Obiltoxaximab: A Monoclonal Antibody for Cutaneous Anthrax

You should certainly hope that you will never have to use it, but it is still important to know about obiltoxaximab (Anthim), a monoclonal antibody administered by injection, that has been approved for treating inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs in adult and pediatric patients.

It is also approved for prophylaxis of inhalational anthrax when alternatives are not available or appropriate (Kaufman, 2016).

Why should dermatologists care? Because the most common type of human anthrax is the cutaneous form. Other forms of human anthrax (gastrointestinal, inhalational, or injectional) are rare (Kajfasz, 2014).

It is expected that the main use of obiltoxaximab is likely to be in the setting of bioterrorism, but it might also be effective for the rare patient in your practice with cutaneous anthrax.


References

Kaufman MB. Pharmaceutical Approval Update. P T. 2016;41:355-6.

Kajfasz P, Bartoszcze M, Borkowski PK, Basiak W. Retrospective review of the case of cutaneous anthrax-malignant pustule from 1995 in 15-year old girl. Przegl Epidemiol. 2014;68:657-9.

Infectious Disease 2016: Chikungunya

Dr. Sheila Fallon-Friedlander

Dr. Sheila Fallon-Friedlander

Dr. Sheila Fallon-Friedlander

Chikungunya: Dengue-lite?

Chikungunya is an arthropod-borne virus (arbovirus) endemic to West Africa that causes acute febrile polyarthralgia and arthritis. The name chikungunya is derived from a local language of Tanzania meaning “that which bends up” or “stooped walk” because of the incapacitating arthralgia caused by the disease. Chikungunya in neonates is a very rare entity and a diagnostic challenge. Newborns with this infection generally require admission to pediatric intensive care, and related support, due to severe clinical manifestations, which include respiratory distress, sepsis, necrotizing enterocolitis, meningoencephalitis, myocarditis, edema, bullous dermatitis and pericarditis. The case fatality rate for congenital Chikungunya virus infection has been reported to be >30%.

In the acute stage, diagnosis is possible with reverse transcription polymerase chain reaction or serology. Anti-Chikungunya virus IgM antibodies are detectable after an average of 2 days (range = 1-12 days) by enzyme-linked immunosorbent assay and remains positive for several weeks to 3 months.

Infectious Disease 2016: MRSA

Dr. Theodore Rosen

Dr. Theodore Rosen

Dr. Theodore Rosen

Smoking and treatment of methicillin-resistant Staphylococcus aureus (MRSA): apparently cigarette smoke isn’t deadly for all living creatures

Results from a recent study have shown that cigarette smoke may make MRSA more virualent. Researchers at the University of California in San Diego infected macrophages with MRSA that were grown normally or with exposure to cigarette smoke extract. While macrophages were equally able to take up the two bacterial populations, smoke-exposed MRSA were more resistant to killing by reactive oxygen species (i.e., the macrophage oxygen burst). In addition, the smoke-exposed MRSA were more resistant to killing by naturally produced antimicrobial peptides and more adherent to keratonocytes. Additional in vivo experiments in mice showed pneumonia resulting from that smoke-exposed MRSA pneumonia was associated with higher mortality (40% vs 10%) and increased bacterial burden compared to control MRSA-infected mice

Dr. Aditya K Gupta

Infectious Disease 2016: Onychomycosis

Dr. Aditya K Gupta

Dr. Aditya K Gupta

Dr. Aditya K Gupta

Onychomycosis is an infection of the nail plate that is prevalent among the ageing population. Onychomycosis is difficult to treat with low initial cure rates, high rates of relapse, and reinfection. Changing demographic characteristics, such as the relative aging of the population, the increasing prevalence of diabetes and peripheral vascular disease, widespread iatrogenic immunosuppression, and changes in lifestyle (e.g., earlier and greater participation in sports), are likely to lead to an increased prevalence of onychomycosis in both adults and children. Mixed infections of dermatophytes and nondermatophyte molds are increasing in patients with onychomycosis. One recent case series indicated the presence of mixed infections in 41% of patients.

There have been a number of important advances in the treatment of onychomycosis.

