Özay Gököz

Additional Diverse Findings Expand the Clinical Presentation of DOCK8 Deficiency

We describe seven Turkish children with DOCK8 deficiency who have not been previously reported. Three patients presented with typical features of recurrent or severe cutaneous viral infections, atopic dermatitis, and recurrent respiratory or gastrointestinal tract infections. However, four patients presented with other features. Patient 1–1 featured sclerosing cholangitis and colitis; patient 2–1, granulomatous soft tissue lesion and central nervous system involvement, with primary central nervous system lymphoma found on follow-up; patient 3–1, a fatal metastatic leiomyosarcoma; and patient 4–2 showed no other symptoms initially besides atopic dermatitis. Similar to other previously reported Turkish patients, but in contrast to patients of non-Turkish ethnicity, the patients’ lymphopenia was primarily restricted to CD4+ T cells. Patients had homozygous mutations in DOCK8 that altered splicing, introduced premature terminations, destabilized protein, or involved large deletions within the gene. Genotyping of remaining family members showed that DOCK8 deficiency is a fully penetrant, autosomal recessive disease. In our patients, bone marrow transplantation resulted in rapid improvement followed by disappearance of viral skin lesions, including lesions resembling epidermodysplasia verruciformis, atopic dermatitis, and recurrent infections. Particularly for patients who feature unusual clinical manifestations, immunological testing, in conjunction with genetic testing, can prove invaluable in diagnosing DOCK8 deficiency and providing potentially curative treatment.

Transfusion-associated graft-versus-host disease in immunocompetent patients: case series and review of the literature

BACKGROUND: Transfusion‐associated graft‐versus‐host disease (TA‐GVHD) is a fatal complication of transfusion of blood products that usually affects immunocompromised patients. Articles reporting this condition in immunocompetent recipients are usually from countries that still have problems in irradiation of blood products.

Sweet's syndrome and erythema nodosum: a companionship or a spectrum?--a case report with review of the literature.

A 47-year-old woman presented to the emergency department with an eruption of 4 days’ duration. The eruption started on the face, neck, and hands. Later, lesions appeared on the arms and legs, accompanied by arthralgia. She had a 9-day history of an upper respiratory tract infection for which she was prescribed levofloxacin and acetaminophen. She recalled that she had also used dipyrone during the prodromal phase of the infection. In addition, she had suffered from vitiligo for 20 years, together with hypertension, hyperlipidemia, and fibromyalgia. Dermatologic examination revealed the following: on the face, ears, and ‘V’ region and back of the neck, erythematous and highly edematous papules and plaques, some of which were pseudovesicular (Fig. 1); at the extensor surfaces of the arms, erythematous, pustular papules and plaques with some dusky red centers, resembling target lesions; at the dorsal and palmar surfaces of the hands, painful, highly edematous plaques, some of which were also targetoid, and multiple separate tiny pustules; at the anterior aspects of the legs, 10–20 pale, erythematous, painful, indurated nodules (Fig. 2), accompanied by similar lesions on the sides of the thighs and on the dorsum of the left foot. All other aspects of the dermatologic examination, including the oral mucosa, scalp, and nails, were normal, except for the depigmented macules and patches on the dorsal surfaces of the hands and volar surfaces of the wrists, which were consistent with vitiligo. The rest of the physical examination was normal. There was no lymphadenopathy. The liver function tests were normal. She had leukocytosis [20.6 · 10/L; normal, (4–10) · 10/L], with a neutrophilic predominance of 78% in the peripheral smear, and an elevated C-reactive protein level (5.35 mg/ dL; normal, 0–0.8 mg/dL) and sedimentation rate (96 mm/h; normal, 0–20 mm/h). She had anemia with a hemoglobin level of 10 g/dL (normal, > 12 g/dL for females). She was hospitalized and systemic corticosteroid therapy was initiated with the clinical diagnosis of Sweet’s syndrome. All samples, including an excisional skin biopsy obtained from one of the lesions on the leg and punch biopsies taken from the neck and from one of the

Clinical and histopathological response to acitretin therapy in lipoid proteinosis.

