A patient with psoriatic arthritis due to generalized pustular psoriasis (von Zumbusch type)

Pustular psoriasis is a rare skin disease that is observed in about 1% of all patients with psoriasis. We encounted a patient with psoriatic arthritis (PsA) due to pustular psoriasis. The patient was a 31-year old male. He visited our hospital due to generalized eruption and pain in multiple joints. Treatment was initiated under a diagnosis of psoriasis vulgaris and associated PsA. However, eruption extended to the entire body and became pustular, and fever developed. Since PsA symptoms were simultaneously aggravated, and body movements become difficult, he was admitted. A diagnosis of generalized pustular psoriasis (von Zumbusch) and associated symmetrical polyarthritis was made. Local therapy was performed. As systemic treatment, oral administration of an corticosteroid and weekly low-dose pulse methotrexate therapy were performed. The skin symptoms and PsA symptoms rapidly improved. At present, about one year after the initiation of treatment, the eruption almost completely disappeared, and joint pain does not present any problem in daily life.     

In-vitro photobactericidal activity of aminoacridines

We report four patients with severe erythrodermic, pustular psoriasis, or plaque-type psoriasis, who were treated with a combination of acitretin and bath PUVA. After 4 weeks out-patient treatment, the psoriasis in all patients had improved by > or = 90%. No patient had relapsed when reviewed at 3 months. No significant side-effects were seen with the combined retinoid/bath PUVA treatment. Acitretin and bath PUVA may be safely combined for the treatment of severe psoriasis.     

Exfoliatio areata linguae et mucosae oris: a mucous membrane manifestation of psoriasis pustulosa?

Lesions of the oral mucosa are frequently described in association with psoriasis, particularly in the pustular type. Controversy surrounds the question whether mucosal lesions can be considered as oral manifestation of psoriasis. Two patients presented with concurrent pustular psoriasis and mucosal lesions with the characteristic picture of geographic tongue. Histopathology of the mucosa showed typical features of psoriasis such as marked acanthosis, clubbing of the rete ridges, focal parakeratosis and neutrophilic infiltrates. There was parallel improvement of the skin and the mucosal lesions with systemic retinoid treatment. On the basis of the histopathological features and the clinical course we favour the hypothesis that geographic tongue is an oral manifestation of pustular psoriasis.     

Pustular vasculitis with clinical feature of pustular psoriasis and sternoclavicular hyperostosis

We report the case of a 51-year-old Japanese man with a unique pustulosis. He had multiple erythematous plaques and numerous pinpoint pustules on the trunk and extremities resembling pustular psoriasis. Histologic features revealed a fully developed intraepidermal abscess filled with neutrophils and disrupted epidermal keratinocytes. Mild leukocytosclastic vasculitis was seen in the underlying dermis. A direct immunofluorescence study revealed IgM, Clq, C3 and fibrinogen deposits in the dermal vessels. The patient had also sternoclavicular hyperostosis. We think that this represents a unique type of pustular vasculitis distinct from pustular psoriasis.     

Diet and breast cancer

A 78 year old women developed acute fingertip necrosis just a few days after starting dihydroergotamine. The lesions healed in 3 weeks after the medication was stopped. The patient had suffered from Raynaud syndrome for 5 years and limited systemic sclerosis was diagnosed during the necrotic episode. Advanced age and microangiopathies are contraindications to the use of ergot-containing preparations.     

Methotrexate for psoriasis

Methotrexate is an effective antipsoriatic agent and has been widely used to treat severe psoriasis since the 1960s. It is especially useful in acute generalized pustular psoriasis, psoriatic erythroderma, psoriatic arthritis and for extensive chronic plaque psoriasis in patients who are inadequately controlled by topical therapy alone. It has not, however, been formally compared with other systemic treatments for severe psoriasis such as cyclosporin, retinoids or photochemotherapy with psoralen and UVA (PUVA), but in comparison with these other therapies it is inexpensive, with correct use, its safety profile is favourable. In summary, therefore, it can be used as a short-term option to gain control of unstable psoriasis such as pustular psoriasis or erythroderma before returning to other modes of treatment, or more often, as long-term maintenance treatment. The most important potential side-effect is acute myelosuppression, which is the cause of most of the rare deaths attributable to this therapy for psoriasis. Myelosuppression is more likely in the elderly, in patients with renal impairment and/or folate depletion, and with overdose or drug interactions. Long-term therapy carries with it a risk of liver fibrosis which is related to the dosage regimen employed, and is increased by exposure to other hepatic toxins, particularly alcohol. The correlation between the risk of development of liver fibrosis, cumulative lifetime dose and duration of treatment with methotrexate is not clear-cut, but may have been overstated in some studies.     

