Phototherapy, photodynamic therapy and photophoresis in the treatment of connective-tissue diseases: a review.

Connective-tissue disorders, which include lupus erythematosus, morphoea/scleroderma and dermatomyositis, are characterized by cutaneous manifestations that are sometimes resistant to conventional therapy. Light treatments, which include phototherapy, photodynamic therapy (PDT) and photopheresis, are routinely utilized in the treatment of dermatological conditions and may provide unique mechanisms of action in the treatment of these connective-tissue disorders. The objective of this study is to conduct a review of the literature that describes the use of phototherapy, PDT and photopheresis in the treatment of lupus erythematosus, morphoea/scleroderma and dermatomyositis. A MEDLINE search was conducted to find articles that discuss treatment of connective-tissue diseases with light therapies and more than 30 publications that discuss light therapy for these diseases were identified. These range in design from case reports to randomized, prospective trials. Study outcomes and details were summarized and presented within each connective-tissue disease by light therapy modality, which includes phototherapy, PDT and photopheresis. Although there is a known association between photosensitivity and connective-tissue diseases, light therapies, when used appropriately, may be legitimate therapeutic options for recalcitrant cutaneous manifestations in lupus erythematosus, morphoea/scleroderma and dermatomyositis.

Methotrexate in the treatment of pemphigus vulgaris: experience in 23 patients.

BACKGROUND: The standard treatment for patients with pemphigus vulgaris has long consisted of high-dose glucocorticoids. Studies regarding the use of methotrexate in pemphigus vulgaris date back to 1968, but few have quantitatively described a steroid-sparing effect conferred by methotrexate. OBJECTIVES: We sought to evaluate the efficacy of methotrexate in 23 patients with pemphigus vulgaris, using the drug's steroid-sparing effect as the primary indicator of clinical improvement. We investigated whether methotrexate could be used as monotherapy in some patients. METHODS: Retrospective chart review was used to analyse the records of patients with pemphigus vulgaris treated with methotrexate at the New York University Langone Medical Center for at least three consecutive months between 2000 and 2012. Diagnosis was made by tissue biopsy and either direct or indirect immunofluorescence tests and enzyme-linked immunosorbent assay. RESULTS: Improvement in clinical symptoms was observed in 91% of patients. Sixteen patients (70%) were eventually weaned completely off prednisone, with a mean time to discontinuation of 18 months. In total 23% of patients enjoyed a partial steroid-sparing effect, requiring a mean maintenance dose of prednisone of 6·75 mg daily. Two patients (9%) developed possible adverse events requiring cessation of the drug, and one patient received no therapeutic benefit from the drug. CONCLUSIONS: Methotrexate is a useful and well-tolerated therapy with considerable steroid-sparing effect in patients with pemphigus vulgaris. It may be considered a first-line adjuvant therapy in the treatment of this difficult disease.

Murine model of atopic dermatitis associated with food hypersensitivity.

BACKGROUND: Atopic dermatitis (AD) is an eczematous skin eruption that generally begins in early infancy and affects up to 12% of the population. The cause of this disorder is not fully understood, although it is frequently the first sign of atopic disease and is characterized by an elevated serum IgE level, eosinophilia, and histologic tissue changes characterized early by spongiosis and a CD4(+) T(H)2 cellular infiltrate. Hypersensitivity to foods has been implicated as one causative factor in up to 40% of children with moderate-to-severe AD. OBJECTIVE: The purpose of this study was to establish a murine model of food-induced AD. METHODS: Female C3H/HeJ mice were sensitized orally to cow's milk or peanut with a cholera toxin adjuvant and then subjected to low-grade allergen exposure. Histologic examination of skin lesions, allergen-specific serum Ig levels, and allergen-induced T-cell proliferation and cytokine production were examined. RESULTS: An eczematous eruption developed in approximately one third of mice after low-grade exposure to milk or peanut proteins. Peripheral blood eosinophilia and elevated serum IgE levels were noted. Histologic examination of the lesional skin revealed spongiosis and a cellular infiltrate consisting of CD4(+) lymphocytes, eosinophils, and mast cells. IL-5 and IL-13 mRNA expression was elevated only in the skin of mice with the eczematous eruption. Treatment of the eruption with topical corticosteroids led to decreased pruritus and resolution of the cutaneous eruption. CONCLUSION: This eczematous eruption resembles AD in human subjects and should provide a useful model for studying immunopathogenic mechanisms of food hypersensitivity in AD.