Abstract Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis associated with deposition of periodic acid-Shiff (PAS)-positive hyaline material in skin, mucosa, and other tissues. LP is caused by loss-of-function mutations in the extracellular matrix protein 1 gene (ECM1). No curative therapy is available. In this report, we describe the clinicopathological and genetic features of a Turkish LP family with four cases, and evaluate the response of acitretin therapy. Patients were presented with hoarseness and beaded eyelid papules, thickened frenulum, hyperkeratotic plaques and infiltrated warty papules and nodules. Skin biopsies revealed deposition of PAS-positive hyaline material in dermis. A homozygous nonsense mutation in exon 3 of the ECM1 gene, R53X, was detected in the family. Acitretin therapy was administered in two patients, in whom some regression and softening of skin lesions were achieved. However, no histopathological change in PAS-positive deposition could be detected. Although there is no current effective treatment for LP, acitretin may be helpful for patients, especially those who complain about hyperkeratosis.

A case of bullous pemphigoid ınduced by vildagliptin

Abstract Bullous pemfigoid (BP), an autoimmune disorder, can also be induced by some medications. Vildagliptin is a new drug used to treat diabetes mellitus (DM). Recently, a few cases of vildagliptin-induced BP have been described in the literature. We report a patient with BP in which vildagliptin was thought to be as a possible causative agent. The awareness of BP development risk during gliptin therapy can prevent unnecessary usage of systemic drugs with serious side effects.

A resistant case of pemphigus gestationis successfully treated with intravenous immunoglobulin plus cyclosporine

erythematosus Editor, A 44-year-old woman was admitted to our hospital with a 3-year history of generalized progressive erythematosquamous skin lesions. This condition had been diagnosed elsewhere as pemphigus erythematosus. Treatment with oral methylprednisolone at 80 mg per day was administered and achieved a good response. However, when the corticosteroids were slowly withdrawn, the condition relapsed, and the patient became very nervous and distressed about her facial lesions. Subsequently, she developed phobic anxiety and avoided facial cleaning and any outdoor activity. The lesions had begun as dark yellow papules on the forehead and had gradually increased to involve the whole face and scalp. Physical examination revealed thick, dark brown crusts covering most of the subjects face and red macules with purulent fluid on the cheeks (Fig. 1). A skin biopsy and direct immunofluorescence confirmed the diagnosis of pemphigus erythematosus. Anti-Dsg1 immunoglobulin G (IgG) antibodies were detected by enzyme-linked immunosorbent assay (ELISA) (120 U/ml). The patient was treated with prednisone 60 mg per day for seven days. However, when the adherent crust was removed using 0.9% normal saline, the underlying skin was found to be almost normal (Fig. 2). We tapered the dose of prednisone to 40 mg per day. There was no relapse of the skin lesions. Cutaneous dirt-adherent disease (CDAD) is a rare psychogenic dermatosis that occurs mainly in young Japanese and Chinese women. Its psychological pathogenesis remains largely unclear. To our knowledge, this is the first case of CDAD on a base of pemphigus to be reported. The skin lesions of CDAD can be confused with the oozing and crusts of pemphigus, which may lead to an erroneous diagnosis of severe pemphigus and an inappropriate increase in the dose of corticosteroid.

Clinical and histopathological characteristics of a family with R1141X mutation of pseudoxanthoma elasticum – presymptomatic testing and lack of carrier phenotypes

Pseudoxanthoma elasticum (PXE) is a heritable ectopic mineralization disorder affecting cutaneous, ocular, and cardiovascular systems, caused by mutations in the ABCC6 gene. PXE presents with a marked clinical and genetic heterogeneity. Furthermore, heterozygous carriers may present with limited histopathological features. This study was conducted to investigate a patient with PXE and her family members clinically, histopathologically, and genetically.

Nevus-Associated versus de novo Melanoma: Do They Have Different Characteristics and Prognoses?

Aim: The aim of this study was to determine if nevus-associated melanoma differs in characteristics and prognosis from de novo melanoma. Patients and Methods: The study included 118 melanoma patients. Clinical findings were retrospectively evaluated. For histopathological parameters, HE sections were reexamined. The differentiation between de novo and nevus-associated melanoma was based on the histopathological evidence of a precursor nevus. In addition, all analyses were repeated in all cases in which nevus-associated melanoma was defined based on patient anamnesis. Results: Among all patients, 28 (23.7%) had nevus-associated melanoma. Nevus-associated melanoma was most commonly located on the extremities (50%), followed by the trunk (25%), whereas de novo melanoma was most commonly located in the head and neck region (32.2%), followed by the acral region (31.1%). Other clinical findings and histopathological parameters did not differ significantly between the two groups (p > 0.05). The findings remained consistent following the repeated analysis of all cases in which nevus-associated melanoma was defined based on patient anamnesis. Conclusions: Nevus-associated melanoma was most commonly located on the extremities and the trunk, whereas de novo melanoma was most commonly located in the head and neck and the acral region. Furthermore, nevus-associated melanoma was similar to de novo melanoma in terms of prognosis and other disease characteristics.

