Erythematous Nodules on left dorsal hand and left wrist (almost sporotrichoid)
Central crusting
Punch biopsy was obtaned from dorsal wrist as well as tissue for culture for bacterial, fungal and acid fast bacilli
Ulceration with dense inflammation in the dermis
Suppurative and fibrinopurulent inflammation and hemorrhage centrally
Start to see larger cells and unusual intracytoplasmic sturctures on higher power
Characteristic morula or soccer ball forms
Characteristic thick walled organisms here with spores forming morula forms (“soccerball” or mulberry forms
Pas stain highlights these organisms
Soccer ball or mulberry forms
On Imuran and systemic corticosteroids
Large area of cellulitis with Centrally Necrotic and purpuric eschar
Eschar with edema and necrosis
Punch biopsy showing hemorrhage and inflammation with some overlying epidermal ulceration
Areas of suppuration
Thick walled organsims with non septate on pas stain
Right angle branching
Broad non septate hyphae (often ribbon like)
Soccer ball or mulberry forms
Broader hyphae with more collapsed and twisted look Unlike aspergillus which are narrower with septations and acute angle branching
PE: Multiple ulcerated coalescing plaques with yellowish-brown crust and surrounding erythema right leg
Notice how some lesions had a yellow exudate while others more black brown
Patient had a skin biopsy performed for histology and culture (fungal, bacterial, and acid fast bacilli) r/o infectious vs carcinoma vs stasis ulcer Overlying ulceration with superficila inflammation as well as a deeper focus of inflammation
Focusing on the superficial ulcer
Coating of fibrinopurulent material
Numerous fungal organisms- almost two morphologies present Small slender organisms Larger yeast and hyphal forms
Deeper focus
Larger oval organsims with septations
Organisms stain here with gMs silver stain
Larger organisms here with oval morphology
Smaller narrower organisms
Deeper focus here are larger organisms
2 organisms cultured 1 creamy white colonies 1 pigmented dark black colonies Note similarity to patients clinical lesions
Mycelia and conidia
Hand grenades Consistent with alternaria species
Solitary or grouped crusted papules and plaques Subcutaneous nodules Vegetating tumors Multiple ulcerations
10- 15 um (wider than aspergillus and fusarium) but less than mucormycosis (6 to 50 um) Relatively little branching, occasional acute angle branching
widespread molluscum like lesions with fever
Some follicularly based
Widespread over trunk
Umbilicated papules (molluscoid)
Dermatology consult called to evaluate and cutaneous lesions Skin biopsy was performed and portions sent for bacterial, mycobacterial, and fungal culture Patient begun on broad spectrum antibiotics and antifungals (IV Amphotericin B) Patient consented for HIV test Dense nodular infiltrate throughout the dermis
Suppuration and granulomatous inflammation
Parasitized histiocytes
There are numerous PAS positive organisms within histiocytes and freely within dermis
Dimorphic fungus At 37 ˚ C, Colony grows as yeast which reproduces by fission (helps to differentiate from H. capsulatum ) At 25 ˚ C, Colonies on Sabouraud agar usually velvety gray to white with radial folds (inhibited by cycloheximide) Culture often develops yellow-green to brown areas with characteristic diffusing red pigment Conidia resemble “skeleton hands” or “broomsticks” microscopically
Yeast forms budding by septation at 37 C
Conidia with broomstick appearance or skeleton hands
Patient’s culture confirmed diagnosis of disseminated penicilliosis Patient’s symptoms and skin lesions resolved quickly with antifungal therapy in two weeks Patient remained on maintenance itraconazole and was also begun on HAART
Penicillium chrysogenum used to produce the antibiotic penicillin Fleming discovered penicillium
P. marneffei has a restricted geographical distribution as seen in other dimorphic fungi such as Coccidioides , Paracoccidioides , and Blastomyces . Though the fungus was initially isolated from the bamboo rats and has also been recovered from internal organs of bamboo rats, the rodents are unlikely to be important in the transmission of the disease in nature and to humans. Penicilliosis marneffei has been classified as a geoanthromycosis: the fungus probably exists as a saprophyte in the environment (e.g. in the soil), and humans, as well as bamboo rats, are infected through inhalation of the conidiophores. This postulation, however, has not been proven beyond doubt A recent history of occupational or other forms of exposure to soil is also a significant risk factor. Importantly, exposure to or consumption of bamboo rats, was not a risk factor for infection. The exact mode of transmission of the fungus its natural habitat is still unsettled at the moment. The route of transmission and infection of P. marneffei is unknown at the moment. However, it is generally believed that inhalation of the conidia is a likely route, in line with the mode of infection for other moulds. The attachment of P. marneffei conidia to host cells and tissues is the first step in the establishment of an infection. The conidia-host interaction may occur via adhesion to the extracellular matrix protein laminin and fibronectin via a sialic acid-dependent process. Underlying immunosuppression can be found in 80% patients. The most frequent underlying disease is advanced HIV/AIDS Average CD4 count : 67 Infections in non-HIV-infected patients have been primarily among immunocompromised patients and less frequently in patients without any known underlying diseases.
