Diffuse dermal melanocytosis in two patients with Sandhoff disease and mucopolysaccharidosis VI.

Dermal melanocytosis (DM) is described as the presence of ectopic melanocytes in the dermis and could be a normal cutaneous finding. However, diffuse DM or extensive Mongolian spots must be considered as an early sign of neurometabolic diseases, in particular lysosomal storage disorders. The presence of extensive DM should alert the physician to the presence of such disorders, making early diagnosis possible. We describe for the first time the presence of DM in two patients with Sandhoff disease and mucopolysaccharidosis VI.

Cutaneous granulomas in common variable immunodeficiency: case report and review of literature.

Common variable immunodeficiency (CVID) is a heterogeneous disease characterized by recurrent infections, autoimmunity, malignancies, and granulomatous inflammation. Granulomatous lesion is one of the important manifestations of CVID, which continues to be unknown to many clinicians. While noncaseating granulomatous lesions can be detected in lungs, liver, spleen or conjunctiva of CVID patients, there are only few reported cases with skin granuloma. This report presents a 27-year-old female with multiple persistent cutaneous granulomatous lesions on both hands. The patient had been well until age of 20 years, when she developed these skin lesions and frequent upper respiratory infections and bacterial pneumonia. Also, she experienced recurrent diarrhea (more than 10 episodes). Laboratory evaluation showed decreased serum levels of all immunoglobulin isotypes and low specific antibody responses. The diagnosis of CVID was based on clinical and laboratory findings. Intravenous immunoglobulin therapy at a dosage of 400-500 mg/kg monthly was introduced and improved skin lesions. In conclusion, taking history of recurrent infections and measuring immunoglobulin levels can be suggested in patients with granulomatous lesions instead of other expensive tests.

Characterization of 11 new cases of leukocyte adhesion deficiency type 1 with seven novel mutations in the ITGB2 gene.

BACKGROUND: Leukocyte adhesion deficiency type 1 (LAD I) is an autosomal recessive disorder caused by mutations in the ITGB2 gene, encoding the beta2 integrin family. Severe recurrent infections, impaired wound healing, and periodontal diseases are the main features of disease. METHODS: In order to investigate clinical and molecular manifestations of new LAD I cases, 11 patients diagnosed in one center during 7 years were studied. Patients were screened for the ITGB2 gene mutations, using polymerase chain reaction, followed by single-strand conformation polymorphism and sequencing. RESULTS: The most common first presenting feature of the patients was omphalitis. The mean age of cord separation was 19.9 +/- 1 days. The most common clinical manifestations of the patients during the follow-up period included omphalitis, skin ulcers with poor healing, sepsis, and otitis media. During the follow-up, eight patients died. Eight homozygous changes, including seven novel mutations, were detected: two splicing (IVS4-6C>A, IVS7+1G>A), three missense (Asp128Tyr, Ala239Thr, and Gly716Ala), and three frameshift deletions (Asn282fsX41, Tyr382fsX9, and Lys636fsX22). CONCLUSION: Our results indicate that different mutations underlie the development of LAD I. Definitive molecular diagnosis is valuable for genetic counseling and prenatal diagnosis. Regarding clinical presentations, it seems that omphalitis is the most consistent finding seen in LAD I infants.

Functional characterization of two RAB27A missense mutations found in Griscelli syndrome type 2.

Human Griscelli syndrome type 2 (GS-2) is characterized by partial albinism and a severe immunologic disorder as a result of RAB27A mutations. In melanocytes, Rab27A forms a tripartite complex with a specific effector Slac2-a/melanophilin and myosin Va, and the complex regulates melanosome transport. Here, we report a novel homozygous missense mutation of Rab27A, i.e. K22R, in a Persian GS-2 patient and the results of analysis of the impact of the K22R mutation and the previously reported I44T mutation on protein function. Both mutations completely abolish Slac2-a/melanophilin binding activity but they affect the biochemical properties of Rab27A differently. The Rab27A(K22R) mutant lacks the GTP binding ability and exhibits cytosolic localization in melanocytes. By contrast, neither intrinsic GTPase activity nor melanosomal localization of Rab27A is affected by the I44T mutation, but the Rab27A(I44T) mutant is unable to recruit Slac2-a/melanophilin. Interestingly, the two mutations differently affect binding to other Rab27A effectors, Slp2-a, Slp4-a/granuphilin-a, and Munc13-4. The Rab27A(K22R) mutant normally binds Munc13-4, but not Slp2-a or Slp4-a, whereas the Rab27A(I44T) mutant shows reduced binding activity to Slp2-a and Munc13-4 but normally binds Slp4-a.

Treatment of pemphigus vulgaris with mycophenolate mofetil as a steroid-sparing agent.

Pemphigus vulgaris is a rare autoimmune blistering disease. Estimation of the incidence in Iran is one patient per 100,000 of the population per year. Mycophenolate mofetil is an immunosuppressive drug and successful treatment of pemphigus vulgaris and bullous pemphigoid has been reported with it, in combination with high dose prednisone, or as monotherapy. The present study describes our experience of the adjuvant use of mycophenolate mofetil in the management of 31 patients with pemphigus vulgaris as an initial treatment. We evaluated the efficacy and safety of mycophenolate mofetil combined with prednisolone in this cohort. We also assessed the relationship between the demographic indices/disease severity factors, and the failure of this treatment. In this study, mycophenolate mofetil was of definite benefit in 21 cases (67.7%). Generalized forms; patients with higher sum of the clinical scores at presentation; severe involvement of the groin; chest; face and limbs and those who had nail dystrophy also appeared to have poorer responses. When we excluded patients with generalized forms, only four patients were included in the failure group and the response rate reached 83.3%. It can be concluded that, except for generalized diseases, mycophenolate mofetil can be used safely and effectively in patients with pemphigus vulgaris as a first line, steroid sparing agent.

Analysis of RAB27A gene in griscelli syndrome type 2: novel mutations including a deletion hotspot.

INTRODUCTION: Griscelli syndrome type 2 is an autosomal recessive disorder characterized by pigmentary dilution and occurrence of acute phases of hemophagocytosis. The disease is caused by mutations in RAB27A gene, coding a small GTPase involved in terminal phases of cytotoxic granule/melanosome exocytosis. MATERIALS AND METHODS: We describe the result of mutation analysis among nine patients from seven non-related Persian families. We present four novel mutations including a deletion hot spot (514del 5). CONCLUSION: This hot spot is flanked by "direct repeats" of nucleotides, which are previously shown to be associated with areas of recurrent small deletions.

Aggressive and neglected basal cell carcinoma.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cutaneous malignancy and usually has a benign coarse. Rarely, examples of aggressive and neglected types of this tumor are seen. OBJECTIVE: To present an interesting and dramatic example of how some people neglect their tumors and how devastating the sequelae can be. METHODS: We report a 58-year-old man with an extensive BCC and signs of cranial nerve involvement. RESULTS: The patient had a large, infected ulcer on his scalp. He also had skull bone destruction, osteomyelitis, mastoiditis, cranial nerve paralysis, and radiographic features of the skull base and upper cervical soft tissue involvement. Pathologic studies revealed an infiltrating form of BCC. CONCLUSIONS: If left untreated and neglected, as in this case, BCC can become inoperable and complicated.