Study of T helper 1 and T helper 2 responses in pemphigus vulgaris patients receiving interferon alpha 2a injections in addition to a standard protocol therapy: a randomized controlled trial.

T helper (Th)1 insufficiency was recently found to be related to the pathogenesis of pemphigus vulgaris (PV). Decreased Th1 response was particularly noticed in the early stages of PV. Therefore, administration of interferon alpha in the early stages of aggressive PV may lead to rapid control of the acute stage of the disease. Our aim was to evaluate the role of interferon alpha in the treatment of PV. 30 patients with acute severe PV (>60 % affection) and 30 age and sex-matched healthy subjects were included in this RCT. Patients were randomly divided into two groups (A and B). Group B patients received interferon retard (one subcutaneous injection/week for 4 weeks) in addition to our protocol for the treatment of PV (systemic pulse corticosteroids/cyclophosphamide in combination with sulphasalazine and pentoxifylline) that was administered to all the included patients. IFN-γ and IL-4 were estimated by ELISA before treatment, after 4 weeks and at the end of the study duration (12 weeks). Clinical assessment was done by PAAS on a biweekly basis. All PV patients showed significantly (P < 0.001) elevated levels of IL-4 and significantly (P < 0.001) depressed mean concentration of IFN-γ as compared with healthy controls. Twelve weeks after therapy both groups showed significant improvement in their mean PAAS being more evident and more rapid in group B. IFN-γ was elevated significantly and IL-4 was dropped significantly in group B patients in comparison to group A (P < 0.001). As a conclusion, interferon therapy in severe PV could achieve a more prompt and better clinical response.

Study of T helper (17) and T regulatory cells in psoriatic patients receiving live attenuated varicella vaccine therapy in a randomized controlled trial.

BACKGROUND: The use of live attenuated varicella vaccine (Varilrix(®)) as an adjuvant treatment in severe cases of psoriasis has recently been postulated. Its efficacy raised questions regarding its possible mechanisms of action. OBJECTIVE: To compare the efficacy and safety of combining Varilrix(®) and cyclosporine to cyclosporine alone in the treatment of severe psoriasis. Furthermore, to study the expression of T helper (Th)17 and T regulatory (Tregs) cells before and after therapy. MATERIALS AND METHODS: This randomized controlled trial included 24 psoriatic patients, randomly divided into 2 groups (A and B). All patients received cyclosporine at a daily dose of 2.5 mg/kg/day. In addition, group A received 4 doses of Varilrix(®) once/3 weeks, and group B received 4 doses of subcutaneous saline. Skin biopsies were obtained from all patients before and after therapy and from all controls for estimation of interleukin (IL)-17, IL-22 and Forkhead boxP3 (FoxP3) using RT-PCR. RESULTS: Group A patients showed a significantly higher % of clinical improvement (P = 0.011), which occurred earlier than group B. At baseline, levels of IL-17 and IL-22 were significantly higher while the level of FoxP3 was significantly lower in patients (P<0.001) compared to controls. After therapy, both groups showed significant reductions in both IL-17 and IL-22 levels, and significant elevation in FoxP3 (P<0.001). This change was significantly more evident in group A patients. CONCLUSION: Live attenuated varicella vaccine could play a role in the treatment of psoriasis when combined with low dose cyclosporine through accentuating the influence on the Th17/Treg balance.

Mycophenolate mofetil: a novel immunosuppressant in the treatment of dystrophic epidermolysis bullosa, a randomized controlled trial.

BACKGROUND: No effective treatment has been found for epidermolysis bullosa dystrophica (EBD). OBJECTIVE: To evaluate the efficacy and safety mycophenolate mofetil (MMF) in treating EBD. METHODS: This randomized controlled double-blinded study included 35 patients with severe generalized EBD. Patients were randomly divided into two groups: group I (18 patients) received cyclosporine therapy (5 mg/kg/day) and group II (17 patients) received MMF therapy (500-1500 mg/day). Clinical assessment was made weekly for 3 months from the start of the treatment. Patients were assessed by measuring the extent of the disease, the % of improvement, assessing the number of new blister formation and the time of complete healing of new blisters. Side effects were recorded when detected. RESULTS: The % of improvement in the disease extent was statistically significantly higher (p = 0.009) in group I (mean ± SD: 59.21 ± 22.676) than in group II (mean ± SD: 44.03 ± 25.71). As regards the number of new blisters and the rate of healing of blisters, there was no statistically significant difference between both groups (p = 0.693 and 0.404, respectively). No serious side effects were reported. CONCLUSION: MMF seems to be a good therapeutic option for the long-term treatment of EBD, it can be a good alternative for patients who cannot tolerate cyclosporine.