New topical agents approved in the US for the treatment of onychomycosis are solutions with lower viscosity and increased nail penetration characteristics. These agents penetrate through the transungual route and via the space between the nail plate and the nail bed. The subungual route partially circumvents the thickness of the nail plate. Laser therapy has been promoted as one of the most promising device-based therapies for onychomycosis. Clinical trial and anecdotal results to date have varied greatly and the specific mechanism of action for this intervention has not been well-elucidated. Overall, this therapy provides cosmetic improvement, but is does not appear to treat the underlying disease. Combining nail drilling with antimycotic treatment has recently been shown to be effective for the treatment of onychomycosis. Treatment with holes plus topical terbinafine produces significantly greater improvement in toenails’ appearance and higher mycological cure rates compared to treating the dorsal aspect of the nail plate with topical terbinafine alone. Overall, early treatment is the path to cure in patients with onychomycosis. The chance of success is better when you treat early.

Recurrence (relapse or re-infection) occurs in 10% to 53% of patients of patients with onychomycosis. However, data on recurrence is limited by the fact that clinical studies have followed patients beyond 12 months. Although a number of factors have been suggested to play a role in recurrence, only the co-existence of diabetes has been shown to have a significant impact. A small study showed that amorolfine prophylaxis may delay recurrence, but prophylaxis may need to be continued for up to 3 years for optimal effect. Treating tinea pedis and any immediate family members may also decrease risk for recurrence; and other preventative strategies include avoiding communal areas where infection can spread and decontaminating footwear.

Dr. Aditya K Gupta

Infectious Disease 2016: HIV/AIDS

Dr. Aditya K Gupta

Dr. Mark Jacobson

Dr. Mark Jacobson

Antiretroviral therapy (ART) for the treatment of HIV infection has improved steadily since the advent of potent combination therapy in 1996 and it has transformed HIV infection into a manageable chronic condition. However, fewer than one-third of HIV-infected individuals in the United States have suppressed viral loads, mostly due to undiagnosed HIV infection and failure to link or retain diagnosed patients in care.

The period of acute HIV infection is particularly problematic with respect to transmission of the disease. Acute HIV infection may have no signs at all or can present itself as a nonspecific viral illness within 2-6 weeks of infection. This is also the most infectious phase of the disease and is often undiagnosed. After exposure to HIV, it can take as many as 3-4 weeks for antibodies to be detectable. Advanced fourth-generation HIV tests (also known as “combo tests”) have been developed to detect HIV during the acute window period before antibody is detectable and during established HIV.

There has been a progressive shift toward earlier initiation of ART in patients with HIV infection. It is well recognized that the key to successful ART in maintaining viral suppression is adherence to the prescribed regimen. Evidence indicates that drug resistance and consequent loss of viral suppression occurs more frequently in individuals who initiate therapy later in the course of infection than in those who initiate ART earlier. Initiation of ART is now recommended for all HIV-infected individuals, regardless of CD4 cell count, to reduce the morbidity and mortality associated with HIV infection and to prevent HIV transmission. More than 25 antiretroviral (ARV) drugs in 6 mechanistic classes are approved for treatment of HIV infection. These include nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), a fusion inhibitor (FI), a CCR5 antagonist, and integrase strand transfer inhibitors (INSTIs). In addition, two drugs (pharmacokinetic [PK] enhancers or boosters) are used to improve the PK profiles of some ARV drugs. The initial ARV regimen for a treatment-naive patient generally consists of two NRTIs, usually abacavir plus lamivudine or tenofovir disoproxil fumarate plus emtricitabine, plus a drug from one of three drug classes: an INSTI, an NNRTI, or a PK-enhanced PI.

Pre-exposure prophylaxis (PrEP) should be considered for individuals who are HIV-negative and at very high risk for HIV infection. When taken every day, PrEP with the combination of tenofovir and emtricitabine has been shown to reduce the risk of HIV infection in people who are at high risk by >90%. A recent study also suggests that “on demand” PrEP is also effective; in this scenario, a drug dose is taken three times: 2-24 hours before anticipated unprotected sex, and then at 24 and 48 hours afterwards. This “on demand” regimen reduced HIV acquisition by nearly 90%.

