Compound heterozygous CORO1A mutations in siblings with a mucocutaneous-immunodeficiency syndrome of epidermodysplasia verruciformis-HPV, molluscum contagiosum and granulomatous tuberculoid leprosy.

PURPOSE: Coronin-1A deficiency is a recently recognized autosomal recessive primary immunodeficiency caused by mutations in CORO1A (OMIM 605000) that results in T-cell lymphopenia and is classified as T(-)B(+)NK(+)severe combined immunodeficiency (SCID). Only two other CORO1A-kindred are known to date, thus the defining characteristics are not well delineated. We identified a unique CORO1A-kindred. METHODS: We captured a 10-year analysis of the immune-clinical phenotypes in two affected siblings from disease debut of age 7 years. Target-specific genetic studies were pursued but unrevealing. Telomere lengths were also assessed. Whole exome sequencing (WES) uncovered the molecular diagnosis and Western blot validated findings. RESULTS: We found the compound heterozygous CORO1A variants: c.248_249delCT (p.P83RfsX10) and a novel mutation c.1077delC (p.Q360RfsX44) (NM_007074.3) in two affected non-consanguineous siblings that manifested as absent CD4CD45RA(+) (naïve) T and memory B cells, low NK cells and abnormally increased double-negative (DN) ϒδ T-cells. Distinguishing characteristics were late clinical debut with an unusual mucocutaneous syndrome of epidermodysplasia verruciformis-human papilloma virus (EV-HPV), molluscum contagiosum and oral-cutaneous herpetic ulcers; the older female sibling also had a disfiguring granulomatous tuberculoid leprosy. Both had bilateral bronchiectasis and the female died of EBV+ lymphomas at age 16 years. The younger surviving male, without malignancy, had reproducibly very short telomere lengths, not before appreciated in CORO1A mutations. CONCLUSION: We reveal the third CORO1A-mutated kindred, with the immune phenotype of abnormal naïve CD4 and DN T-cells and newfound characteristics of a late/hypomorphic-like SCID of an EV-HPV mucocutaneous syndrome with also B and NK defects and shortened telomeres. Our findings contribute to the elucidation of the CORO1A-SCID-CID spectrum.

Histopathological study of cutaneous manifestations in HIV and AIDS patients.

OBJECTIVES: Most human immunodeficiency virus (HIV)-infected patients develop various skin diseases. These skin manifestations not only act as markers but also reflect the patient's underlying immune status. Investigating CD4 counts is costly and not always possible. Thus, the potential value to be gained by using skin manifestations as predictors of low CD4 counts and disease progression should be explored. The present study attempted to correlate the association of various cutaneous disorders found in HIV patients with CD4 and CD8 counts, the CD4 : CD8 ratio and stage of HIV infection. METHODS: This was a prospective study involving 61 patients who were HIV-positive and demonstrated skin lesions. Punch biopsies of skin were taken for histopathological diagnosis. CD4 and CD8 T cell counts were performed. RESULTS: The study sample included a majority of male patients, most of whom were aged 21-40 years. Pruritic papular dermatitis was the most common skin manifestation, followed by molluscum contagiosum, eosinophilic folliculitis, and Hansen's disease. Most of the lesions were associated with CD4 counts of <220/µl (n = 38). All skin lesions associated with HIV or acquired immune deficiency syndrome (AIDS) showed a CD4 : CD8 ratio of <0.50. CONCLUSIONS: The study findings demonstrate an inverse relationship between CD4 counts and the occurrence of skin lesions. The majority of lesions were associated with stage 3 or stage 4 infection. Thus, specific cutaneous manifestations can be considered as good clinical indicators for predicting underlying immune status in resource-poor countries.

Molluscum contagiosum-like lesions in histoid leprosy in a 10-year-old Indian boy.

Histoid leprosy is extremely rare in children. Molluscum contagiosum-like lesions in the setting of histoid leprosy is a highly atypical presentation and may signify the process of "transepidermal elimination" in lesions with high bacillary load. A case of histoid leprosy with umbilicated papules and nodules mimicking molluscum contagiosum is reported in a 10-year-old Indian boy.

An open, nonrandomized, comparative study of imiquimod 5% cream versus 10% potassium hydroxide solution in the treatment of molluscum contagiosum.

BACKGROUND: There are numerous therapeutic modalities available for treatment of molluscum contagiosum. However, the ablative modalities are painful and not suitable for children. AIM: We aimed to evaluate and compare the safety and efficacy of 2 of the painless modalities, viz., 5% imiquimod cream and 10% potassium hydroxide (KOH) solution, in the treatment of molluscum contagiosum. METHODS: Out of a total of 40 patients of molluscum contagiosum in the study, 18 patients in the imiquimod group and 19 patients in the KOH group completed the study. The given medication was applied by the patient or a parent to mollusca at night, 3 days per week. Imiquimod was continued till clinical cure; and 10% KOH, till lesions showed signs of inflammation. Assessments of response and side effects were performed at the end of week 4, week 8, and week 12. Significance was tested by Student's t test and Mann-Whitney test. RESULTS: The mean lesion count decreased from 22.39 to 10.75 with imiquimod and from 20.79 to 4.31 with KOH at the end of 12 weeks. We found complete clearance of lesions in 8 (44%) patients with imiquimod and in 8 (42.1%) patients with 10% KOH. Minor side effects were seen in 15 (78.9%) patients on KOH and 10 (55.5%) patients on imiquimod. CONCLUSIONS: The results of this study suggest that both 5% imiquimod cream and 10% KOH solution are equally effective in molluscum contagiosum though KOH has a faster onset of action. However, KOH solution is associated with a higher incidence of side effects.

AIDS and HIV infections: uncommon presentations.

Infection with HIV or AIDS has a great impact on skin diseases, not only by affecting the immune system and thereby host defense against bacterial, viral, or mycotic infection, but also by changing tumor immune response and autoimmune reactivity. In the present review, emphasis will be made on infectious diseases, including sexually transmitted disease, inflammatory skin disease, and neoplasias. Knowledge of changing disease pattern with HIV/AIDS may help the clinical dermatologist and venerologist to identify dermatoses and act in the most appropriate manner to support the patient.

Molluscum contagiosum-like lesions in lepromatous leprosy.

A 32-year-old male patient presented with multiple, asymptomatic, papulonodular lesions some of which were umbilicated simulating the clinical features of molluscum contagiosum. On examination the patient was found to be suffering from lepromatous leprosy. Slit-skin smear showed a BI of 6+ and histopathological examination of the nodular lesion showed features of lepromatous leprosy. The patient was treated with MDT-MB and improved remarkably in a few months.

Molluscum contagiosum-like lesions in lepromatous leprosy.

A 23-year old male presented with multiple, asymptomatic, raised lesions of 4 months' duration. The lesions were well demarcated. Dome-shaped papules and nodules were seen on normal looking skin; some were shiny, pearly white and umbilicated. Bilateral greater auricular, ulnar, radial cutaneous and lateral popliteal nerves were thickened. Slit skin smear from an umbilicated nodule had a BI of 6+. Biopsy showed features of lepromatous leprosy.