Cutaneous ulcerations on hands and heels secondary to long-term hydroxyurea treatment

Hydroxyurea is a chemotherapeutic agent used to treat myeloproliferative disorders and other non-neoplastic conditions. Cutaneous side-effects have been described in long-term therapy with hydroxyurea and include xerosis, hyperpigmentation, skin atrophy, erythema, alopecia, skin tumours and ulceration of the skin, particularly of the legs. We present a 71-year old patient with chronic myelocytic leukemia (CML) who developed extremely painful ulcers on the hands and heels as well as skin tumours while on long-term therapy with hydroxyurea. The ulcers were resistant to therapy but healed three months after discontinuation of hydroxyurea therapy.     

Acral keratoses and leucocytoclastic vasculitis occurring during treatment of essential thrombocythaemia with hydroxyurea

Hydroxyurea is used in essential thrombocythaemia to lower thromboembolic risk. Cutaneous adverse effects from hydroxyurea are diverse. Small vessel vasculitis has been rarely reported, and the coexistence of several different morphologies has not been described. We report a case of acral keratoses, psoriasiform plaques and leucocytoclastic vasculitis (LCV) in a patient with essential thrombocythaemia. A 69‐year‐old woman developed a confusing array of skin lesions including keratotic papules, psoriasiform plaques and keratoderma 4 years after commencing hydroxyurea therapy. The initial diagnosis was hand and foot psoriasis, but lesions were resistant to therapy. With an increase in the dose of hydroxyurea, the lesions ulcerated. Skin biopsies taken from different sites indicated different diagnoses, including LCV. Discontinuation of hydroxyurea yielded rapid improvement. Although the most commonly reported cutaneous adverse effect from hydroxyurea is leg ulceration, this can be preceded or accompanied by less dramatic skin lesions. Unless recognized, delayed diagnosis and lesion progression can occur.     

Bluefarb-Stewart syndrome--report of a new case

Cutaneous lesions resembling Kaposi's sarcoma may develop on legs and feet of patients with acral arteriovenous malformation. A case of this rare syndrome is reported and the main features of the 17 published cases are summarized in a table.     

Leg ulcer in a patient associated with hydroxyurea therapy

Hydroxyurea is a hydroxylated derivate of urea commonly used in the treatment of various hematologic disorders. Cutaneous side-effects such as alopecia, diffuse hyperpigmentation, scaling, poikiloderma, atrophy of the skin and subcutaneous tissues or nail changes can develop after long-term treatment with hydroxyurea. Painful leg ulcers in association with hydroxyurea have only rarely been reported. We present a report of a 52-year-old patient with essential thrombocythemia suffering from painful leg ulcers 3 years after starting therapy with hydroxyurea. We decided to treat the leg ulcers following a modern phase-adapted wound-healing strategy and continued hydroxyurea therapy until complete healing of the ulcers. In conclusion, cutaneous ulceration of the leg is one adverse effect in patients with essential thrombocythemia during hydroxyurea therapy. Healing does not necessarily require discontinuation of the drug. Therefore, therapists should first optimize a conservative and systematic wound-healing strategy. If these interventions fail, discontinuation of hydroxyurea therapy is advisable.     

Efficacy of combined radiotherapy and anti‐programmed death 1 therapy in acral and mucosal melanoma

Some studies showed that clinical response to immune check point inhibitors is lower in acral and mucosal melanoma than in cutaneous melanoma. Although the synergistic effect of radiotherapy (RT) and ipilimumab has been reported in patients with brain metastasis, the efficacy of combined RT and anti‐programmed death 1 (PD‐1) therapy for acral and mucosal melanoma is unclear. The present study aimed to evaluate the efficacy of combined RT and anti‐PD‐1 therapy for acral and mucosal melanoma. We retrospectively analyzed patients with acral or mucosal melanoma who were treated with anti‐PD‐1 and RT at Sapporo Medical University Hospital. In 10 patients (acral, 3; mucosal, 7), the response rate (RR) and the disease control rate (DCR) were 40% and 60%, respectively. As regards mucosal melanoma, four of the seven patients had achieved complete response + partial response, and three had progressive disease (RR = 57.1%). Meanwhile, two of the three patients with acral melanoma had stable disease and one had progressive disease (RR and DCR were 0% and 66.6%, respectively). Except for the patients treated with palliative RT for bone metastasis in the present study, the RR was 50% (4/8 patients), and the DCR was 75% (6/8 patients). Vitiligo developed after RT in five (50%) patients at a median duration of 2 months after RT. The clinical response and the high occurrence of vitiligo suggest that the combination of RT and anti‐PD‐1 therapy could be effective in some patients with mucosal melanoma.     

