Toll-Like Receptor 2 and Its Relationship With Streptococcus in Psoriasis.

The authors present the immunopathologic findings of Toll-like receptor 2 in psoriasis. This novel work shows positive staining within the dermal capillaries in psoriatic lesions. Neither normal skin nor lesional skin in eczema showed similar staining. The authors postulate how the activation of this innate immune system reactant plays a significant role in psoriasis and show how it may be associated with a cascade of events that begins with streptococcus and ends with psoriasis.

Coma blisters sans coma.

Coma blisters (CBs) are self-limited lesions that occur in regions of pressure during unconscious states classically induced by barbiturates. We report a case of CBs sans coma that were histologically confirmed in a 41-year-old woman who developed multiple tense abdominal bullae with surrounding erythema following a transatlantic flight. Interestingly, the patient was fully conscious and denied medication use or history of medical conditions. A clinical diagnosis of CBs was confirmed by histopathologic findings of eccrine gland necrosis, a hallmark of these bulIous lesions.

A new paradigm in the treatment of kerions: treat the inflammation.

Kerions result from a massive delayed-type hypersensitivity reaction to a dermatophyte. Treatment traditionally has been directed primarily toward the dermatophyte. The authors propose, however, that inflammation should be the initial target oftreatment. Clinical findings and treatment outcomes for two patients with kerions, treated with short courses of anti-inflammatory agents, are presented. Earlier studies showing minimal effects with corticosteroid treatment of kerions may have had design flaws. The anti-inflammatory treatment of kerions is both safe and effective and permits the duration of therapy to be shortened dramatically.

A pentad of vancomycin reactions.

Vancomycin is used in the treatment of infections caused by gram-positive bacteria resistant to beta-lactam antibiotics. It is also used in the treatment ofenterococci, although this use has been limited due to resistance. The authors report the clinical and pathological presentations of 5 different vancomycin hypersensitivity reactions, including morbilliform eruption, erythroderma, acute generalized exanthematous pustulosis, linear immunoglobulin A bullous dermatosis, and toxic epidermal necrolysis. With the increased prevalence of beta-lactam-resistant bacteria, reliance on vancomycin continues to increase; thus, the recognition of reactions to this drug will be helpful in caring for patients who require this medication in the future.

A Novel Approach to the Treatment and Prevention of Alzheimer's Disease Based on the Pathology and Microbiology.

Utilizing the pathology and microbiology found in tissue from patients with documented Alzheimer's disease (AD), the pathogenesis of this fateful disorder has been made clear. Borrelia burgdorferi and Treponema denticola spirochetes enter the brain, mostly via neuronal pathways and the entorhinal circulation. These organisms easily pass through the blood-brain barrier and have an affinity for neural tissue. Once in the brain, the spirochetes make intra- and extracellular biofilms, and it is the biofilms that create the pathology. Specifically, it is the intracellular biofilms that are ultimately responsible for neurofibrillary tangles and dendritic disintegration. The extracellular biofilms are responsible for the inflammation that initially is generated by the first responder, Toll-like receptor 2. The hypothesis that arises from this work is two-pronged: one is related to prevention; the other to treatment. Regarding prevention, it is very likely possible that AD could be prevented by periodic administration of penicillin (PCN), which would kill the spirochetes before they made biofilms; this would prevent the disease and would not allow any of the above deleterious changes generated by the biofilms to occur. As regards treatment, it may be possible to slow or prevent further decline in early AD by administration of PCN together with a biofilm disperser. The disperser would disrupt the biofilm coating and enable the PCN to kill the spirochetes. This protocol could be administered in a trial with the control arm utilizing the current treatment. The progress of the treatment could be evaluated by one of the current blood tests that is semi-quantitative. The specific protocols are listed.

Cutaneous gummatous tuberculosis in a kidney transplant patient.

Cutaneous gummatous tuberculosis (TB) is an uncommon subtype of cutaneous TB that can be seen in notably immunocompromised individuals. We report a case of cutaneous gummatous TB in an immunosuppressed kidney transplant patient. A 60-year-old Cambodian woman presented with fever attributed to recurrent pyelonephritis while on immunosuppressive medications 7 months after kidney transplant. She underwent a bilateral native nephrectomy and was found to have peritoneal nodules, which revealed caseating granulomas and acid-fast bacilli (AFB) consistent with kidney and peritoneal TB. Anti-TB therapy was initiated, resulting in symptom resolution. Subsequently, the Tuberculosis Control Program at the Department of Health (Philadelphia, Pennsylvania) discontinued her medications due to severe thrombocytopenia. During this time, she was closely monitored with blood draws. Approximately 10 weeks after treatment initiation, she noted recurrent fever and a painful, dull red, subcutaneous nodule on the right side of the flank. Biopsy showed an inflammatory infiltrate within the deep dermis indicative of suppurative granulomatous dermatitis. Ziehl-Neelsen stain demonstrated rare AFB within the cytoplasm of macrophages. The patient was restarted on anti-TB therapy resulting in the resolution of her fever and skin lesions. This case illustrates a noteworthy example of a rare form of cutaneous gummatous TB, which should be considered and included in the differential for cutaneous lesions in an immunosuppressed patient.

