Granulomatous slack skin syndrome: Report of a unique case.

Granulomatous slack skin syndrome is a rare variant of cutaneous T-cell lymphoma (mycosis fungoides). It is characterized clinically by redundant skin folds, which show a predilection towards flexural areas such as the axilla and the groin. Histologically, it shows a granulomatous T-cell infiltrate and loss of elastic tissue. It has an indolent but progressive course; and is usually refractory to treatment. We report a unique case of slack skin syndrome, sparing the classical sites with rapid and unusual involvement of non-intertriginous areas.

Keratoderma-like T cell dyscrasia: A report of 13 cases and its distinction from mycosis fungoides palmaris et plantaris.

BACKGROUND: Atypical epitheliotropic T cell lymphocytic infiltrates are commonly encountered in routine and consultative dermatopathology practices and typically do not represent mycosis fungoides. Other conditions can mimic certain light microscopic and phenotypic findings encountered in mycosis fungoides, comprising a diverse spectrum of conditions including the lymphomatoid drug reaction, collagen vascular disease, viral hypersensitivity reactions and cutaneous T cell dyscrasia. AIMS: To examine biopsies obtained from cutaneous T cell dyscrasia localized to the palms and soles and to evaluate whether it exhibits a morphologic and pathogenetic continuum with mycosis fungoides plantaris et palmaris. METHODS: We examined 13 biopsies showing an epidermotropic superficial lymphocytic infiltrate from thirteen patients who presented with a palmar and/or plantar keratoderma without other sites of cutaneous involvement. Conventional light microscopy, immunophenotyping and clonality studies were carried out. The clinical features were recorded. RESULTS: Biopsies showed a variably dense, superficial, angiocentric CD4 or CD8 dominant lymphocytic infiltrate accompanied by a non-destructive pattern of epidermotropism. Low-grade cerebriform atypia along with variable diminution in the expression of CD7 and CD62L was noted. In three cases, statins were suspected to be the cause. Due to lack of familiarity with the entity, treatment interventions were inconsistent and not aggressively pursued. There was no evidence of disease progression to mycosis fungoides in any case. LIMITATIONS: The limitations of this study include the lack of long-term follow up and information on the nature of the therapeutic interventions and responses to treatment. CONCLUSION: The spectrum of cutaneous lymphoid dyscrasias should be expanded to include cases manifesting as palmo-plantar keratoderma. These cases are to be distinguished from mycosis fungoides palmaris et plantaris. As with other forms of cutaneous lymphoid dyscrasia, the lesions tend to be persistent. The course however, is indolent in most cases.

Spontaneous regression of a congenital melanocytic nevus.

Congenital melanocytic nevus (CMN) may rarely regress which may also be associated with a halo or vitiligo. We describe a 10-year-old girl who presented with CMN on the left leg since birth, which recently started to regress spontaneously with associated depigmentation in the lesion and at a distant site. Dermoscopy performed at different sites of the regressing lesion demonstrated loss of epidermal pigments first followed by loss of dermal pigments. Histopathology and Masson-Fontana stain demonstrated lymphocytic infiltration and loss of pigment production in the regressing area. Immunohistochemistry staining (S100 and HMB-45), however, showed that nevus cells were present in the regressing areas.

Cutaneous CD4+/CD56+ hematodermic neoplasm.

CD4+/CD56+ hematodermic neoplasm, formerly known as blastic NK cell lymphoma, is a rare and aggressive neoplasm with a high incidence of cutaneous involvement, risk of leukemic dissemination and poor prognosis. The characteristic features are expression of the T helper inducer cell marker CD4 and the NK-cell marker CD56 in the absence of other T cell or NKcell specific markers. Because of the rarity of this disease, we describe a 48 year old woman suffering from CD4+/CD56+ hematodermic neoplasm on her cheek without leukemic infiltration.

Increased tissue leptin hormone level and mast cell count in skin tags: a possible role of adipoimmune in the growth of benign skin growths.

BACKGROUND: Skin tags (ST) are common tumors. They mainly consist of loose fibrous tissue and occur on the neck and major flexures as small, soft, pedunculated protrusions. Decrease in endocrine, hormone level and other factors are thought to play a role in the evolution of ST. Leptin is an adipocyte-derived hormone that acts as a major regulatory hormone for food intake and energy homeostasis. Leptin deficiency or resistance can result in profound obesity and diabetes in humans. A role of mast cell in the pathogenesis of ST is well recognized. AIMS: To investigate the role of leptin in the pathogenesis of ST and to clarify whether there is a correlation between mast cell count and leptin level in ST. METHODS: Forty-five skin biopsies were taken from 15 patients with ST. From each patient, a biopsy of a large ST (length >4 mm), a small ST (length <2 mm) and a normal skin biopsy (as a control) were taken. The samples were processed for leptin level. Skin biopsies were stained with hematoxylin and eosin and toluidine blue-uranyl nitrate metachromatic method for mast cell count was used. RESULTS: There was a significant increased level of leptin in the ST compared to the normal skin. It was highly significant in small ST than in big ST (P = 0.0001) and it was highly significant in small and big ST compared to controls, P = 0.0001 and P = 0.001, respectively. There was a significant increase in mast cell count in the ST, which did not correlate with the increased levels of leptin. CONCLUSION: This is the first report to demonstrate that tissue leptin may play a role in the pathogenesis of ST. The significant increase in the levels of leptin and mast cell count in ST may indicate a possible role of adipoimmune in the benign skin growths.