Hypopigmented parapsoriasis en plaque, a new, overlooked member of the parapsoriasis family: a report of 34 patients and a 7-year experience.

BACKGROUND: In the past 7 years we have extensively studied an uncommon hypopigmented disorder that, apart from hypopigmentation, showed many common features with parapsoriasis en plaque (PSEP), both clinically and histopathologically. OBJECTIVE: We sought to verify whether this disorder should be considered a hypopigmented variant of PSEP and thus be referred to as hypopigmented PSEP. METHODS: A total of 34 patients presenting with this peculiar hypopigmented disorder were included (2003-2010). Patients were subjected to a predesigned algorithm excluding all possible differential diagnoses of hypopigmented lesions. RESULTS: Our findings indicated that this disorder can be diagnosed as hypopigmented PSEP. These findings included: (1) exclusion of all other disorders causing similar hypopigmented lesions; (2) shape and size of the lesions being very similar to those of classic small PSEP (small-plaque parapsoriasis [SPP]); (3) similar distribution of the lesions (trunk, proximal upper and lower limbs) to the classic PSEP; (4) digitiform extensions of most the lesions (70.5% of our patients) as in SPP; (5) absence of itching as in PSEP (SPP type); (6) good response to narrowband ultraviolet B in 76.4% of the patients (n = 26); and (7) during follow-up 5 patients (14.7%) converted into hypopigmentd mycosis fungoides. LIMITATIONS: A limitation in our study is that we did not perform clonal T-cell receptor gene rearrangement because of limited resources. CONCLUSION: Based on our findings we believe that this hypopigmented disorder is a well-defined new variant of the PSEP family that shows, apart from the hypopigmentation, all the features of PSEP, particularly the SPP variant, and accordingly could be referred to as hypopigmented PSEP.

Comparative study of the effect of a daily steroid regimen versus a weekly oral pulse steroid regimen on morphological changes, blood sugar, bone mineral density and suprarenal gland activity.

BACKGROUND: The most serious side effects of systemic steroids include osteoporosis and suprarenal suppression. Many steroid regimens have been suggested to minimize these side effects; one of them is oral steroid pulse therapy. OBJECTIVE: To compare the side effects of a daily oral steroid regimen versus a weekly oral steroid pulse regimen on bone mineral density and suprarenal suppression. METHODS: Thirty patients with different skin diseases were divided into two groups: 15 for oral daily steroids (ODS) (group 1) and 15 for weekly oral pulse steroids (WOPS) (group 2). They were evaluated for bone mineral density (measured by DEXA) and suprarenal suppression (measured by serum cortisol level), morphological changes and blood sugar. Treatment was continued for 6 months to 3 years. RESULTS: Cushingoid features in group 1 were observed in 73%, yet they were not detectable in group 2. Disturbed blood sugar in group 1 was 33% and 0% in group 2. The serum cortisol level was lower in patients on ODS than those on WOPS. The effect of WOPS on bone mineral density was very limited in comparison with the ODS. CONCLUSION: Weekly oral steroid pulse therapy induces no significant bone loss and no suprarenal suppression and can be an alternative option in the treatment of chronic disorders requiring long-term oral steroid therapy.

Leukocytoclastic vasculitis and necrolytic acral erythema in patients with hepatitis C infection: do viral load and viral genotype play a role?