Dr. Sheila Fallon-Friedlander

Infectious Disease 2016: Pediatric Infected Atopic Dermatitis

Dr. Sheila Fallon-Friedlander

Dr. Sheila Fallon-Friedlander

Dr. Sheila Fallon-Friedlander

A major aggravating factor associated with atopic dermatitis is the presence of microorganisms on the patient’s skin surface. S aureus and Streptococcus pyogenes can exacerbate chronic skin inflammation. S aureus can colonize the skin or the respiratory tract in healthy patients and become pathogenic under conditions such as skin barrier breakdown and diminished immunity. Atopic dermatitis patients are highly susceptible to staphylococcal skin infections. Studies have shown that between 80% and 100% of patients with atopic dermatitis have nasal or skin colonization by S aureus vs 5% to 30% in individuals without atopic dermatitis. First and second generation cephalosporins are suitable for treatment of patients infected with methicillin-susceptible S aureus and MRSA is best treated with clindamycin and trimethoprim/sulfamethoxazole. Antimicrobial therapy should be tailored on the basis of local resistance patterns. Streptococcal infections may be treated with clindamycin and cephalexin.

Eczema herpeticum, also known as a form of Kaposi varicelliform eruption caused by viral infection, usually with the herpes simplex virus (HSV), is an extensive cutaneous vesicular eruption that arises from pre-existing skin disease, usually atopic dermatitis. Children with atopic dermatitis have a higher risk of developing eczema herpeticum, in which HSV type 1 is the most common pathogen. Patients with this condition may be treated with acyclovir.

Eczema cocksackium may also occur in patients with atopic dermatitis. In one case series, 51% of patients diagnosed with Eczema cocksackium had a history of atopic dermatitis. This enterovirus-associated exanthem is characterized by fever, stomatitis of the oral mucosa, and a vesicular rash affecting the hands, feet, and occasionally the buttocks. About one-third of infants <1 year of age may also present with bullae. Symptoms are strikingly similar to eczema herpeticum caused by HSV type 1. Patients with eczema cocksackium have been successfully treated with wet wrap therapy and low-dose corticosteroids. Bleach baths are also effective for both killing of pathogens and decreasing inflammation.

 

Infectious Disease 2016: Zika

Dr. Theodore Rosen

Dr. Theodore Rosen

Dr. Theodore Rosen

Zika virus: what is relevant for dermatologists?

Zika virus disease is a disease caused by Zika virus that is spread to people primarily through the bite of an infected Aedes species mosquito. The most common symptoms of Zika are fever, rash, joint and muscle pain, headache and conjunctivitis. The illness is usually mild with symptoms lasting for several days to a week after being bitten by an infected mosquito. Once a person has been infected, he or she is likely to be protected from future infections. The virus was first discovered in 1947 and is named after the Zika forest in Uganda. In 1952, the first human cases of Zika were detected and since then, outbreaks of Zika have been reported in tropical Africa, Southeast Asia, and the Pacific Islands. A stream of recent case report studies as well as a small number of case control and cohort studies initially suggested an association between Zika and both microcephaly and Guillain-Barré syndrome.

In May 2015, the Pan American Health Organization issued an alert regarding the first confirmed Zika virus infection in Brazil and on February 1, 2016, the World Health Organization declared Zika virus a public health emergency of international concern. In April, 2016, the CDC concluded that Zika virus is, indeed, a teratogen, associated with microcephaly, intracranial calcification in the newborn, and other neonatal brain abnormalities. Cases have now been widely reported throughout Central and South America and the Caribbean. Puerto Rico has been especially hard hit, with nearly 700 confirmed cases to date, including 8 cases suspected of being transmitted sexually. Of the cases confirmed in the continental United States, all have been acquired during travel to regions where mosquito-borne Zika virus infection is prevalent. However, some projections suggest that competent mosquito vectors within the United States will acquire the virus and that s significant Zika epidemic could emerge this summer. For this reason, the FDA just approved for wide distribution a Quest Diagnostics Zika blood test based on RNA detection. Heretofore, the only approved tests (IgM-based ELISA and RT-PCR) were only offered by the CDC and CDC-approved regional laboratories.

