses (HPV) in the development of cutaneous squamous cell carcinoma is still unclear. An extremely diverse group of HPV types, mainly consisting of epidermodysplasia-verruciformis (EV)-associated HPV types, can be detected in benign, premalignant, and malignant skin lesions of organ transplant recipients. Frequently, there are multiple HPV types present in single skin biopsies. Typically, the prevalence of viral warts rises steadily after transplantation and a strong association exists between the number of HPV-induced warts and the development of skin cancer. The interval between the transplantation to the development of warts is clearly shorter than the interval from transplantation to the diagnosis of the first skin cancer. A comparison of transplant recipients with and without skin cancer, however, showed an equally high prevalence of EV-HPV DNA in keratotic skin lesions in both groups of patients and the detection rate and spectrum of HPV infection in hyperkeratotic papillomas, actinic keratoses, and squamous cell carcinomas was also similar. HPV DNA can frequently be detected in patients with hyperproliferative disorders like psoriasis and antibodies against HPV in patients with regenerating skin (e.g., after extensive second degree burns). Latent infection with EV-HPV seems to be widespread. The hair follicle region might be the reservoir of EV-HPV. The E6 protein from a range of cutaneous HPV types effectively inhibits apoptosis in response to UV-light induced damage. It is therefore conceivable that individuals who are infected by EV-HPV are at an increased risk of developing actinic keratoses and squamous cell carcinomas, possibly by chronically preventing UV-light induced apoptosis.     

Recent physiopathological insights in cutaneous lymphocytic infiltrates

As there were typing errors in the summary of the article by Herve Bachelez in the EJD vol. 9, n 7, a corrected version is published below. The spectrum of benign cutaneous lymphocytic infiltrates (CLI) includes a variety of entities which are classified on the basis of clinicopathological findings, and of the phenotype of the predominant lymphocytic subset among the skin infiltrate. Major concern has been recently given to the clonality status of CLI by using highly sensitive assays based on the PCR amplification of TCR/Ig loci. These studies allowed the characterisation of clonal benign cutaneous lymphocytic expansions. Other studies have shown evidence of oligoclonal patterns in HIV-associated CD8 cutaneous pseudolymphomas, and functional studies of the skin infiltrate further showed that an antigen-driven mechanism was involved in the pathogenesis of this latter entity. Finally, knowledge in the field of CLI has been improved by the identification of antigens associated with skin-homing properties such as the so-called cutaneous lymphocyte-associated antigen (CLA) which is expressed at the surface of most memory T cells infiltrating the dermis in inflammatory conditions.     

Großzelliges B-Zell-Lymphom des Unterschenkels

Primary cutaneous B cell lymphomas are rare malignant lymphoproliferative disorders of the skin. The prognosis is dependent on the clinical and histologic subtype; generally, these disorders show an indolent clinical course. We describe a 80-year-old woman with a large cutaneous B cell lymphoma of the lower leg. In contrast to other variants of cutaneous B cell lymphomas, this entity is characterized by an aggressive clinical course with an unfavorable prognosis. The mean survival rate is approximately 50%. This should be taken into account in the choice of treatment.     

Histiocytosis – cutaneous manifestations of hematopoietic neoplasm and non‐neoplastic histiocytic proliferations

Histiocytoses are rare disorders characterized by the accumulation of cells derived from macrophages, dendritic cells or monocytes in various tissues. There is a broad spectrum of disease manifestations with some subtypes commonly showing skin lesions, while in others, the skin is rarely involved. Here, we describe cutaneous manifestations of histiocytoses belonging to the Langerhans group (L group), the group of cutaneous and mucocutaneous histiocytoses (C group) and the group of Rosai–Dorfman disease (RDD) and related histiocytoses (R group) according to the current classification. Characteristic clinical presentations noted were a rust‐brown colour or xanthomatous aspect in many cases of histiocytoses. Histological criteria for differentiation are described. Immunohistochemistry shows positivity for S100 and CD1a in Langerhans‐cell histiocytoses (LHCH) of the L group, while CD68 positivity with S100 and CD1a negativity are typical in histiocytoses of the C group of cutaneous and mucocutaneous histiocytoses. RDD in the R group shows positivity for S100 and CD68, while CD1a is negative. We further review the pathogenesis of LHCH based on insights on the central role of the mitogen‐activated protein (MAPK) kinase pathway. Common mutations in various histiocytic populations of diverse ontogeny and at different stages of differentiation may be responsible for the diverse clinical picture of this neoplastic entity. For histiocytoses of the C group and R group, a reactive origin is discussed with the exception of the disseminated form of juvenile xanthogranuloma. We suggest exploring the role of an origin from skin residing histiocytes for the isolated cutaneous manifestation in some types. With regard to therapeutic options, skin‐directed therapies are the first choice in limited disease, while systemic chemotherapy has traditionally been used in extensive disease. In Langerhans‐cell histiocytoses and related entities, therapy by BRAF inhibition has led to a breakthrough especially in patients with an activation of the MAPK pathway.     

Granulomatous slack skin: a distinct disorder or a variant of mycosis fungoides?

About 75% of cutaneous lymphomas belong to the group of T-cell lymphomas. Mycosis fungoides is the most common entity in this group. Granulomatous slack skin is a rare form of cutaneous T-cell lymphoma closely related to mycosis fungoides. We present here a patient with areas of lax skin for several years who developed a generalized erythroderma with associated immunoactivation and a deterioration in his general condition. This report discusses clinically and histologically the differential diagnoses, namely granulomatous slack skin and granulomatous mycosis fungoides, and suggests that these 2 disorders are only variants in the broad spectrum of a single disease.     

Cutaneous CD30‐positive lymphoproliferative disorders with CD8 expression: a clinicopathologic study of 21 cases

Lymphomatoid papulosis (LyP) and cutaneous anaplastic large cell lymphoma (ALCL) belong to the spectrum of cutaneous CD30+ lymphoproliferative disorders, an indolent form of T‐cell lymphoproliferative disease. We reviewed 21 cases of CD30+ lymphoproliferative lesions expressing cytotoxic profile (CD8+). Seven cases of cutaneous ALCL, 2 cases of systemic ALCL involving the skin, and 12 cases of LyP. The cases of LyP were predominated by small lymphocytes exhibiting a prominent epidermotropic pattern consistent with either type B or type D LyP. Four cases showed co‐expression of CD56. The ALCL cases included myxoid features, pseudoepitheliomatous change, and an intravascular component. In all cases that were primary in the skin an indolent clinical course was seen while one patient with systemic myxoid ALCL is in remission following systemic multiagent chemotherapy. The paucity of other neutrophils and eosinophils and concomitant granulomatous inflammation were distinctive features in cases of type B and type D LyP. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful differentiating features from an aggressive cytotoxic CD8+ T cell lymphoma. In all cases that were primary in the skin an indolent clinical course was observed. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful in preventing a misdiagnosis of an aggressive cytotoxic CD8+ T cell lymphoma.