Kindler'S syndrome: a case series of three Indian children

Kindler's syndrome is a very rare genodermatosis characterized by acral blistering starting in infancy, photosensitivity, progressive poikiloderma, cutaneous atrophy, and various forms of mucosal involvement. A large number of other cutaneous and extracutaneous features have also been described. We report here three cases of Kindler's syndrome from eastern India for the rarity of the syndrome and to emphasize the importance of considering this condition in the differential diagnosis of disorders that can cause blistering, cutaneous atrophy, and/or poikilodermatous skin changes.     

Amyloidosis cutis dyschromica in two female siblings: cases report

Background

Cutaneous amyloidosis has been classified into primary cutaneous amyloidosis (PCA, OMIM #105250), secondary cutaneous amyloidosis and systemic cutaneous amyloidosis. PCA is the deposition of amyloid in previously apparent normal skin without systemic involvement. Amyloidosis cutis dyschromica (ACD) is a rare distinct type of PCA. Here, the unique clinical and histological findings of two Chinese female siblings with ACD were described.

Cases presentations

Patient 1 was a 34-year-old female, presented with mildly pruritic, diffuse mottled hyperpigmentation and hypopigmentation. The lesions involved all over the body since she was 10 years old. There were a few itchy blisters appearing on her arms, lower legs and truck, especially on the sun-exposed areas in summer. Some hypopigmented macules presented with slight atrophy. Patient 2 was 39-year-old, the elder sister of patient 1. She had similar skin lesions since the same age as the former. The atrophy and blisters on the skin of the patient with amyloidosis cutis dyschromica have not been described in previous literature. Histological examinations of the skin biopsies taken from both patients revealed amyloid deposits in the whole papillary dermis. Depending on the histological assessment, the two cases were diagnosed as amyloidosis cutis dyschromica.

Conclusion

The two cases suggest that the atrophy and blisters may be the uncommon manifestations of amyloidosis cutis dyschromica. It alerts clinicians to consider the possibility of ACD when meeting patients with cutaneous dyschromia. Skin biopsy is essential and family consultation of genetic investigation is very important in such cases.     

Detecting copy number alterations of oncogenes in cell-free DNA to monitor treatment response in acral and mucosal melanoma

BackgroundReliable biomarkers are necessary for assessment of treatment responses. Acral and mucosal melanomas are commonly associated with copy number (CN) alterations rather than specific point mutations, with CN alterations inKIT, CDK4, and CCND1 occurring frequently. Cell-free DNA is released to peripheral blood by both normal and tumor cells, and therefore contains the same genetic alterations present in the source tumor.ObjectiveTo investigate the usefulness of detecting CN alterations in oncogenes in cell-free DNA for monitoring treatment response in acral and mucosal melanomas.MethodsWe isolated cell-free DNA from peripheral blood and assessed the CN alterations in the cell-free DNA. Using droplet digital PCR, we examined CN alterations ofKIT, CDK4, and CCND1 in tumors from 37 melanoma patients (acral, n = 27; mucosal, n = 10) and peripheral blood from 24 melanoma patients (acral, n = 17; mucosal, n = 7).ResultsCN gain was detected in at least one of the genes examined in 62.9 % (17/27) of acral melanomas and 70 % (7/10) of mucosal melanomas. CN gains were also detected in the plasma of some patients. Furthermore, plasma CN ratio was correlated with clinical condition. This correlation was especially clear in patients with high CN ratios in tumors and high tumor burdens.ConclusionPlasma CN ratios may be useful for evaluating treatment responses in patients with acral and mucosal melanoma.     

A review of the solitary cutaneous T‐cell lymphomas

Cutaneous T‐cell lymphomas (CTCL) account for almost 65‐92% of all cutaneous lymphomas, many of which usually present with multiple lesions. However, a number of well‐recognized and rare types of CTCL, including mycosis fungoides, can present in isolated fashion. These solitary lesions often run a relatively indolent clinical course but often pose diagnostic difficulties. We review histopathologically challenging solitary cutaneous T‐cell lymphomas, including criteria for diagnosis, clinical course and prognosis, particularly for primary cutaneous CD4+ small/medium pleomorphic lymphoma and indolent CD8+ lymphoid proliferation of acral sites. In addition, we suggest an algorithm and nomenclature to aid in the diagnosis of such problematic lesions.     

