Cutaneous sarcoid-like granulomas in primary immunodeficiency disorders

Summary We report the occurrence of cutaneous sarcoid-like granulomas in one patient with common variable immunodeficiency and another with 'thymoma and hypogammaglobulinaemia". To our knowledge, this is the first time that such skin lesions have been described in patients with primary immunodeficiency. These granulomas may be attributed to a combination of interleukin-2 deficiency and a profound CD4 lymphopenia. The lesions are similar to the non-infectious 'papular eruption' associated with human immunodeficiency virus infection, and might reflect a common pathogenic mechanism.     

Cutaneous granulomas associated with primary immunodeficiency disorders

Cutaneous granulomas are uncommon in primary immunodeficiency disorders. We report cutaneous granulomas in a child with ataxia telangiectasia (AT) and compare the clinical course with similar lesions in an adult with common variable immunodeficiency (CVI). A 4-year-old female with AT developed cutaneous granulomas as erythematous plaques. The largest lesion appeared on her left cheek and continued to progress despite treatment with topical and intralesional steroids. Disease control was obtained initially with oral antibiotics and low-dose oral steroids. On cessation of oral steroids, significant relapse of the facial granuloma occurred. Pulsed and then oral steroids were required to stop the disease process leaving significant scarring. The second case is of cutaneous granulomas in a 66-year-old man, with CVI, who presented with an erythematous reticulate rash on the legs. We consider it useful to report this patient here as disease control was obtained in a similar way with systemic immunosuppression. In this patient a combination of oral steroids and azathioprine was used. These cutaneous granulomas are thought to be a manifestation of immune dysregulation. No infectious cause has been found so far. We recommend the use of broad-spectrum antibiotics in conjunction with systemic steroids for progressive granulomas, as these patients are immunosuppressed and infection with an unidentified organism cannot be excluded.     

The primary care physician and the treatment of patients with skin disorders

Scientific advances have altered the nature of primary care medicine. Primary care providers are increasingly asked to care for a broad spectrum of common maladies, including cutaneous disease. We review studies that have compared primary care physicians with dermatologists with respect to the diagnosis and treatment of skin disorders. Though primary care providers play a crucial role in the delivery of health care, the judicious and appropriate use of dermatology consultation should be encouraged.     

Genetic immunodeficiency disorders

In this review, selected immunodeficiency disorders are presented in which the cutaneous signs are distinctive and contribute to the diagnosis of the condition. Among these cutaneous abnormalities are alopecia, cutaneous granulomas, cutaneous infections, atopic-like or seborrheic-like dermatitis, petechiae or purpura, silvery pigmentation, poor wound healing, and telangiectasias. Immunodeficiency should be considered in children with a history of infections that are recurrent, respond poorly to antibiotics, are of increased duration and severity, and/or result from unusual organisms. In addition to their high risk of infection, patients with immunodeficiency disorders have a risk of the development of malignancy that is 10,000 times higher than that of healthy age-matched controls. The underlying molecular basis for most genetic immunodeficiencies is now understood, allowing improved genetic counseling and prenatal diagnosis.     

Is increased 5 alpha-reductase activity a primary phenomenon in androgen-dependent skin disorders?

Testosterone metabolism was investigated in fractions of human skin, enriched in epidermis, dermis, sebaceous glands, and sweat glands, by histologic sectioning of skin punch biopsies, and the results were compared with two culturable skin cells, i.e., keratinocytes and fibroblasts. Since sebocytes could not be brought in culture, metabolism was also investigated in the hamster flank model. In the epidermal tissue of the skin biopsies the predominant metabolite was androstenedione, formed by the enzyme 17 beta-hydroxysteroid dehydrogenase. The same was true for cultured hair follicle keratinocytes. In the deeper skin layers the formation of androstenedione was markedly reduced, whereas the formation of 5 alpha-reduced metabolites was highly increased, with a maximum in the skin fractions containing large sebaceous glands. Cultured shoulder skin fibroblasts showed a markedly different testosterone metabolism compared with the sectioned skin biopsies, suggesting that dermal fibroblasts play a less important role in the overall skin testosterone metabolism. The present approach, allowing the comparison of testosterone metabolism in different substructures of the same skin biopsy provides new evidence that the high 5 alpha-reductase activity in the specific skin fractions must be mainly ascribed to the sebaceous glands. These results render a previous hypothesis, stating that the elevated level of 5 alpha-reductase and subsequent formation of dihydrotestosterone in androgenetic alopecia and acne (usually accompanied by seborrhea) could therefore simply be the consequence of sebaceous gland enlargement, much stronger. This hypothesis is further evaluated by quantitative correlation of sebaceous gland size with enzyme activity in the hamster flank model.     