BACKGROUND: Leukocytoclastic vasculitis (LCV) and necrolytic acral erythema (NAE) are skin disorders associated with hepatitis C virus (HCV) infection. However, they have not been found to occur simultaneously in the same patient. OBJECTIVE: We sought to analyze the role of serum HCV-RNA levels and HCV genotype in the pathogenesis of both LCV and NAE in an attempt to assess whether these two parameters play a role in mutual exclusivity of LCV and NAE in the same patient. METHODS: The study included 11 patients with LCV and 13 with NAE, all of whom were infected with HCV. All 24 patients were evaluated for the quantitative levels of HCV-RNA, using real-time polymerase chain reaction. HCV genotyping was performed on 10 patients in each group (N = 20). RESULTS: Patients with LCV had a higher prevalence of moderate and high levels of HCV-RNA viremia (P = .038) than those with NAE. However, there was no significant difference in HCV genotype between LCV and NAE groups (P = .211). LIMITATIONS: Small number of cases is a limitation. CONCLUSION: Viral load seems to play a role in determining the response of the skin to HCV infection. High levels of HCV viremia were found to be significantly associated with LCV but not with NAE. HCV viremia may play a role in the development of LCV in HCV-infected patients.

Microscopic study of normal skin in cases of mycosis fungoides.

BACKGROUND: During therapy of patients with mycosis fungoides (MF) at the Department of Dermatology, Kasr El-Aini Hospital, follow-up biopsies are routinely taken every 2 months. It was noticed that lesions of MF might become clinically normal during treatment, and yet still show microscopical evidence of MF. This finding raised the possibility that clinically normal skin in MF could be microscopically involved. AIM: The aim of our work was to evaluate the degree of histopathological involvement of normal-looking skin in patients with MF. PATIENTS AND METHODS: Thirty patients with stage IB were biopsied from their normal skin. Two biopsies were taken: one proximal (2 cm) and the other distal (> 5 cm) from any visible lesion. Ten normal controls were included in the study. All specimens were stained with H&E and examined microscopically. The microscopical diagnosis was confirmed by immunophenotyping. RESULTS: Epidermotropism was detected in 21 (70%) of the proximal skin biopsies and 14 (47%) of the distal skin biopsies, whereas no biopsy from the control group showed epidermotropism. All the proximal skin biopsies showed dermal infiltrate and 90% of the biopsies from the distal normal skin showed dermal infiltrate (mostly superficial perivascular). CONCLUSION: Normal skin in patients with MF could be affected microscopically and this may raise questions regarding the credibility of the current staging classification of MF, and may necessitate taking biopsies from normal skin before starting topical treatment. During MF treatment, biopsies from cured lesions are required before starting withdrawal.

Muckle-Wells syndrome: report of six cases with hyperpigmented sclerodermoid skin lesions.

Muckle-Wells syndrome (MWS) is a rare syndrome, characterized by chronic recurrent urticaria, often combined with fever, chills, rigors, malaise, and arthralgia. Progressive sensorineural deafness, and, in approximately one third of the patients, amyloidosis of the kidneys as well as of other organs may occur. It was first described in 1962 by Muckle and Wells. Herein we describe six cases of MWS showing, in addition to the classic features of MWS, unique skin lesions that to the best of our knowledge have not been described before in association with MWS.

Histopathological study of apparently normal skin of patients with leprosy.

BACKGROUND: Several clinical and laboratory observations point to the possible microscopical affection of normal-looking skin in leprosy. OBJECTIVE: This study was carried out to verify the microscopical affection of apparently normal-looking skin in different types of leprosy. PATIENTS AND METHODS: The study included 50 patients with different clinical types of leprosy. Biopsies from both skin lesions and normal-looking skin were obtained from each patient and examined for microscopical evidence of leprosy. RESULTS: Microscopical affection of normal-looking skin was detected in 52% of our cases, with higher incidence of affection towards the lepromatous end of the disease. CONCLUSION: Our findings underscore that the incidence of microscopical affection of normal-looking skin in leprosy is much higher on the lepromatous end of the spectrum of leprosy than on the tuberculoid end; during treatment, the leprosy granulomas may disappear from the normal skin before the clinical lesions. Moreover, the microscopic picture of indeterminate leprosy can be observed in the normal-looking skin of patients with tuberculoid leprosy or lepromatous leprosy, and this description appears not to be confined to the entity known as indeterminate leprosy.

Vitiligo vs. hypopigmented mycosis fungoides (histopathological and immunohistochemical study, univariate analysis).