Point mutations in the N-ras oncogene in malignant melanoma and congenital naevi

DNA from formalin-fixed and paraffin-processed samples from 100 melanocytic lesions (39 malignant melanomas, 18 cases of dysplastic naevi, and 43 congenital naevi) was extracted, and the sequences around codons 12/13 and 61 of the N-ras oncogene were amplified using the polymerase chain reaction. The amplified product was then analysed both by dot-blotting and by direct sequencing for point mutations. By the dot-blotting technique, mutations were seen in 18 of 100 lesions. These were in one of five distant metastases (20%), in one of three nodal metastases (33%), in four of 31 (13%) primary melanomas, in none of 18 dysplastic naevi, and in 12 of 43 (28%) congenital naevi, all at codon 61. On direct sequencing, nine of 18 mutations were confirmed, in two of 31 (6%) primary tumours, one distant metastasis, and six of 43 (14%) congenital naevi. Of the 23 superficial spreading melanomas examined, eight were on sun-exposed skin. A superficial spreading melanoma, in which the N-ras mutation at codon 61 was confirmed, was on non-exposed skin, and an unconfirmed mutation was from an exposed site. One of three nodular melanomas with a confirmed mutation was on a light-exposed site, and the other two nodular melanomas were from non-exposed areas. All four lentigo maligna melanomas were from exposed sites, and one of these had an unconfirmed mutation. The only acral lentiginous melanoma, which had no mutation, was from a sun-exposed area. Ten of the 43 congenital or early onset naevi were on sun-exposed sites; six unconfirmed and five confirmed mutations were from lesions on non-sun-exposed sites (5/33; 15%), and one confirmed mutation was from a lesion on a sun-exposed area (1/10; 10%). Our results do not, therefore, support the hypothesis that N-ras mutations are specifically associated with primary melanomas arising on continually sun-exposed skin. The overall pattern suggests that N-ras mutations in isolation in melanocytic lesions are not frequent. This is the first report of N-ras mutations in congenital/early onset melanocytic naevi, and shows a relatively high incidence in comparison with that observed in melanomas in this study.     

Hydroxyurea‐induced dermatomyositis: true amyopathic dermatomyositis or dermatomyositis‐like eruption?

Background Hydroxyurea‐induced dermatomyositis is a rare adverse reaction of long‐term hydroxyurea therapy. It has been reported under different names; however, the exact classification and nomenclature of this eruption have been the subject of much debate, and a more precise term is still awaiting. Herein, we review the different aspects of this reaction and suggest a new term that might help to minimize the confusion about its nomenclature. Materials and methods We describe a 68‐year‐old woman who had been on long‐term hydroxyurea therapy for the treatment of chronic myeloid leukemia for nine years. She presented with typical dermatomyositis‐like lesions and many of the other mucocutaneous adverse effects of hydroxyurea. Results Skin examination revealed typical Gottron’s papules on the dorsa of the hands, atrophy, xerosis, acquired ichthyosis, photosensitivity, cutaneous, oral and nail hyperpigmentation, acral erythema, palmoplantar keratoderma, actinic keratoses, and leg ulcers. There was no clinical or laboratory evidence of proximal muscle weakness. Cessation of hydroxyurea was associated with remarkable improvement of the skin lesions. Conclusion Hydroxyurea‐induced dermatomyositis is a rare drug‐induced dermatomyositis characterized by skin lesions identical to classic dermatomyositis without clinical or laboratory evidence of myositis. We propose that the term hydroxyurea‐induced amyopathic dermatomyositis that adequately describes the findings reported in this subset of patients would be more precise and specific.     

Skin and nail changes in children with sickle cell anemia receiving hydroxyurea therapy

Skin and nail changes from long-term hydroxyurea therapy are reported in adults. Skin and nail changes, including nail hyperpigmentation, longitudinal bands, and hyperpigmentation of the palms and other skin surfaces, developed in 7 children with sickle cell anemia after 6 to 16 weeks of hydroxyurea therapy. Cutaneous and nail changes may occur in children receiving hydroxyurea.     