Immunohistochemical features of cutaneous granulomas in primary immunodeficiency disorders: a comparison with cutaneous sarcoidosis

Background:  Cutaneous granulomas can occur in patients with a primary immunodeficiency disorder. In some cases, an infectious cause cannot be revealed. The pathogenesis of these granulomas still remains to be elucidated. The aim of this study was to study differences or overlap between these rare granulomas and sarcoidosis-related granulomas.
Methods:  Markers for T-cell subsets (CD3, CD4, CD8 and CD45RO), Langerhans' cells (CD1a), macrophages (CD68), B cells (CD20) and NK cells (CD56) were stained immunohistochemically. The amount of CD4+ and CD8+ cells in the granulomas was counted. Results were compared with the CD4+/CD8+ ratio in peripheral blood.
Results:  In the granulomas of two of three patients with a primary immunodeficiency disorder, the cytotoxic T cells (CD8+) outnumbered the T-helper cells (CD4+) with a counted CD4+/CD8+ ratio <<1. In contrast, the granulomas in the cutaneous sarcoidosis patients showed a predominance of CD4+ cells, with CD4+/CD8+ ratios >2.
Conclusions:  A lower CD4+/CD8+ ratio was found in the cutaneous granulomas of patients with a primary immunodeficiency disorder (unclassified combined immunodeficiency, autoimmune lymphoproliferative syndrome and ataxia teleangiectasia) as compared with the patients with cutaneous sarcoidosis. The possible implications of these findings are discussed in this paper.     

Pigmentary disorders in ethnic skin

Pigmentary disorders are commonly seen in ethnic skin. They are psychologically problematic in darker skin. Treatment of many of these disorders remains difficult.     

The spectrum of skin disorders in abdominal stoma patients

BACKGROUND: Skin integrity is essential for the normal usage of a stoma appliance. However, there is little published on the prevalence, nature or management of stoma-related skin disorders. Objectives To document stoma-related skin disorders in a large cohort of patients. METHODS: We sent a postal questionnaire to all surviving patients who had had abdominal stoma surgery at Hope Hospital, Salford, U.K. in the 10 years from 1 January 1989. Those reporting skin disease were invited to attend a clinic run by a dermatologist and a stoma-care specialist nurse. All lesions were categorized and swabs taken for microbiological examination. RESULTS: Of 525 surviving patients, 325 (62%) replied to the questionnaire. Of these, 73% reported a skin problem that had affected normal stoma bag use. Dermatoses included irritant reactions, particularly from leakage of urine or faeces (42%); pre-existing skin diseases, principally psoriasis, seborrhoeic dermatitis and eczema (20%); infections (6%); allergic contact dermatitis (0.7%) and pyoderma gangrenosum (0.6% annual incidence). A further 15% of patients with skin problems had persistent or recurrent dermatitis not explained by allergy, frank infection or faecal irritation. This responded to short-term treatment with topical corticosteroids. Further investigation is under way into its pathogenesis. CONCLUSIONS: Skin disorders are common in stoma patients, and various patterns can be recognized and effectively treated.     

Mechanisms in allergic skin disorders

Background Allergic skin disorders are initiated and maintained through the action and interaction between resident tissue cells, infiltrating leucocytes and mediators. Review The major cellular components of the skin immune system are keratinocytes, dendritic cells such as epidermal Langerhans cells (LCs) and dermal dendritic cells, mast cells and fibroblasts. Following an allergenic stimulus, inflammatory and immunocompetent cells accumulate in the epidermis and dermis, giving rise to specific clinical and histological manifestations. Leucocytes which accumulate in the inflammatory focus attract more leucocytes and stimulate the resident cell population. Primary mediators, released by resident cells upon stimulation, play a vital role in initiating and controlling inflammation. The mediators induce vascular endothelial cells to express adhesion molecules, which mediate migration of leucocytes into the dermis, where chemotactic factors attract them to the inflammatory focus. Activation of trapped T-lymphocytes by antigen-presenting cells (APCs) is followed by the release of inflammatory cytokines. Allergic contact dermatitis (ACD) depends on the activation of specifically sensitised T-cells, and epidermal LCs are the primary APCs. Most contact allergens are small, chemically reactive moleculed and CD4⁺ Th1 type T-cells are the target cells. Atopic dermatitis is a chronic eczematous condition, involving antibody IgE, LCs and dermal dendritic cells as the APCs, with Th2 T-lymphocytes as the target cells. Urticaria comprises a heterogeneous group of conditions, characterised by a wheal and flare reaction. Mast cells are the principal source of mediators involved and histamine is the most important of these.     