Helix-coil transitions in DNA using a pH variation method: case of a melting paradox as a function of ionic strength

We describe a 31-year-old Japanese woman with generalized pustular psoriasis treated with PUVA who subsequently developed a bullous disease. Throughout the disease course, there was no phase of psoriasis vulgaris. Although several reports describe coexistence of psoriasis vulgaris and bullous disease such as bullous periphigoid, coexistence of generalized pustular psoriasis without any phase of psoriasis vulgaris and bullous disease is rare. As for the bullous disease, direct immunofluorescence study showed IgG and C3 deposition along the basement membrane zone. Indirect immunofluorescence disclosed IgG antibasement membrane zone antibodies. Indirect immunofluorescence on 1 mol/l sodium chloride-split skin demonstrated linear IgG staining almost exclusively on the dermal side of the split. Western immunoblot analysis revealed that the antibody was directed to neither epidermolysis bullosa acquisita antigen nor bullous pemphigoid antigens. Considering the unusual clinical course, we suspect the possibility of a novel autoimmune blistering disease.     

Treatment of refractory psoriasis with fluocinonide gel

Twenty patients with refractory psoriasis that had responded poorly to previous therapy were treated with fluocinonide gel (0.05 percent), unoccluded, for six weeks. Patients were evaluated weekly. By the sixth week, all patients had improved, and seventeen (85 percent) showed "excellent" improvement. One patient discontinued the trial after four weeks because the lesions had completely cleared. No other patient discontinued using the medication for any reason. Patient complaints were minimal and consisted of stinging (three patients), itching (two patients), and drying (two patients). The study suggests that fluocinonide gel (0.05 percent) is a cosmetically acceptable alternative for the treatment of refractory psoriasis.     

An atypical psoriatic spondylitis case, successfully treated with methotrexate

We present a 45-year-old male patient who was hospitalized with lumbar disc herniation and whose control magnetic resonance imaging (MRI) findings initially suggested brucella spondylitis. Definitive diagnosis, however, indicated psoriatic spondylitis and the patient was successfully treated with methotrexate. A diagnosis of lumbar disc herniation was made in May 1991, during his psoriasis vulgaris treatment. He was hospitalized in August 1994 with a complaint of low-back pain persisting over the last six months despite treatment with analgesics. He was evaluated by clinical, radiological, laboratory and scintigraphic methods, following control MRI findings suggesting infection of vertebral bodies, particularly pointing to brucellosis in addition to disc herniation. A diagnosis of psoriatic spondylitis was finally established and 7.5 mg methotrexate weekly was administered. Significant improvement was obtained of psoriatic skin lesions, low-back pain and MRI findings through a six-month treatment period.     

Highly purified omega-3-polyunsaturated fatty acids for topical treatment of psoriasis. Results of a double-blind, placebo-controlled multicentre study

We report the results of a multicentre, double-blind, placebo-controlled study of topical therapy with omega-3-polyunsaturated fatty acids (omega-3-PUFA) in 52 patients suffering from moderate plaque-type psoriasis. In each patient, two similar stable psoriatic plaques served as indicator lesions for the study. One indicator lesion was randomly assigned to treatment with topical preparations of highly purified omega-3-PUFA in one of two concentrations (1 or 10%), and the other was treated with placebo. Efficacy assessment was based on changes in local psoriasis severity index, area involved, erythema, desquamation, induration and pruritus. After 8 weeks of treatment, all indicator lesions had improved significantly, compared with baseline. However, no statistically or clinically relevant differences between the omega-3-PUFA-treated and the placebo-treated lesions were found. Therapy was well tolerated and, apart from one patient who developed perilesional eczema, no clinically relevant adverse events occurred. In conclusion, topical omega-3-PUFA were not effective in a randomized, placebo-controlled, double-blind setting. Results of non-blind trials should be (re-)considered with caution.     