Evaluation of the atrophogenic potential of topical corticosteroids in pediatric dermatology patients

Abstract: We conducted a cross‐sectional observational study to determine the atrophogenic potential of TCS in children with dermatitis requiring long‐term TCS suppression. Children who were able to achieve good disease control, with a maximum Eczema Area and Severity Index score of 1.0, using TCS were examined for adverse effects of treatment. Cutaneous atrophy was assessed using a validated dermoscopic technique. Cutaneous sites exposed to TCS were compared with nonexposed sites in all patients. There was no significant atrophy in 70 TCS‐exposed and 22 TCS‐naïve children. Mild grade 1 telangiectasia of the cubital fossa was observed in 3.3% of the test group and 3.1% of the control group (p > 0.99). We conclude that routine, appropriate, long‐term use of TCS in children with dermatitis does not cause skin atrophy. These data do not support the widely held belief that routine use of TCS will “thin the skin.” Parents, pharmacists, and health practitioners should be confident about the safety of using this treatment.     

Dermatitis cruris pustulosa et atrophicans revisited: our experience with 37 patients in south India

Background  Dermatitis cruris pustulosa et atrophicans (DCPA) is a distinctive type of chronic superficial folliculitis, with a number of unique features such as its peculiar symmetric localization to legs, extreme chronicity, resistance to therapy, and inevitable alopecia and atrophy.
Methods  All patients with DCPA, attending the Dermatology Outpatient Department at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Hospital, Pondicherry, from December 2006 to June 2008 were included. Parameters recorded were detailed history and examination, hemogram, erythrocyte sedimentation rate, random blood sugar, skin biopsy and cultures from pus and carrier sites (nares, axillae and gluteal fold).
Results  37 patients were studied (35 males and 2 females). Sixteen patients (43.24%) belonged to the 21–30 year-old age group. The disease most commonly began on the legs (81.1%). Majority (78.38%) had a disease duration of less than 5 years. Itching was the most common symptom (89.19%), followed by bleeding and scaling, with no significant systemic symptoms. The lower limbs were involved in all patients. Eleven patients (29.73%) had involvement of other sites – beard, axillae, chest, moustache, abdomen, and eyebrows. Pustules, papules, and scaling were seen in all patients, followed by wiry roughness, atrophy, alopecia, and pigmentation. Aggravating factors included use of full-length synthetic trousers, occupational exposure to potential irritants, and season (summer). Pus culture from the folliculitic lesions grew Staphylococcus aureus in 32 (86.49%) patients. Twenty one patients (56.75%) were carriers of S. aureus in one or more sites.
Conclusion  DCPA is a chronic folliculitis of the legs, with a multifactorial etiopathogenesis, in which staphylococcal carrier status may be a new potential pathogenetic factor.     

拟诊Weary-Kindler综合征一例

患者男,51岁,全身红斑、角化、皮肤异色、肢端水疱7年余,并伴有皮肤萎缩、光敏感、并指、粘膜损害、甲破坏、眼睑内翻、掌趾角化、假阿洪病、龋齿。皮肤病理：表皮角化过度,表皮萎缩,基底细胞液化变性,可见胶样小体。可见一处皮下裂隙,真皮浅层可见大量游离色素和嗜色素细胞。拟诊：Weary-kindler综合征。     

难治性白癜风的治疗进展

近年来白癜风治疗有了长足发展，目前欧洲、英国、日本、中国都制定了相关诊疗共识，大部分患者可以依此制定有效、合理的治疗方案，但白癜风治疗中仍存在难点，如特殊部位白斑（黏膜及薄嫩部位、毛发部位、肢端部位）、大面积白斑和残留不规则白斑的治疗等。针对以上难题本文对近五年来国内外文献进行了综述。     

Perianal and genital basal cell carcinoma: A clinicopathologic review of 51 cases.

