T. Krieg

Anti-CD20 monoclonal antibody (rituximab) in the treatment of pemphigus.

Backgroundu2002 Pemphigus is a severe autoimmune blistering disorder caused by autoantibodies to desmoglein 1 and 3. The disease course is typically severe, thus requiring multiple immunosuppressive agents. The treatment is still challenging and in some patients with recalcitrant disease, therapies fail and therapeutic options are limited.

Expanding the keratin mutation database: novel and recurrent mutations and genotype–phenotype correlations in 28 patients with epidermolytic ichthyosis

Backgroundu2002 Epidermolytic ichthyosis (EI) is a hereditary keratinization disorder caused by mutations in the keratin 1 (KRT1) or keratin 10 (KRT10) genes. In most cases of severe EI, heterozygous single point mutations are found at the highly conserved helix boundary motifs of KRT1 and KRT10 that play a critical role in filament formation. The presence of palmoplantar keratoderma suggests KRT1 mutations, whereas KRT10 mutations in most instances give rise to the nonpalmoplantar variants.

Pseudoscleroderma associated with lung cancer: correlation of collagen type I and connective tissue growth factor gene expression

Pseudoscleroderma as a paraneoplastic syndrome is a rare disease. We report here a patient with lung cancer (undifferentiated squamous cell carcinoma), who developed acrosclerosis. Using in situ hybridization, marked expression of α1(I)‐collagen and connective tissue growth factor (CTGF) mRNA was found in fibroblasts scattered throughout the dermis. However, transforming growth factor (TGF)‐β1 expression was not detected. The pattern of CTGF gene expression and collagen synthesis was similar to that in systemic scleroderma. The absence of TGF‐β1 mRNA could indicate that tumour‐derived factors induce the expression of CTGF.

Identification of novel and known KRT5 and KRT14 mutations in 53 patients with epidermolysis bullosa simplex: correlation between genotype and phenotype

Backgroundu2002 Basal epidermolysis bullosa simplex (EBS) is a hereditary skin blistering disorder resulting in most cases from missense mutations in the keratin 5 (KRT5) or keratin 14 (KRT14) genes.

Acquired perforating collagenosis: is it due to damage by scratching?

Sir, Sea-urchins are found along the coastline, including in many tourism sites. Their spines consist of calcium carbonate crystals covered by a layer of epithelium. Injuries from seaurchins result from penetration of the spines into the dermis or subcutis, leading to pain of several days duration. Complications include local inflammation and infection or a delayed granulomatous foreign-body reaction that can develop weeks or months later. The latter may often be followed by long-lasting pain and even by loss of function. To prevent these sequelae, most authors favour the excision of spines rather than waiting for spontaneous recovery as recommended by others. At present, no uniformly accepted successful treatment method is available. We found the erbium:YAG laser to be a suitable tool for effective removal of the spines. Four patients presented to our outpatient department about 1 week after a sea-urchin spinous injury during a vacation. They all suffered from severe pain and loss of function of the injured extremities. Previous attempts to remove the spines mechanically had not been successful. Inspection disclosed multiple black spines (. 50) up to 1 mm in diameter in the soles of the feet (Fig. 1A) in three of the patients. Mobility at the distal interphalangeal joints was reduced due to an accompanying erythematous oedema. The fourth patient had spines in the left index finger, with swelling and reduced flexibility. We decided to use the erbium:YAG laser (Medilas E, Dornier, Munich, Germany; spot size 2 ́5 mm, 300 mJ, fluence 6 J cm, repetition rate 5±10 Hz) to remove the foreign material. Three of the patients were treated under local infiltration anaesthesia (1% lidocaine without epinephrine), and one under general anaesthesia. The foreign bodies were destroyed leaving circumscribed crater lesions with tiny pinpoint areas of bleeding (Fig. 1B). Postoperatively, an antiseptic wound dressing was applied. In two of the patients we took a 2-mm skin biopsy; histological examination revealed penetration of the spines into the deep dermis and even subcutis. Two treatment sessions were necessary to remove all the widespread spines in two patients. The wounds re-epithelialized at the latest within 2 weeks after treatment; in some locations we saw focal hyperkeratosis but there were no signs of scarring. Figure 1(C) shows the typical appearance 4 weeks after treatment. Mobility and function of the distal phalanges were restored completely. During 1 year of follow-up no delayed granulomatous foreign-body reactions or other complications have been observed. Sea-urchins are relatively sedentary creatures often attached to rocks or corals. The porous spines penetrate the skin when stepped on. Mechanical extraction is almost ineffective because the spines fragment easily; surgical excision has been recommended, even though this is difficult with widespread injuries. Leaving spines in place leads to acute pain, local inflammation or infections and a risk of delayed granulomatous foreign-body reactions. There are reports of granulomatous inflammation in the dermis and subcutaneous tissues, with severe involvement of bone and cartilaginous surfaces followed by chronic pain and even loss of function.

Bullous Pemphigoid in a Patient Treated with UVA-1 Phototherapy for Disseminated Morphea

Bullous pemphigoid is an autoimmune disease of the skin characterized by the production of antibodies directed at structures of the basement membrane zone (BMZ) leading to subepidermal blisters. Several causative triggers have been described in the literature, among them UV light. Here, we report on a 73-year-old Caucasian female with disseminated morphea who developed blisters on her extremities after receiving whole-body UVA-1 phototherapy. The initial differential diagnosis of a phototoxic versus photoallergic reaction was ruled out as the lesions continued to spread after discontinuation of phototherapy. Histological and direct immunofluorescence examination showing a subepidermal blister and linear IgG deposits along the BMZ along with detection of circulating anti-BMZ antibodies led to the diagnosis of bullous pemphigoid. Immunosuppressive therapy resulted in regression of all blisters. After ruling out other possible causes, such as neoplasias or drugs, we conclude that UVA-1 has to be regarded as the most likely trigger of the disease.