Vitiligo is a common skin disease characterized by the presence of well circumscribed, depigmented milky white macules devoid of identifiable melanocytes. On the other hand, hypopigmented mycosis fungoides (MF) is a rare variant of MF which presents clinically as persistent hypopigmented macules and patches. Both disorders show a predominance of CD8+ T cells in tissue samples and hence the differentiation between the two diseases on clinical, histopathological and even immunohistochemical grounds may offer great difficulty. The aim of this work is to identity certain histopathological clues which might help to differentiate between the two diseases. The study included 54 patients (26 vitiligo patients and 28 patients with Hypopigmented MF). Skin biopsies were taken and examined by hematoxylin and eosin and CD3, CD4 and CD8 markers were performed for ten vitiligo and nine MF patients. We have found that epidermotropism, hydropic degeneration of basal cells, partial loss of pigment, preservation of some melanocytes, presence of lymphocytes within the papillary dermis, increased density of the dermal infiltrate and wiry fibrosis of the papillary dermal collagen were detected with a significantly higher incidence in hypopigmented MF rather than vitiligo (P-values < 0.0001, < 0.00011, < 0.00011, = 0.001, = 0.008 and = 0.001 respectively). On the other hand, focal thickening of the basement membrane, complete loss of pigmentation, total absence of melanocytes, as well as absence or sparsness of lymphocytes in the dermal papillae were seen much more frequently in vitiligo. Statistical analysis of these differences was significant with P-values < 0.00011, < 0.00011, < 0.00011, = 0.008 respectively, regarding these pathological criteria. We conclude that differentiation of hypopigmented MF from vitiligo is possible by relying on the histopathological clues described in this study. This is particularly useful in areas of the world where cost benefit is crucial.

Branchio-oculo-facial syndrome with bilateral linear scars of the neck.

A case of branchio-oculo-facial syndrome with bilateral linear scars affecting both sides of the neck is described. The disease occured in a male patient aged 20 years and presented with facial asymmetry, pre and postauricular pits, lip pits, microphthalmia, broad malformed nose, colobomas and dystrophic right kidney. In addition, there were bilateral linear hypertrophic scars on both sides of the neck. We believe that the latter lesions may represent the end stage of dermal thymus; a rare condition which has been reported so far in only four cases, two of which had branchio-oculo-facial syndrome.

Basaloid follicular hamartoma.

Basaloid follicular hamartoma (BFH) is a unique benign follicular hamartoma characterized by variable clinical presentations, identical histologic features and possible associations with numerous disorders. Basaloid follicular hamartoma may be hereditary or acquired. Hereditary cases may be either generalized or unilateral nevoid. Although the generalized forms are usually associated with systemic manifestations, such as myasthenia gravis,(2) it may occasionally present without internal disorders. On the other hand, the acquired forms of BFH may present in the form of localized or solitary forms. Herein we present four cases of BFH, one of them (first case) represents a unique form of the generalized variant of BFH, showing no associated internal disorders.

Familial gigantic melanocytosis.

BACKGROUND: Familial gigantic melanocytosis (FGM) is a rare disorder first described in 1984 and termed "familial melanopathy with gigantic melanocytes". The cause of the disorder is still unknown. Melanocytes in both hyper- and hypopigmented skin seem to be unable to deliver melanin to the surrounding keratinocytes. OBJECTIVE: In this study, we report four new cases of FGM. Electron microscopic examination was performed in a trial to shed more light on the underlying defect in this disorder. PATIENTS AND METHODS: Patients were examined clinically and biopsies were taken from both hyperpigmented and hypopigmented areas, and divided into two parts; one part was processed for routine microscopic examination with hematoxylin and eosin and Masson Fontana stains. The other portion of the biopsy was fixed in glutraldhyde 3% and processed for electron microscopic (EM) examination. RESULTS: By light microscopy, the patients' skin showed areas of hyperpigmented basal cells alternating with poorly pigmented areas. Hair follicles in the scalp biopsies showed the same pathology. By EM, pigmented areas showed gigantic melanocytes and heavily pigmented keratinocytes. Nonpigmented areas showed poorly pigmented keratinocytes and fewer, but also gigantic melanocytes. CONCLUSIONS: The raindrop-like hypopigmentation in this disorder can be explained by a failure of melanocytes to deliver melanin to their surrounding keratinocytes. The cause of the presence of heavily pigmented keratinocytes in the hyperpigmented zones could not be determined. There is a strong possibility of a more widespread abnormality affecting not just the melanocytes.