Cellular and immunologic mechanisms in atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease that is frequently associated with respiratory allergies. Atopic dermatitis develops as a result of a complex interrelationship of environmental, immunologic, genetic, and pharmacologic factors. Efforts to understand the relative contributions of these factors have led to research seeking to identify the relevant effector cells and mediators involved in the pathogenesis of atopic dermatitis. These factors include the pattern of local cytokine release, the differentiation of helper T cells, multiple roles of IgE, skin-directed cell responses, infectious agents, and superantigens. This article reviews these cellular and immunologic mechanisms underlying atopic dermatitis and discusses how an understanding of their role in the inflammatory process may lead to improved treatments for atopic dermatitis.

Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part II, safety.

In two randomized, double-blind, multicenter studies, a total of 631 adult patients with moderate to severe atopic dermatitis applied tacrolimus ointment (0.03% or 0.1%) or vehicle twice daily for up to 12 weeks. The mean percent body surface area (%BSA) affected at baseline was 45%, and 56% of patients had severe atopic dermatitis. As previously reported, these studies showed that tacrolimus ointment was superior to vehicle for all efficacy parameters measured. This report focuses on the safety of tacrolimus ointment in these studies. The most common adverse events were the sensation of skin burning, pruritus, flu-like symptoms, skin erythema, and headache. Skin burning and pruritus were more common among patients with severe or extensive disease; these events were usually brief and were resolved during the first few days of treatment. Common adverse events with a significantly higher incidence in one or both of the tacrolimus ointment groups than in the vehicle group included skin burning, flu-like symptoms, and headache. More patients in the vehicle group discontinued the study because of an adverse event than in either of the tacrolimus ointment groups. There were no notable or consistent changes in any laboratory variables. Tacrolimus was not detected in 80% of blood samples collected. Measurable concentrations of tacrolimus were transitory and were not associated with adverse events. Tacrolimus ointment is a safe therapy for the treatment of adult patients with atopic dermatitis on the face, neck, or other body regions.

Mastocytosis and the skin.

The most frequent site of organ involvement in individuals with any form of mastocytosis is the skin. Cutaneous lesions include urticaria pigmentosa, mastocytoma, diffuse and erythematous cutaneous mastocytosis, and telangiectasia macularis eruptiva perstans. The major histologic feature is an increase in the number of mast cells in the dermis. Treatment depends on the type of skin lesions.

Allergic contact and photoallergic contact dermatitis to plant and pesticide allergens.

BACKGROUND: The panel of patch test allergens used for the evaluation of patients with suspected photoallergy typically does not include plant and pesticide allergens. The prevalence of allergic contact dermatitis and photoallergic contact dermatitis to plant and pesticide allergens was determined for this subgroup of patients. OBSERVATION: Positive reactions were detected in 12 of 26 patients who were tested with our photoallergen series: 5 with allergic contact dermatitis, 5 with photoallergic contact dermatitis, and 2 with both. Four of the 12 patients had positive patch and photo-patch test reactions to plant allergens, pesticide allergens, or both. The positive patch test reactions were to the plants Taraxacum officinale (dandelion) and Tanacetum vulgare (tansy) and to the pesticides folpet and captafol. Positive photo-patch test reactions were to the pesticides folpet and captan. The histories of the patients suggested that 2 or 3 of the 4 patients had clinically relevant reactions. In the other 8 patients, positive reactions to the patch and photo-patch tests included fragrances, sunscreens, and antibacterial agents. CONCLUSION: Plant and pesticide allergens should be included in the patch and photo-patch test series used for the evaluation of patients with suspected photoallergy.

Allergic and immunologic skin disorders.

The skin represents a unique immunologic organ poised to protect the host from invading organisms and environmental antigens. The skin is also an important target for a variety of allergic and autoimmune responses. Mast cells are key to the pathogenesis of urticaria, angioedema, and mastocytosis. Atopic dermatitis is the consequence of an immunoregulatory abnormality resulting in a skin-directed T helper type 2 response. Allergic contact dermatitis is an example of classic delayed type hypersensitivity. Circulating autoantibodies against the epidermis are a key mechanism by which bullous skin diseases occur.

UVB phototherapy is an effective treatment for pruritus in patients infected with HIV.

BACKGROUND: Pruritus in patients positive for HIV may be debilitating. OBJECTIVE: Our purpose was to evaluate the efficacy of UVB therapy in the treatment of pruritus in patients positive for HIV. METHODS: Twenty-one male HIV-positive patients with intractable pruritus (14 with eosinophilic folliculitis and 7 with primary pruritus) were treated three times weekly with UVB phototherapy. Pruritus was quantified with use of a subjective score of 0 (none) to 10 (severe). RESULTS: Mean CD4 counts at the initiation of therapy were 91.0 +/- 31.9 cells/microliter. Pruritus scores before and after treatment were 8.6 +/- 0.4 and 2.2 +/- 0.5, respectively (p < 0.001). The mean number of treatments to achieve maximal improvement was 20.7 +/- 2.3, with a cumulative UVB dose of 3399.1 +/- 597.4 mJ/cm2. No significant difference was found between the group with eosinophilic folliculitis and the group with primary pruritus. CONCLUSION: UVB phototherapy can produce significant relief of pruritus and improvement in the quality of life in patients positive for HIV.