BACKGROUND: Basal cell carcinoma (BCC) occurring on non-sun-exposed sites, especially the perianal and genital regions, is very rare. OBJECTIVE: We analyzed the incidence, clinical and pathologic features, and etiologic and prognostic factors of all non-nevoid perianal and genital BCCs diagnosed at our institution within a defined period (January 1985-September 1996). METHODS: A retrospective review was performed with the use of patient clinical records and dermatopathologic slides. Cutaneous biopsy samples were tested for the presence of human papillomavirus (HPV) by in situ hybridization using biotinylated pan-HPV and serotype-specific (6, 11, 16, 18, 31, 33, 51) probes. RESULTS: Of all non-nevoid BCC syndrome cases, 51 BCCs (0.27%) were located within the perianal and genital regions. The average age of the patients was 73 years. Nine perianal BCCs occurred in men, 6 in women. Ten BCCs occurred in the pubic area, 18 on the vulva, 6 on the scrotum, and 2 on the penis. Three patients had 2 tumor sites. The average size of BCC was 1.95 cm; 29.4% were ulcerated. Seventeen patients (36%) had a history of skin cancer on sun-exposed sites and 10 (21%) had a possibly relevant associated condition. HPV was not detected in the specimens tested. Treatments included wide excision (n = 32), electrodesiccation and curettage (n = 10), Mohs micrographic surgery (n = 8), and carbon dioxide laser (n = 1). Of 30 patients with 5 years' follow-up or longer, 1 recurrence was noted 7 years after wide excision. There were no metastases. CONCLUSION: BCC of the perianal and genital skin is rare and exhibits clinical and histologic heterogeneity. Advancing age and local trauma may contribute to the pathogenesis of BCC at these sites.     

Epidermal innervation correlates with severity of photodamage

Abstract Intraepidermal nerve fibers were studied by electron microscopy in chronically photodamaged preauricular skin and in paired sun-protected postauricular sites of 20 Caucasian women aged 56–70 years. As previously reported, basal keratinocytes in the sun-exposed skin showed various degrees of degenerative changes including intracellular vacuolar structures and widened intercellular spaces. Neurites were frequently closely apposed to basal keratinocytes in preauricular sun-exposed skin, but were observed less than 10% as often in sun-protected postauricular skin. When degree of epidermal photodamage was quantified by means of the number of degenerated keratinocytes per 100 keratinocytes in the basal layer, the number of intraepidermal nerve libers was significantly correlated by linear regression analysis to the severity of epidermal photodamage (r=0.913) independent of anatomical sites. These results demonstrate for the first time a correlation between degree of epidermal innervation and chronic photodamage and suggest the possibility of neural involvement in the pathophysiology and/or repair of photodamaged skin.     

Comparison of protoporphyrin IX accumulation and destruction during methylaminolevulinate photodynamic therapy of skin tumours located at acral and nonacral sites

Background Topical photodynamic therapy (PDT) is successful in the treatment of nonmelanoma skin cancers and associated precancers, but efficacy is significantly reduced in actinic keratosis lesions not located on the face or scalp. Objectives To compare the changes in protoporphyrin IX (PpIX) fluorescence in lesions undergoing routine methylaminolevulinate (MAL) PDT and the clinical outcome observed 3 months after treatment in lesions located at acral and nonacral sites. Methods This study was a noninterventional, nonrandomized, observational study, which monitored changes in PpIX fluorescence in 200 lesions during standard dermatological MAL‐PDT. These data were subsequently analysed in terms of lesions located at acral and nonacral sites. Results Clinical clearance was significantly reduced (P < 0·01) in acral skin lesions when compared with lesions located at nonacral sites. The accumulation and destruction of PpIX fluorescence was significantly reduced in these acral lesions (P < 0·05 and P < 0·001, respectively). Specifically, lesion location at acral sites significantly reduced changes in PpIX fluorescence in actinic keratosis lesions during MAL‐PDT (P < 0·01 and P < 0·05). Conclusions These data suggest that reduced PpIX accumulation and the subsequent reduction in PpIX photobleaching within acral lesions result in the reduced responsiveness of these lesions to MAL‐PDT. Future work should therefore aim to improve photosensitizer accumulation/photobleaching within lesions located at acral sites.     

Skin as an indicator for sexually transmitted infections

Cutaneous signs and skin conditions associated with sexually transmitted infections (STIs) are discussed. Syphilis, condyloma acuminata, and scabies are well-known STIs with cutaneous manifestations. Chlamydia and gonorrhea can also cause specific muco-cutaneous signs and symptoms. HIV often manifests itself through skin conditions. Dermatologists are pivotal in the timely diagnosis of HIV infection and play an important role in the disease prognosis and ongoing transmission. Anal intra-epithelial neoplasia (AIN), an HPV related precursor of anal carcinoma affecting HIV positive men, is a relatively new condition that many dermatologists will face in the future. STIs should be involved in the differential diagnosis when dermatologists are confronted with anogenital dermatoses, especially in patients with an increased risk for STIs.