Methotrexate hepatotoxicity

Hepatoxicity is a major adverse reaction that can occur during methotrexate treatment of the rheumatic diseases. The pathologic lesions are nonspecific and the pathogenesis is poorly understood. Early studies in psoriasis clearly established a relationship between hepatic injury and several risk factors, particularly alcohol use. Methotrexate hepatoxicity occurs less frequently in rheumatoid arthritis than previously reported in psoriasis patients. Consequently, the American College of Rheumatology guidelines for methotrexate monitoring do not recommend baseline and surveillance liver biopsies in low-risk patients. These guidelines seem to be useful and cost-effective.     

Transfer of autoimmune thyroiditis and resolution of palmoplantar pustular psoriasis following allogeneic bone marrow transplantation

We report an unusual case of a patient who was cured of one autoimmune disease (palmoplantar pustular psoriasis (PPP)) but developed another autoimmune disease (autoimmune thyroiditis) after allogeneic BMT. A 40-year-old man suffering from AML with PPP underwent allogeneic BMT from his HLA-identical sister for the treatment of AML. The patient experienced complete clearance of the cutaneous PPP despite the cessation of immunosuppressive therapy for over 2 years. However, he developed hyperthyroidism with anti-thyroglobulin antibodies 5 months after BMT, although he had showed normal thyroid functions without anti-thyroglobulin antibodies before BMT. The donor had no history of thyroid diseases and showed normal thyroid functions but was positive for anti-thyroglobulin antibodies. Thus, even when the donor is in a subclinical state, autoimmune thyroiditis may be transferred from donors to recipients by BMT.     

Effects of phototherapy on the production of cytokines by peripheral blood mononuclear cells and on systemic antibody responses in patients with psoriasis

Exposure to ultraviolet B (UVB) radiation results in the suppression of many cell-mediated immune responses, and recent studies mice and murine cells in vitro suggest a shift from a T-helper 1 (Th1) to a Th2 type of response on irradiation. Active psoriasis is considered to be a Th1-type disorder, chiefly on the basis of the cytokines produced by inflammatory cells in psoriatic lesions. We investigated the effect of phototherapy in patients with psoriasis on the cytokine profile of mitogen-stimulated mononuclear cells from peripheral blood and the concentration of IgG subclasses and IgE in the plasma. Eight patients were irradiated with a broad-band UV source (Sylvania UV6; 280-400 nm) three times a week and another eight with a narrow-band UVB source (Philips TL-01; 311-313 nm). Peripheral blood was collected before therapy started and after 1-4 weeks of therapy. Peripheral blood mononuclear cells were stimulated in vitro with phytohemagglutinin; proliferation was measured by incorporation of tritiated thymidine and culture supernatants assayed for interleukin (IL)-2, -4 and -10 and gamma-interferon (IFN) by enzyme-linked immunosorbent assays. Lymphoproliferation was not consistently affected by 4 weeks of UV6 therapy, and there was also no consistent change in the production of IL-2, IL-10 or gamma-IFN. In contrast, 4 weeks of TL-01 therapy significantly suppressed lymphoproliferative responses. In addition the production of IL-2, IL-10 and gamma-IFN was lowered after 1 week of TL-01 therapy, and this was even more apparent after the treatment had been extended to 4 weeks. IL-4 concentrations were below detectable levels in all the samples throughout the study. The amounts of IgG1, -2, -3 and -4 and IgE in the plasma of the patients did not vary with either of the two phototherapies. Thus, although no evidence was obtained to indicate that UV6 exposures affected T-helper subsets in psoriasis, TL-01 inhibited the activity of both Th1 and Th2 subsets while not altering plasma antibody concentrations.     

Findings on illiac joints after their replacement with total endoprothesis (author''s transl)

A 39 years old female patient with congenital erythroderma is reported. The condition was considered as the non bullous type of Brocq's congenital ichthyosiform erythroderma until recently. The patient was admitted as she had generalized erythema, desquamation and oedema, pyrexia and oliguria. The scales were fine and small, quite different from those of lamellar ichthyosis. The patient developed a recidivant pustular eruption on palms, face and trunk. So the diagnosis was changed to congenital psoriasiform erythroderma and this was supported by histopathological examination of both scaling and pustular lesions. There was a remarkable improvement on amethopterin therapy. The case is discussed and the relevant litterature is reviewed.     