Thalidomide and analogues: potential for immunomodulation of inflammatory and neoplastic dermatologic disorders.

Thalidomide and analogues are a class of immunomodulatory drugs or IMiDS. Thalidomide was initially approved by the U.S. Food and Drug Administation for treatment of erythema nodosum in leprosy and is now approved for multiple myeloma as well. A second generation IMiD, lenalidomide, is also approved for multiple myeloma and refractory myelodysplastic syndrome. Discovery of this class of drugs has been serendipitous and empirical, as the drug targets have been unknown. In this review, the authors integrate recent identification of drug targets of IMiDS, which include the inducible form of nitric oxide synthase (iNOS), Rho GTPase and caspase-1, with the developments in the understanding of the molecular biology of human inflammatory, infectious and neoplastic skin disorders. Because thalidomide reemerged through leprosy, the original disease classified by the T cell, the authors have also emphasized advances in the understanding of T-cell subsets in human skin disorders.

Leprosy and Kaposi sarcoma presenting as an immune reconstitution inflammatory syndrome in a patient with AIDS.

The simultaneous presence of infectious organisms within cutaneous lesions of Kaposi sarcoma in persons with AIDS has been demonstrated. We describe a patient with concurrent leprosy and Kaposi sarcoma presenting as an immune reconstitution inflammatory syndrome in the setting of AIDS.

Skin lesions in renal transplant recipients: a single center analysis.

BACKGROUND: The chronic use of immunosuppressants in renal transplant recipients (RTRs) predisposes them to a variety of skin manifestations. Studies on skin lesions in RTRs from India have been limited. AIM: To study the prevalence and clinical spectrum of skin diseases in RTR in patients attending the Nephrology clinic of a tertiary care hospital in South India. METHODS: Between October 2002 and June 2003, 365 RTRs were evaluated for skin lesions, including 280 examined after renal transplant (group A) and 85 examined once before and then monthly after transplant for a period of 6 months (group B). RESULTS: A total of 1163 skin lesions were examined in 346 RTRs (94.7%) including lesions of aesthetic interest (LAI) [62.3%] followed by infections [27.3%]. All LAI were drug-related manifestations, making it the most common skin lesion, while fungal (58.7%) and viral (29.3%) infections constituted majority of lesions caused by infection. Lesions related to neoplasms were relatively uncommon (2.1%) and all lesions were benign. Miscellaneous lesions constituted 8.3% of skin lesions, which included vaccine-induced necrobiotic granulomas at the site of Hepatitis B vaccination and acquired perforating dermatoses. CONCLUSION: Skin lesions among RTRs from India consist predominantly of drug-related LAI and infections and are different from the West in view of the paucity of neoplastic lesions.

Screening, early detection, and trends for melanoma: current status (2000-2006) and future directions

In the past 5 years, there have been notable strides toward the earlier recognition and discovery of melanoma, including new technologies to complement and augment the clinical examination and new insights to help clinicians recognize early melanoma. However, incidence and mortality rates throughout most of the developed world have risen over the past 25 years, while education and screening, potentially the best means for reducing the disease, continue to be severely underutilized. Much progress needs to be made to reach middle-aged and older men and persons of lower socioeconomic status who suffer a disproportionate burden of death from melanoma. Worldwide melanoma control must also be a priority, and comprehensive educational and screening programs should be directed to Northern Ireland and a number of Eastern European nations, whose 5-year survival rates range between 53% and 60%, mirroring those of the United States and Australia more than 40 years ago. LEARNING OBJECTIVE: After completing this learning activity, participants should be aware of the most recent melanoma epidemiologic data, both in the United States and internationally; worldwide early detection and screening programs; clinical strategies to recognize and improve the detection of early melanoma; the latest technologies for early detection of melanoma; and public and professional education programs designed to enhance early detection.