Chronic actinic dermatitis associated with human immunodeficiency virus infection.

Chronic actinic dermatitis is a photodistributed, eczematous dermatitis that preferentially affects elderly men and persists for months to years. Its occurrence in individuals infected with human immunodeficiency virus (HIV) has been described in five patients. We report four additional cases of this uncommon, chronic photodermatosis associated with HIV infection. In two of the patients, photosensitivity was a presenting disorder leading to the diagnosis of HIV infection. All patients were men of skin type VI with a mean age of 50 years, all had decreased minimal erythema doses to ultraviolet B, three of the four patients had decreased minimal erythema doses to ultraviolet A and all had CD4 cell counts of < 200 x 10(6)/L.

Results of evaluation of 203 patients for photosensitivity in a 7.3-year period.

BACKGROUND: Although photosensitivity disorders have been well described, their incidence in a referral institution had not been studied. OBJECTIVE: The purpose of this study was to evaluate the incidence of photosensitivity disorders, including photocontact dermatitis, in an academic medical center. METHODS: The results of the assessment of 203 consecutive patients, all of whom had phototests, referred for the evaluation of photosensitivity disorders during a 7.3-year period were reviewed. RESULTS: The mean age was 50 years, and 63% of the patients were women. The most frequent diagnoses were polymorphous light eruption (26% of the total patient population), chronic actinic dermatitis (17%), photoallergic contact dermatitis (8%), systemic phototoxicity to therapeutic agents (7%), and solar urticaria (4%). Positive photopatch reactions, patch test reactions, or both were observed in 40 (29%) of the 138 tested patients. The frequencies of the positive photopatch test reactions were sunscreens (57%), fragrances (18%), and antimicrobial agents (13%). Of the positive patch test responses, fragrances elicited 47% of the total positive reactions, followed by sunscreens (39%) and antimicrobial agents (7%). CONCLUSION: Polymorphous light eruption, chronic actinic dermatitis, and photoallergic contact dermatitis were the most frequently made diagnoses. Sunscreens, fragrances, and antimicrobial agents were the most common clinically relevant photoallergens and allergens.

Efficacy of ultraviolet B phototherapy for psoriasis in patients infected with human immunodeficiency virus.

To evaluate the efficacy of ultraviolet B (UVB) phototherapy for the treatment of psoriasis in patients infected with human immunodeficiency virus (HIV), the response of 14 patients was compared to that of matched seronegative control individuals. All patients were evaluated prior to treatment (baseline) and after 21 treatments for the extent of total body surface area (TBSA) involvement and the quantification of scale, erythema, and thickness of plaques using a scale of 0 (absent) to 4 (severe). The only concomitant medication allowed was salicylic acid in petrolatum. The cumulative score for scale, erythema, and thickness improved 1.9 +/- 0.5 [mean +/- standard error of mean (SEM)] in the HIV group and 2.4 +/- 0.3 in controls. There was 40.9 +/- 7.3% reduction of TBSA involvement in the former and 38.4 +/- 7.6% reduction in the latter group. None of the differences was statistically significant. There was no statistically significant difference in the response to therapy among various stages of immunosuppression in the HIV group. There was also no deterioration of immune status in this group. UVB phototherapy is an effective treatment for psoriasis in patients infected with HIV. The response is identical to that of matched control individuals.

Allergic reactions to tattoo pigment after laser treatment.

BACKGROUND: Cutaneous allergic reactions to pigments found in tattoos are not infrequent. Cinnabar (mercuric sulfide) is the most common cause of allergic reactions in tattoos and is probably related to a cell-mediated (delayed) hypersensitivity reaction. OBJECTIVE: The purpose of these case presentations is to describe a previously unreported complication of tattoo removal with two Q-switched lasers. RESULTS: Two patients without prior histories of skin disease experienced localized as well as widespread allergic reactions after treatment of their tattoos with two Q-switched lasers. CONCLUSION: The Q-switched ruby and neodymium:yttrium-aluminum-garnet lasers target intracellular tattoo pigment, causing rapid thermal expansion that fragments pigment-containing cells and causes the pigment to become extracellular. This extracellular pigment is then recognized by the immune system as foreign.