Syringocystadenoma papilliferum arising on naevus sebaceus: A 6-year-old child case described with dermoscopic features

Naevus sebaceus (NS) has a well-documented potential to develop a wide variety of benign or malignant neoplasms of both epidermal and adnexal origins, especially at puberty or adulthood. Syringocystadenoma papilliferum (SCAP) is a rare cutaneous adnexal neoplasm with variable clinical appearance but characteristic histology. It is one of the most common benign tumours developing on NS. Childhood cases of SCAP arising on NS are rare. Furthermore, there is only one report describing the dermoscopic features of SCAP arising on NS. A 6-year-old boy presented with a pruritic papule over a hairless area on his scalp that had been present since birth. A dermatological examination revealed a 2 × 1 cm yelloworange hairless plaque over the occipital scalp consistent with NS, with a flesh-colored papule on its left side (Fig. 1). A non-polarised dermoscopic examination of the papule revealed central yellowish-white discolouration with polymorphic vessels including irregular dotted, hairpin-like, glomerular and linear vessels and a surrounding pinkishwhite rim with peripheral hairpin-like vessels (Fig. 2). A histopathological examination of the papule revealed cystic invaginations extending into the dermis, with numerous papillary projections and stroma rich in plasma cells, consistent with SCAP (Fig. 3). The parents were informed about the risk of an although rare, malignant transformation and new tumours that would probably arise on NS, and elective total excision before puberty was suggested. The actual value of dermoscopy in the diagnosis of adnexal tumours is not yet known. As far as we know, there is only one case report describing the dermoscopic features of SCAP. In this case, Bruno and colleagues reported a polymorphous vascular pattern including irregular linear and glomerular vessels, some of which were surrounded by a whitish halo and others grouped in a horseshoe arrangement on a pinkish-white background. In our patient we observed polymorphic vessels including irregular, dotted, hairpin-like, glomerular and linear vessels on a central yellowish-white discoloration and a surrounding pinkishwhite rim with peripheral hairpin-like vessels. However, we do not know if those dermoscopic features are specific for SCAP, whether or not it arises on NS. Additionally, the lesion in our patient was pruritic, therefore we do not know if some of the vascular features are secondary to scratching and the healing of scratches or trauma due to brushing and so on, rather than reflecting the SCAP per se. Various types of vessels were reported in a dermoscopic evaluation of adnexal tumours. Crown vessels were described in sebaceous hyperplasia, arborising vessels were shown in cylindroma, hidradenoma and intraepidermal poroma. In a recent study with 13 cases of nonpigmented ecrine poroma, a polymorphous vascular pattern was found in most cases. Four lesions presented with irregular linear and branched vessels with semi-elliptical or semicircular endings, which the authors named as chalice-form and cherry-blossoms vessels. In conclusion, our case provides evidence that tumours such as SCAP can develop on NS in patients as young as

Investigation of BRAF mutation analysis with different technical platforms in metastatic melanoma

In metastatic melanoma, the detection of somatic mutations in the BRAF gene is crucial regarding patient selection for targeted therapy. Several screening methods have been developed to identify BRAF gene mutations. In this study, our objective was to evaluate the detection of the BRAF V600 mutations using two molecular methods, real-time polymerase chain (real-time PCR) assay and pyrosequencing, and immunohistochemistry (IHC), and to compare the results of these different technical platforms. This study included 98 patients diagnosed with metastatic melanoma at the Hacettepe University, Department of Pathology between 2002 and 2014. BRAF mutation analysis was tested with real-time PCR, pyrosequencing and IHC methods. The results of all three tests were compared with a reference test, and the sensitivity, specificity rates and kappa coefficient values were analysed for each test. We successfully analysed BRAF mutations using all three methods in 92 patients. According to our findings, the pyrosequencing method had the highest kappa value regarding the determination of BRAF V600 mutations. The kappa values were at almost perfect agreement levels in pyrosequencing and real-time PCR assay (kappa coefficient for pyrosequencing=0.895 (95% CI: 0.795-0.995); kappa coefficient for real-time PCR=0.871 (95% CI: 0.761-0.981). The kappa value was at a substantial agreement level in the IHC analysis (kappa coefficient=0.776 (95% CI: 0.629-0.923). According to our results, we found that real-time PCR and pyrosequencing methods were equally excellent in determination of BRAF V600 mutations. The IHC method, which is commonly used in routine pathology practice, can also be safely used as a screening test for determination of BRAF V600 mutations.