Increased deposition of fibulin-2 in solar elastosis and its colocalization with elastic fibres

Backgroundu2003Fibulin‐2 is a 195‐kDa protein belonging to a novel family of extracellular matrix proteins that might be involved in microfibril and elastic fibre organization.

Immediate Reaction to Roxithromycin and Prick Test Cross-Sensitization to Erythromycin and Clarithromycin

Allergic reactions to macrolides appear to be very rare. Only a few cases of fixed drug eruption or urticaria due to the administration of erythromycin have been reported. Cross-reactions between the different macrolides have not yet been published. We report a case of a 31-year-old female patient who developed generalized urticaria and tachycardia shortly after administration of roxithromycin (Rulid®). Immediate-type hypersensitivity was confirmed by positive prick test reactions to roxithromycin and the chemically closely related macrolides erythromycin and clarithromycin.

Chronic graft-versus-host disease with skin signs suggestive of dermatomyositis.

1 Wu JK, Siller G, Strutton G. Psoriasis induced by topical imiquimod. Aust J Dermatol 2004; 45: 47–50. 2 Dummer R, Urosevic M, Kempf W, Hoek K, Hafner J, Burg G. Imiquimod in basal cell carcinoma: how does it work? Br J Dermatol 2003; 149 (Suppl. 66): 57–8. 3 Gilleiet M, Conrad C, Geiges M et al. Psoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors. Arch Dermatol 2004; 140: 1490–5. 4 Funk J, Langeland T, Schrumph E, Hanssen LE. Psoriasis induced by interferon-alpha. Br J Dermatol 1991; 125: 463–5. 5 3M Pharmaceuticals. Study 1253-IMIQ. Data on file.

Successful treatment of refractory rheumatoid arthritis-associated leg ulcerations with adalimumab

SIR, The development of recalcitrant skin ulcerations is a severe complication of rheumatoid arthritis (RA). About 10% of patients with RA will develop painful, therapy-resistant ulcerations of the lower leg. The aetiology of leg ulcers in RA is unclear and clinical studies indicate that most are of multifactorial origin. Contributing factors include venous insufficiency, peripheral arterial disease and ⁄or mechanical factors; the role of vasculitis in leg ulceration in RA is controversial. Pyoderma gangrenosum (PG) may occur in association with RA. Leg ulcers in RA tend to be resistant to local therapy; treatment often includes the stabilization of the underlying autoimmune disease, e.g. with high doses of glucocorticoids or other potent immunosuppressives. In recent years, excessive tumour necrosis factor (TNF)-a production has been shown to play a pivotal role in the pathogenesis of RA, and blocking TNF-a signalling has opened a possible perspective for controlling synovial inflammation and destruction of articular cartilage and bone. However, little is known about the effect on cutaneous manifestations of RA of this treatment, specifically on healing of leg ulcerations. We report a 36-year-old woman who presented with a 10-year history of severe seronegative RA. Examination revealed deformities, impaired mobility and severe pain in both forefeet, ankles, knees and hips. Previous RA therapies included nonsteroidal anti-inflammatory and disease-modifying antirheumatic drugs, a synovectomy of both knee joints, a total left hip replacement and several chemical and radioactive treatments to the synovia of the affected joints. At presentation to our clinic treatment included prednisolone 10 mg daily, methotrexate 20 mg weekly, naproxen and morphine 360 mg daily. During the previous 2 months multiple cutaneous ulcerations had occurred following minor skin injury on both lower legs in various locations and on the back of both feet; the largest ulceration (8 · 12 cm) was present on the medial proximal aspect of the lower left leg, and tendon and bone were exposed (Fig. 1A). Previous medical history included mild hypothyroidism and steroid-induced osteoporosis. Laboratory investigations showed persistent mild anaemia, thrombocytosis, elevated erythrocyte sedimentation rate and C-reactive protein, and slightly increased antinuclear antibodies; rheumatoid factor, cytoplasmic and perinuclear immunofluorescent pattern antineutrophil cytoplasmic antibodies, anti-ss ⁄dsDNA antibodies, C3 ⁄C4, electrolytes, coagulation parameters, and kidney and liver function tests were within normal limits. Bone scintigraphy showed increased activity in various joints. There was no sign of arterial disease (anklebrachial pressure index 1Æ2) or venous insufficiency (normal duplex ultrasound). Based on these data, the clinical appearance of the ulcerations, and accompanying increased systemic inflammation parameters, the ulcerations were most likely to be vasculitic in nature. Although we could not completely rule out the diagnosis of RA-associated PG, this diagnosis was unlikely because the clinical appearance was different, the rest of the skin showed no ulcerations, and wound healing was normal following trauma or surgery. Treatment was started with cyclophosphamide pulse therapy, in addition to prednisolone 10 mg daily and methotrexate Fig 1. (A) Deep, painful ulcer on the lower left leg before adalimumab treatment. (B) The same lesion after 6 months of adalimumab treatment.