Photosensitivity skin disorders in childhood

Photosensitivity in childhood is caused by a diverse group of diseases. It usually indicates idiopathic photodermatoses, first of all polymorphic light eruption. It may be an early symptom of genetic disorders such as porphyria or very rare genophotodermatoses. Photosensitivity secondary to topical or systemic external agents as well as photoexacerbated dermatoses is not so frequent in childhood. Here we present our experience with childhood photosensitivity skin diseases collected over a 40-year period.     

Pigmentary disorders in oriental skin

Brown hyperpigmented disorders may be melanotic in which there is a normal number of epidermal melanocytes but melanin pigment is increased in the epidermis (eg, melasma), melanocytotic, in which melanocytes are increased (eg, café-au-lait macules), and nonmelanotic hyperpigmentation (eg, minocycline pigmentation). Blue hyperpigmented disorders may also be melanotic in which there is a normal number of epidermal melanocytes, but melanin pigment is present in the upper dermis (eg, gray/slate pigmentation in Riehl's melanosis), melanocytotic in which melanocytes are present in both the epidermis and dermis (eg, blue pigmentation in Nevus Ota and Mongolian spot), and nonmelanotic hyperpigmentation in which pigment is present in the deep dermis (eg, blue pigmentation in tattoos). Hypomelanosis (leukoderma) may be divided histopathologically into melanocytopenic disorders on which melanocytes are absent (eg, Vogt-Koyanagi-Harada syndrome and vitiligo), melanopenic disorders in which melanocytes are present but melanin is reduced (eg, nevus depigmentosus and incontinentia pigmenti achromians), and nonmelanotic disorders in which melanin pigmentation is unaffected (nevus anemicus) and the pigmentary abnormality is caused by something other than melanin. There are numerous pigmentary disorders in the oriental skin, and some of them are either characteristic to or established in the orientals. Importantly, a number of congenital hypermelanotic and hypomelanotic diseases (eg, nevus depigmentosus, incontinentia pigmenti, and incontinentia pigmenti achromians, take a distribution following to the Blaschko's line.     

Suicide risk in skin disorders

Suicide accounts for about 1,000,000 deaths worldwide every year and is among the leading causes of death in young adults. Reports of high prevalence of suicidal ideation and increased suicide risk in several skin diseases raised concerns about deliberate self-harm in dermatological patients. The literature consistently points to an increased suicide risk in patients with psoriasis, atopic dermatitis, and acne, with higher risk in patients in whom the skin condition is associated with clinically significant emotional distress, changes in body image, difficulties in close relationships, and impaired daily activities. Other risk factors for suicide include a history of suicide attempts, severe mental or physical disorders, alcoholism, unemployment, bereavement or divorce, and access to firearms or other lethal means. Dermatologists may play an important role in recognizing suicidal ideation and preventing fatal self-harm in their patients. Increasing dermatologists' awareness of the issue of suicide and developing mental health consultation-liaison services within dermatology settings would be instrumental in contributing to suicide prevention in this population.     

Spectrum of skin disorders in human immunodeficiency virus-infected patients in Singapore and the relationship to CD4 lymphocyte counts

BACKGROUND: Skin disorders are extremely common and cause significant morbidity in human immunodeficiency virus (HIV)-infected individuals. There are few data on their prevalence and association with CD4 counts in Asians. AIM: To evaluate the prevalence of skin disorders in ambulatory HIV-infected individuals attending a specialized skin clinic in Singapore and the association with the degree of immunosuppression. METHODS: A cross-sectional study on skin disorders in HIV-positive outpatients in the Communicable Disease Centre of Singapore was performed. The association between skin disease prevalence and CD4 count was evaluated using logistic regression. RESULTS: Ninety-six patients (male : female, 8 : 1) were enrolled. The most common mode of HIV transmission was heterosexual (75%), followed by homosexual/bisexual contacts (22%), and intravenous drug abuse (3%). The distribution of patients in terms of current CD4 cell counts was as follows: 38.5% with less than 50 x 10(6)/L, 25% with between 50 and 199/microL, and 36.5% with at least 200 x 10(6)/L. The most common skin disorder was pruritic papular eruption (PPE) of HIV infection (31 cases), followed by psoriasis (24), seborrheic dermatitis (18), xerosis (17), herpes simplex (17), and adverse drug eruptions (17). A CD4 cell count of less than 200 x 10(6)/L was significantly associated with a higher number of skin disorders (P = 0.002) and the development of psoriasis [odds ratio (OR), 8.97; 95% confidence interval (CI), 1.70-47.16; P = 0.010], PPE (OR, 3.40; 95% CI, 1.21-9.53; P = 0.020), and adverse drug eruption (OR, 5.83; 95% CI, 1.21-28.00; P = 0.028). CONCLUSIONS: A preponderance of inflammatory dermatoses and an absence of skin tumors characterized this study. A low CD4 cell count was associated with a higher number of skin disorders and an increased incidence of PPE, psoriasis, and adverse drug eruptions.