Low sensitivity of adrenal chromaffin cells to acetylcholine, neostigmine and oxotremorine in 21-day-old rats

To evaluate the immunological function of peripheral blood monocytes (PBMC) in psoriasis, we measured spontaneous production of the inflammatory cytokines, TNF-alpha, IL-1beta and IL-6 from the PBMC of psoriasis patients, by enzyme linked immunosorbent assay (ELISA). The production of all three inflammatory cytokines by psoriatic PBMC was significantly higher than that by normal control PBMC. PBMC sampled from active psoriasis produced three cytokines significantly higher than samples from inactive psoriasis. In addition, IL-1beta and TNF-alpha production showed a positive relation to clinical severity, but IL-6 did not. TNF-alpha production increased much more than did the others. Therefore, the TNF-alpha to IL-1beta ratio was significantly higher, even in inactive psoriasis, than that of the normal control. In relation to focal infection, psoriatic PBMC sampled 3 h after a tonsillar provocation test increased cytokine production, compared with the level before provocation. The cases which responded to tonsillectomy or systemic methotrexate therapy, but not the non-responding cases, showed a significant decrease in PBMC cytokine productivity. These results strongly suggest that inflammatory cytokines, especially TNF-alpha, from monocytes are involved in the pathogenesis of psoriasis, and activated monocytes may work as an effective mediator of focal infection in skin lesions.     

Dermoid in the filum terminale of a newborn with myelomeningocele

Tumor necrosis factor-alpha (TNF-alpha) has been implicated as one of the critical mediators of psoriasis. Evidence for an important role on the progression of the disease is increasing, while recent clinical studies have suggested its beneficial role in the disease. Based on the results of our sequential analysis of the serum cytokine levels in a patient with pustular psoriasis, we speculate that immunologic effects of constitutive local release of TNF-alpha may be quite different from those of its systemic injection.     

CCAAT displacement protein (CDP/cut) binds a negative regulatory element in the human tryptophan hydroxylase gene

BACKGROUND: The pharmacokinetics of low-dose subcutaneous methotrexate have not been determined throughout the standard weekly dosing interval. It is not known whether methotrexate concentrations in the gastrointestinal tract are sufficient for pharmacologic activity in inflammatory bowel disease. METHODS: Ten patients with inflammatory bowel disease participated in the study. After the patients started taking 15 or 25 mg subcutaneous methotrexate once a week, erythrocyte methotrexate concentration was measured every 2 weeks. The absorption, rectal distribution, metabolism, and elimination of methotrexate were measured. The effect of methotrexate on proliferation of an intestinal epithelial cell line was determined. RESULTS: After weekly subcutaneous administration of methotrexate was begun, trough erythrocyte concentration rose to reach a plateau after 6 to 8 weeks, ranging from 150 to 300 nmol/L. More than 90% of subcutaneously administered methotrexate was rapidly excreted in the urine. The methotrexate plasma time course after subcutaneous administration fit a 2-compartment first-order model with biphasic elimination and trough concentration of about 1 nmol/L. Trough and peak methotrexate concentrations (mean value +/- SD) were 64 +/- 33 and 206 +/- 64 fmol/mg in the rectal mucosa and 4 +/- 3 and 51 +/- 26 nmol/L in the rectal lumen. These methotrexate concentrations were in the range found to be pharmacologically active against Caco-2 cell growth, that is, a 50% inhibitory concentration from 10 to 46 nmol/L. CONCLUSION: Subcutaneous methotrexate was well absorbed and distributed to the site of the lesions in patients with inflammatory bowel disease. Methotrexate was concentrated intracellularly in blood and in the rectum. The methotrexate concentration in the rectal mucosa remained within a pharmacologically active range throughout the dosing interval. The findings represent a pharmacologic explanation for the sustained efficacy of weekly methotrexate therapy.     