Lichenoid and other clinical presentations of atopic dermatitis in an inner city practice.

Atopic dermatitis (AD) has many different clinical presentations. In our inner city practice, we have observed a variant of AD in our heavily pigmented patients that we have termed lichen planus-like atopic dermatitis because of its clinical similarity to lichen planus. Clinically, this variant may be distinguished by the presence on extensor surfaces and a more rapid response to treatment. Histologically, in lichen planus-like AD, a spongiotic dermatitis is present; further, there is no lichenoid dermatitis evident. We compare this presentation with the others seen over an eight-month interval in our practice. We report on a lichen planus-like variant of atopic dermatitis in our African American patients. A limitation to this report is the relatively small sample size. Facial/extensor is the most common presentation of atopic dermatitis in our predominantly minority clinic.

Lichen planus-like atopic dermatitis: expanding the differential diagnosis of spongiotic dermatitis.

Spongiotic dermatitis represents a commonly encountered histopathological pattern seen by dermatopathologists. The differential diagnosis of lymphocyte predominant acute spongiotic dermatitis typically entails atopic dermatitis (AD), contact dermatitis, nummular dermatitis, pityriasis rosea and seborrheic dermatitis. Recently, our group has characterized a distinct subtype of spongiotic dermatitis occurring exclusively in heavily pigmented patients. Clinically, lesions of this subtype are nearly indistinguishable from lichen planus. However, the histology is contradistinctive to classic lichen planus. The purpose of this report is to raise awareness among dermatopathologists of this variant as a possible diagnosis in spongiotic dermatitis specimens submitted as lichen planus.

Psoriasis, chronic tonsillitis, and biofilms: Tonsillar pathologic findings supporting a microbial hypothesis.

Group A Streptococcus has been identified as a possible etiologic agent in psoriasis in epidemiologic, immunologic, immunopathologic, medical, and surgical studies. Tonsillectomy has been shown to provide considerable relief to 75% of patients with plaque psoriasis. Even with the substantial evidence supporting group A Streptococcus as a causative pathogen in psoriasis, it is an elusive pathogen because it is not culturable, nor does it exhibit any positive serologic evidence of its presence. One possible reason for the negative cultures and negative serology findings with group A Streptococcus is the development of biofilms. We conducted a pathologic study to determine whether biofilms were present in the tonsillar tissues of 10 patients with psoriasis-6 men and 4 women, aged 25 to 64 years (mean: 48)-and in 10 age- and sex-matched controls with chronic tonsillitis who did not have psoriasis. We found that biofilms were present in every tonsillectomy specimen we examined, including those of the controls. Whereas psoriasis has been considered a "double hit" phenomenon, we believe that the development of skin lesions is likely attributable to the presence of the gene PSORS together with the biofilm in psoriasis patients rather than to the biofilm itself. Biofilms have been identified in both extra- and intracellular locations. We believe our findings add further evidence supporting a microbial pathogenesis of this disease.

Alzheimer's Disease: Assessing the Role of Spirochetes, Biofilms, the Immune System, and Amyloid-ß with Regard to Potential Treatment and Prevention.

Alzheimer's disease (AD) is an infectious disease caused by spirochetes, and these spirochetes form biofilms, which attract the innate immune system. The innate immune system first responder, Toll-like receptor 2, generates both NF-κB and TNF-α which try to kill the spirochetes in the biofilm, but cannot penetrate the "slime". NF-κB is also responsible for the generation of amyloid-ß (Aß) which itself is anti-microbial. Aß cannot penetrate the biofilm either, and its accumulation leads to destruction of the cerebral neurocircuitry. Treatment with penicillin (as in tertiary syphilis, the comparator to AD) is outlined; a biofilm dispersing agent may need to be added to the protocol.

The presence and impact of biofilm-producing staphylococci in atopic dermatitis.