The rash associated with Zika virus is maculopapular, either morbilliform or scarlatiniform. It starts on the face on the first day of illness and spreads all over the body. It begins to fade within 2-3 days and is gone completely within a week.

Dr. Sheila Fallon-Friedlander

Infectious Disease 2016: Pemphigus Syphiliticus

Dr. Sheila Fallon-Friedlander

Dr. Sheila Fallon-Friedlander

Dr. Sheila Fallon-Friedlander

Persistent sniffles and a rash? Pemphigus syphiliticus is a possible answer.

Congenital syphilis is increasing and it is important to be aware of symptoms in neonates. Mucosal features may include rhinitis that develops at 1 week and worsens. Mucus is initially clear then progressively purulent and blood stained. Mucous ‘patches’ are seen on palate and lips along with perioral and perianal condylomata. Cutaneous features include maculopapular eruption over buttocks and lower torso, palms, and soles; and bullous eruptions that mimic staphylococcal infection.

Dr. Theodore Rosen

Infectious Disease 2016: HPV

Dr. Theodore Rosen

Dr. Theodore Rosen

Dr. Theodore Rosen

How do we best protect patients with the new HPV vaccine?

Quadrivalent and bivalent vaccines aimed at preventing infection with this virus have been available since 2006 and 2007, respectively. They are highly effective in preventing HPV-related cervical, vulvar, vaginal and penile cancer; and the quadrivalent vaccine also prevents genital warts related to HPV 6/11. In February 2015, the Advisory Committee on Immunization Practices (ACIP) recommended 9-valent HPV vaccine as one of three HPV vaccines that can be used for routine vaccination of females and one of two HPV vaccines for routine vaccination of males. It has been shown to provide high and consistent protection against infections and diseases related to these types, with ∼90% of cervical and other HPV-related cancers and precancers potentially being avoided. Importantly, about 14% of HPV-associated cancers in females (approximately 2800 cases annually) and 4% of HPV-associated cancers in males (approximately 550 cases annually) are caused by the 5 additional types in the 9-valent HPV vaccine. The benefit of protection against the 5 additional types targeted by 9-valent HPV vaccination is mostly limited to females for prevention of cervical neoplasms. This is because only a small percentage of HPV-associated cancers in males is due to the 5 additional HPV types in the new nano-valent vaccine.

The ACIP recommendations state that 9-valent HPV vaccine may be used to continue or complete a series started with a different HPV vaccine product. In addition, available data show no serious safety concerns in persons who were vaccinated with 9-valent HPV vaccine after having received a 3-dose series of quadrivalent HPV vaccine at least 12 months earlier.

Dr. Theodore Rosen

Infectious Disease 2016: Syphillis

Dr. Theodore Rosen

Dr. Theodore Rosen

Dr. Theodore Rosen

It you see an eruption that you cannot classify, think about syphilis – it is on the rise!

Syphilis, a genital ulcerative disease caused by the bacterium Treponema pallidum, is associated with significant complications if left untreated and can facilitate the transmission and acquisition of human immunodeficiency virus (HIV) infection.

Additionally, historical data demonstrate that untreated early syphilis in pregnant women may result in perinatal death of the infant in up to 40% of cases and, if acquired during the 4 years before pregnancy, can lead to infection of the fetus in 80% of cases.

In 2000 and 2001, the national rate of reported primary and secondary syphilis cases was 2.1 per 100,000 people in the population, the lowest rate since reporting began in 1941. In 2014, a total of 19,999 primary and secondary syphilis cases were reported, and the national syphilis rate increased to 6.3 cases per 100,000 people, the highest rate reported since 1994.

The rise in the syphilis rate was primarily attributable to increased cases among men and, specifically, among gay, bisexual, and other men who have sex with men.

Although the primary chancre developing at the site of inoculation usually has typical and well-characterized features, there is a wide spectrum of cutaneous manifestations of secondary syphilis that can mimic those of other dermatoses.

This may be particularly evident in patients with HIV infection. Given the increasing incidence of syphilis among the immunosuppressed patient population, recognition of atypical cutaneous manifestations is critical for adequate management.