Narrowband UV-B produces superior clinical and histopathological resolution of moderate-to-severe psoriasis in patients compared with broadband UV-B

OBJECTIVE: To compare the therapeutic effectiveness of daily exposure to narrowband (NB) UV-B vs broadband (BB) UV-B with and without tar. DESIGN: Half-body exposures to NB UV-B or BB UV-B were given daily for 4 weeks in this comparative treatment study. Narrowband UV-B was delivered from TL-01 fluorescent bulbs and BB UV-B from conventional bulbs in the same phototherapy cabinet. Narrowband UV-B was compared using a paired treatment approach to BB UV-B above the waist and to BB UV-B with tar (Goeckerman treatment) below the waist. SETTING: General clinical research center of a university hospital inpatient unit. PATIENTS: Twenty-two patients with moderate-to-severe plaque-type psoriasis completed the study. MAIN OUTCOME MEASURES: Clinical efficacy was measured weekly using psoriasis severity scoring. Therapeutic outcomes after 4 weeks were compared in paired biopsy samples from treated lesions using objective histopathological measures (quantitative reduction in epidermal acanthosis and keratin 16 expression). RESULTS: Clinical resolution of psoriasis was achieved on 86% of paired sites treated with NB UV-B vs 73% treated with BB UV-B. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 88% of lesions treated with NB UV-B vs 59% treated with BB UV-B. Epidermal acanthosis was reduced more completely by NB UV-B treatment. Clinical resolution of psoriatic lesions occurred more rapidly following NB UV-B treatment, with some patients achieving complete resolution after 2 to 3 weeks of treatment. CONCLUSIONS: Narrowband UV-B offers a significant therapeutic advantage over BB UV-B in the treatment of psoriasis, with faster clearing and more complete disease resolution. The erythema response to NB UV-B treatment was significantly more intense and persistent compared with BB UV-B. Considerably more necrotic keratinocytes were observed in histopathological sections of skin treated with NB UV-B after a single 2.0-minimum erythema dose exposure. Treatment should be coupled with obligate minimum erythema dose testing to NB UV-B and close clinical observation during dose increases.     

Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis

BACKGROUND: The value of intensive combination therapy in early rheumatoid arthritis is unproven. In a multicentre, double-blind, randomised trial (COBRA), we compared the combination of sulphasalazine (2 g/day), methotrexate (7.5 mg/week), and prednisolone (initially 60 mg/day, tapered in 6 weekly steps to 7.5 mg/day) with sulphasalazine alone. METHODS: 155 patients with early rheumatoid arthritis (median duration 4 months) were randomly assigned combined treatment (76) or sulphasalazine alone (79). Prednisolone and methotrexate were tapered and stopped after 28 and 40 weeks, respectively. The main outcomes were the pooled index (a weighted change score of five disease activity measures) and the Sharp/Van der Heijde radiographic damage score in hands and feet. Independent health-care professionals assessed the main outcomes without knowledge of treatment allocation. FINDINGS: At week 28, the mean pooled index was 1.4 (95% CI 1.2-1.6) in the combined treatment group and 0.8 (0.6-1.0) in the sulphasalazine group (p < 0.0001). At this time, 55 (72%) and 39 (49%) patients, respectively, were improved according to American College of Rheumatology criteria. The clinical difference between the groups decreased and was no longer significant after prednisolone was stopped, and there were no further changes after methotrexate was stopped. At 28 weeks, the radiographic damage score had increased by a median of 1 (range 0-28) in the combined-therapy group and 4 (0-44) in the sulphasalazine group (p < 0.0001). The increases at week 56 (2 [0-43] vs 6 [0-54], p = 0.004), and at week 80 (4 [0-80] vs 12 [0-72], p = 0.01) were also significant. Further analysis suggests that combined therapy immediately suppressed damage progression, whereas sulphasalazine did so less effectively and with a lag of 6 to 12 months. There were fewer withdrawals in the combined therapy than the sulphasalazine group (6 [8%] vs 23 [29%]), and they occurred later. INTERPRETATION: This combined-therapy regimen offers additional disease control over and above that of sulphasalazine alone that persists for up to a year after corticosteroids are stopped. Although confirmatory studies and long-term follow-up are needed, this approach may prove useful in the treatment of early rheumatoid arthritis.     

Pyogenic granuloma-like lesions in a patient using topical tretinoin

A 16-year-old male developed numerous pyogenic granuloma like-lesions across his neck, chest and back after 6 weeks isotretinoin therapy for cystic acne. The isotretinoin was ceased and he was commenced on oral steroids. After 6 weeks, the lesions were almost completely healed. However, due to worsening comedonal acne, the patient was commenced on topical tretinoin cream 0.05% twice daily to his chest. He was reviewed 2 weeks later and, surprisingly, 2 new pyogenic granuloma-like lesions had developed on his chest. These lesions persisted until the topical tretinoin was ceased 3 months later.