IMPORTANCE: Atopic dermatitis (AD) is thought to be a double-hit phenomenon with an unknown environmental component and a genetic abnormality likely centered on the filaggrin gene. Biologically, the presence of Staphylococcus aureus in AD was reported more than 2 decades ago, but the relationship to AD has been elusive. OBJECTIVE: To explore the bacteria that produce the biofilms in the lesions of AD and the response of the innate immune system to these biofilm occlusions of the sweat ducts by specifically evaluating Toll-like receptor 2. DESIGN, SETTING, AND PARTICIPANTS: University hospital dermatologic clinic study involving the environmental component related to the characterization, correlation, and impact of staphylococci and their biofilms in AD. We processed routine skin swabs from lesional and nonlesional skin from 40 patients with AD and performed scrapings and biopsies. We also obtained 20 samples from controls (10 inflamed skin samples and 10 normal skin samples). EXPOSURES: Gram staining, bright-field microscopy, hematoxylin and eosin, periodic acid-Schiff, Congo red, and light microscopy. MAIN OUTCOMES AND MEASURES: Association of staphylococcal biofilms with AD pathogenesis. RESULTS: All AD-affected samples contained multidrug-resistant staphylococci, with S aureus (42.0%) and Staphylococcus epidermidis (20.0%) as the predominant species. All isolates were positive for extracellular polysaccharide and biofilm (85.0% strong biofilm producers and 15.0% moderately to weakly positive). Polymerase chain reaction revealed the biofilm-mediating icaD (93.0%) and aap (12.5%) genes in the isolates (some contained both). We also examined tissues for microbial identification, extracellular biomass formation, biofilm formation, and staphylococcal biofilm in skin tissues. Occlusion of sweat ducts with periodic acid-Schiff-positive and Congo red-positive material was noted on microscopic tissue examination. Toll-like receptor 2 was shown to be activated in AD lesional skin (immediately proximal to the sweat ducts), which likely led to the initiation of proteinase-activated receptor 2-mediated pruritus and MyD88-mediated spongiosis. CONCLUSIONS AND RELEVANCE: Biofilm formation by AD-associated staphylococci almost certainly plays a major role in the occlusion of sweat ducts and leads to inflammation and pruritus. We believe the environmental hit in AD relates to staphylococci and their biofilms, which occlude sweat ducts.

The oldest new finding in atopic dermatitis: subclinical miliaria as an origin.

IMPORTANCE: In 1947, Sulzberger and colleagues published a micrograph of a blocked acrosyringium in a patient with atopic dermatitis (AD), believing that it had a large role in the disease process. Lacking appropriate probes, they could not confirm the finding. OBJECTIVE: To confirm the observations by Sulzberger et al on the blockage of sweat ducts in AD in pathologic specimens. DESIGN AND SETTING: Biopsy specimens diagnostic of various inflammatory diseases and with a secondary differential diagnosis of eczema were evaluated at an academic medical center. EXPOSURES: Evidence of ductal obstruction in each specimen was examined following staining with hematoxylin-eosin, periodic acid-Schiff, and Gram stain. MAIN OUTCOMES AND MEASURES: Comparison of biopsy specimens with control specimens and additional controls consisting of noninflamed skin. RESULTS: Using 36 biopsy specimens, this study confirmed the observations by Sulzberger et al on the blockage of sweat ducts in AD. Blocked acrosyringia were noted in each specimen on routine staining with hematoxylin-eosin. The study also confirmed the findings by earlier investigators about the blockage of sweat ducts in miliaria, showing eosinophilic material in the ducts that was positive for periodic acid-Schiff. Previous researchers also observed bacteria in the blockages, and this study demonstrated the same findings in AD, rather than miliaria. CONCLUSION AND RELEVANCE: Subclinical miliaria may be the earliest change in AD and likely initiates the process that causes intense pruritus.

Purple-red papules on foot.

An 88-year-old Caucasian man of Italian ancestry came into our clinic with multiple, painful purple-red "growths" on his left foot that he'd had for several years. The patient had no systemic complaints (no fever, chills, weight loss, night sweats). He had a history of hypertension, a cardiac valve replacement, and chronic back pain (secondary to a motor vehicle accident). He was taking warfarin and nadolol. The patient had multiple, 0.1- to 0.5-cm purple-red papules and nodules on the dorsal and plantar surfaces of the left foot, with associated moderate lower extremity edema and mottled dyspigmentation. We did a punch biopsy, which showed a nodular neoplasm composed of moderately plump, spindle-shaped cells in short interweaving fascicles and numerous extravasated erythrocytes in the spaces ("vascular slits") between the spindle-shaped cells. What is your diagnosis, and how would you manage this condition?