Skin cancer in skin of color / Skin cancer in skin of color

Skin cancer is less common in persons with skin of color than in light-skinned Caucasians but is often associated with greater morbidity and mortality. Thus, it is crucial that physicians become familiar with skin cancer in persons of color so as to maximize the likelihood of early detection of these tumors. In dark-skinned ethnic groups, squamous cell carcinoma is most common; squamous cell carcinoma and melanoma usually occur on nonsun-exposed sites; and ultraviolet radiation is not an important etiologic factor for skin cancer with the exception of basal cell carcinoma. Races of intermediate pigmentation, such as Hispanics and Asians, share epidemiologic and clinical features of dark-skinned ethnic groups and Caucasians. Skin cancers pose a significant risk in skin of color and clinicians should focus on preventive measures in these groups such as regular skin exams, self-examination, public education, and screening programs. LEARNING OBJECTIVE: At the completion of this learning activity, participants should be familiar with the epidemiology and unique clinical features of skin cancer in skin of color and be aware of strategies to prevent skin cancer in skin of color.

Primary cutaneous multifocal CD30+ anaplastic large cell lymphoma.

A 45-year-old male presented with asymptomatic tumors all over the body. The tumors showed no signs of ulceration or regression. There were generalized, nontender, firm to hard enlarged lymph nodes without hepatosplenomegaly. Biopsy and immunophenotyping revealed CD 30+ anaplastic primary cutaneous large cell lymphoma. Primary cutaneous anaplastic large cell lymphoma is characterized by single or grouped reddish-brown tumor nodules, which frequently tend to ulcerate. Secondary involvement of lymph nodes is seen in only 25%. The lesions responded dramatically to chemotherapy, but recurred.

The role of toll-like receptors in the pathogenesis and treatment of dermatological disease.

Toll-like receptors (TLR) are crucial players in the innate immune response to microbial invaders. These receptors are expressed on immune cells, such as monocytes, macrophages, dendritic cells, and granulocytes. Importantly, TLR are not only expressed by peripheral blood cells, but their expression has been demonstrated in airway epithelium and skin, important sites of host-pathogen interaction. Host cells expressing TLR are capable of recognizing conserved pathogen-associated molecular patterns, such as lipopolysaccharide and CpG DNA, and their activation triggers signaling pathways that result in the expression of immune response genes and cytokine production. As TLR are instrumental in both launching innate immune responses and influencing adaptive immunity, regulation of TLR expression at sites of disease such as in leprosy, acne, and psoriasis may be important in the pathophysiology of these diseases. Furthermore, since TLR are vital players in infectious and inflammatory diseases, they have been identified as potential therapeutic targets. Indeed, synthetic TLR agonists such as imiquimod have already established utility in treating viral pathogens and skin cancers. In the future, it seems possible there may also be drugs capable of blocking TLR activation and thus TLR-dependent inflammatory responses, providing new treatment options for inflammatory diseases.

Clinical classification of African Kaposi's sarcoma: time for reappraisal.

PIP: African Kaposi's sarcoma (KS) remains a medical curiosity which continues to intrigue and elude medical science. While impaired cell-mediated immunity has been associated with some subtypes of African KS before and after the advent of AIDS, its role in the pathogenesis of African KS has never been defined. Determining the role of host immunity in the pathogenesis of African KS could, however, yield important insights into the tumor. The author notes that immune impairment from causes other than AIDS could exert similar influences upon the biological and clinical behavior of African KS. Unfortunately, preoccupation with the relationship between AIDS and atypical KS has overshadowed interest in the relation between immunosuppression in general and African KS. That different morphologic subtypes of African KS have identical histology suggests that they are manifestations of the same disease. Clinical manifestations of African KS in a susceptible host is probably determined by a complex interplay between host immunity and putative cofactors such as infectious agents, KS antigens, hormones, and genetic and environmental factors. African KS has a clinical spectrum ranging from localized to generalized. Hosts with relatively good cellular immunity develop localized lesions, while hosts with markedly impaired immunity develop generalized cutaneous or lymphadenopathic KS. The author draws an analogy with leprosy to help clarify the role of host immunity in the clinical manifestations and behavior of African KS.^ieng

Imbalance in T cell subsets in human diseases.

T cell subsets have been evaluated in 232 patients with various immunological diseases and 41 normal individuals used as a control group. An increase in the helper/suppressor ratio (OKT4:OKT8) was often noted in multiple sclerosis (acute attacks and progressive forms), autoimmune hemolytic anemia (without steroids), membranous and IgA-deposit glomerulonephritis, HBs-negative chronic active hepatitis, lepromatous patients with erythema nodosum, and myasthenia gravis. Ratios were usually normal in membranoproliferative nephritis, in lupus erythematosus (at least in steroid treated cases) and in nephrotic syndrome. High values of helper cells have been found in Sezary's syndrome (with low or no suppressor cells) and in mycosis fungoides. Variable data have been obtained in immunodeficiency syndromes. These data have been correlated with age, sex and clinical parameters, as well as with other immunological tests (E rosettes, mitogen responses, mixed lymphocyte reaction, Concanavalin A-induced suppression). From our investigations we have concluded that the study of OKT antibody-defined T cell subsets offers a valuable technique for the further investigation of human immunological diseases.