Skin response to ultraviolet B light in patients infected with human immunodeficiency virus.

Photosensitivity disorders have been reported in human immunodeficiency virus (HIV)-infected patients, often as the initial manifestation of the disease. The objective of this study was to evaluate whether the HIV-infected population demonstrates increased sensitivity to ultraviolet B (UVB) radiation. Minimal erythema dose values to UVB (MED-B) of 57 consecutive HIV-infected patients were compared to those of a control group of 57 consecutive patients with skin diseases, who were otherwise healthy and had no risk factors for HIV infection. MED-B determinations were performed in all individuals prior to the initiation of phototherapy for treatment of skin disease. None of the patients had a history of photosensitivity. Furthermore, the mean levels of the highest UVB doses received by each group during the treatment courses were compared. The mean age of the HIV-infected cohort was 43 years (range 26-61 years). The mean MED-B for this group was 82.8 +/- 3.8 (SEM) mJ/cm2. The mean age of the control group was 45 years (range 24-77 years), and their mean MED-B was 81.0 +/- 3.8 (SEM) mJ/cm2. After 12 weeks of treatment, one HIV-infected patient developed photosensitivity associated with a decreased MED-B value. The mean level of the highest UVB doses received by the HIV-infected group [427.5 +/- 67.2 (SEM) mJ/cm2] was lower than that received by the control group [640.8 +/- 65.9 (SEM) mJ/cm2], since HIV-infected patients received fewer treatments (mean: 34.7 treatments per patient) than the patients in the control group (mean: 65.6 treatments per patient). These data indicate that the HIV-infected patient population, without history of photosensitivity, does not show increased sensitivity to UVB light as determined by MED-B values.

Chronic actinic dermatitis. An analysis of 51 patients evaluated in the United States and Japan.

BACKGROUND AND DESIGN: We studied the clinical and photobiologic features of 51 patients with chronic actinic dermatitis who were evaluated at three institutions. The following criteria for patient selection were used: (1) a persistent eczematous eruption in the sun-exposed areas of greater than 3 months' duration; (2) decreased phototest results; and (3) when available, histologic changes of a dermal infiltrate of lymphocytes and macrophages, with or without epidermal spongiosis and atypical mononuclear cells in the dermis and epidermis. RESULTS: The 51 patients had a mean age of 62.7 years, a male-to-female ratio of 2.6:1, and a mean duration of eruption of 5.8 years. The most common abnormal results of the phototests were decreased minimal erythema doses to both UV-A and UV-B, followed by decreased minimal erythema doses to UV-A alone. Patients with abnormally low responses to UV-A or visible light and normal minimal erythema doses to UV-B had the same clinical profile as the overall patient population. Aside from protection from sunlight, treatment modalities that have been used include PUVA (8-methoxypsoralen and UV-A) photochemotherapy, azathioprine, hydroxychloroquine sulfate, and, for recalcitrant cases, cyclosporine. CONCLUSIONS: Chronic actinic dermatitis is a persistent photodermatosis associated with abnormal phototest responses to UV-A, and/or UV-B, and/or increased sensitivity to visible light; histopathologic changes are consistent with photodermatitis. Treatment consists of combinations of topical and oral medications.

Chronic actinic dermatitis. An immunohistochemical study of its T-cell antigenic profile, with comparison to cutaneous T-cell lymphoma.

Chronic actinic dermatitis (CAD) describes a persistent photosensitivity disorder in the absence of continued exposure to photosensitizers; it is characterized by a T-cell infiltrate within the epidermis and dermis. The purpose of this study was to characterize the T-cell infiltrate better immunohistochemically. Serial cryostat sections of fresh-frozen punch biopsy specimens of skin were analyzed in 11 patients with CAD and 3 patients with erythrodermic cutaneous T-cell lymphoma (CTCL). Monoclonal antibodies against the pan T-cell, pan B-cell, and T-cell subsets and the T cell-receptor (TCR) antigens were used. CD8-positive (T-suppressor-cytotoxic) cells were predominant in the epidermis of CAD, while CD4-positive (T-helper) cells were predominant in the epidermis and dermis of CTCL. CDw29-positive (T-memory) cells were predominant in all cases. The number of BF1 (beta-chain constant region of the TCR)-positive cells approximated the number of CD3-positive cells in all CAD cases but was significantly lower than the number of CD3-positive cells in two of three cases of CTCL. There was no clustering or preferential staining with any of the beta-chain variable-region antibodies in any of the specimens. These results indicate that CAD has a characteristic immunophenotype distinct from that of most cases of CTCL and that discordance between BF1 and CD3 expressions did not occur in the CAD cases.