Fever – nearly 100% patients Weight loss and anemia – 70% Pulmonary symptoms / cough – 50% Lymphadenopathy – 52% Hepatomegaly – 44% Splenomegaly – 23% Cutaneous lesions– 70% Mucocutaneous – 26% Predisposing factors besides AIDS: Alcoholism, TB, Hodgkin’s, immunosuppressive therapy, lymphoproliferative disorders, SLE, poor nutrition May occur rarely in immunocompetent patients May be localized or disseminated diseaseDisseminated disease: more common Similar to disease in AIDS patients Has been reported to occur even in immunocompetent patients Localized disease: rare Reported presentations: TB-like illness with cavitary pneumonia Solitary pulmonary nodules Osteomyelitis Superinfected lesions
Granulomatous Reticuloendothelial organs Immunocompetent Granulomas with yeast within histiocytes and multinucleated giant cells Suppurative Lung, subcutaneous tissue, and skin Immunocompetent Anergic Lung, liver, and skin Immunocompromised Necrotizing reaction with focal necrosis surrounded by diffuse infiltration of histiocytes engorged by proliferating yeast
The clinical and histologic picture was inconsistent with rhinoscleroma caused by a Klebsiella bacillus which usually causes a disfiguring nasopulmonary infection It was also inconsistent with granuloma inguinale which usually presents as a genital ulceration with exuberant granulation tissue This left the other four possibilities which were evaluated with special stains for AFB, Fungi, and Leishmania (Fite, Giemsa, and GMS) The special stains suggested a diagnosis of cutaneous peniciliosis which was also confirmed by the culture.
Histoplasmosis Difficult to grow with slow rate of growth Penicillium easily cultured with rapid rate of growth Yeast forms relatively indistinguishable at 37 c Mold forms at 25 C quite different Histoplasma Colonies on Sabouraud agar usually white (inhibited by cycloheximide) Culture often turns tan with age Penicillium Colonies on Saburaud agar usually velvety gray to white with radial folds (inhibited by cycloheximide) Culture often develops yellow-green to brown areas with characteristic diffusing red pigment
At 25 C mold forms – Thick walled round tuberculate conidia of histoplasma resemble “sea mines” microscopically Conidia of penicillium resemble “skeleton hands” or “broomsticks” microscopically
W/u for recent weight loss, fatigue , and anemia
Multiple discrete shiny papules with surrounding hyperpigmentation
Large eosinophilic deposits expanding the papillary dermis with a surrounding collarette
Evidence of surface irritation
Very pink and homogenous material
Admixture of inflammatory cells
Atypical hyperchromatic plasmacytoid cells
Congo Red and Crystal violet stains were negative Material strongly pas positive
Also positive for Kappa light chain immunohistochemical stain, negative for lambda
Strongly dif + for Igm
Transepidermal elimination, ulceration and crusting can occur Lipoid proteinoisis and epp usually not nodular deposits , usually around vessels and arranged perpendicular to epidermal surface Different ultrastructure
Bilateral malar areas – speckled blue black areas with slight erythema
Pigmented colloid milium
Pigmented colloid milium – caviar papules
Phenol used in leg ulcers Picric acid in burns Both now abandoned
28-35 % of south african blacks
Groin with confluent round to gyrate pink to red plaques with exfoliative white-tan scale
Distal extermities also w/ erythematous circular plaques with erosion and scale
Confluent circular plaques
Lower extremities, more confluent erythema with fine scale
Peeling and fissuring of soles with tan-brown scale
Backs of extremities. –craquelee like exfoliative plaques with adherent tan-brown scale
Atrophic glossitis, fissuring angular cheilitis
Psoriasiform epidermal hyhperplasia
Psoriasiform hyperplasia with pallor and overlying confluent scale-crust
Pallor and vacuolization of upper epidermis with edema in superficial dermis
Vacuolization with parakeratotic scale-crust
Mixed infiltrate with neuts, eos in dermis.
Another biopsy showed more subtle findings with slight hyperplasia, spongiosis and areas of abrupt confluent parakeratosis
Abrupt parakeratosis
Another area with abrupt parakeratosis
Islet cell tumor – alpha cells - glucagon
Papular hyperpigmeted eruption with widespread induration
Indurated hyperpigmented areas on back
Leonine facies with supraorbital thickening
Fine
Donut sign
Nodular and diffuse process in dermis
Nodule in upper dermis
Associated fibrosis and interstitial mucin
Mucin stain shows marked deposits ofmucin within dermis
Multiple erythematous plaques on extremities
Yellowish hue
Also had xanthelasma like lesions periorbitally
Bilateral exudative and crusted ulcerative plaques radial aspect of both hands
Patient had a skin biopsy performed for histology and culture (fungal, bacterial, and acid fast bacilli) Dense diffuse inflamamtory infiltrate with hemorrhage and overlying irregular hyperplasia
Dense infiltrae of neutrophils
No definitive vasculitis Special stains negative for afb, fungi, bacteria
Classical pG usually deepr ulcers with overhanging borders on lower extremities
PE: 10 x 9 cm slightly indurated square shaped hyperpigmented plaque with a 3 x 3 cm area of ulceration
First biopsy taken approximately 3 months after onset of lesion Submitted clinical data: r/o allergic contact, r/o fixed drug, r/o Lyme
Given the clinical history, the first biopsy was initially read as an interface dermatitis with features c/w a fixed drug eruption
Make note of how important a punch biopsy is. Second biopsy taken approximately 6 months later Submitted clinical data: fixed drug r/o other
Increased use of fluoroscopy guided interventional procedures since 1990’s Coronary artery stenting and angioplasty Transjugular intrahepatic portosystemic shunt placement (TIPS) Cardiac catheter ablation Chemotherapy catheter placement Percutaneous cholangiography Embolization procedures
Subsequent report in 1998 by Stone e t al described characteristic histologic features in patient who underwent coronary artery stenting under fluoroscopy Patient developed localized skin eruption on back at site of radiation approximately 7 days after procedure Oval to square shaped area of Erythema on left mid back with desquamation, painful Resembles fixed drug eruption clinically in early stages bx showed interface dermatitis Initial area of erythema became indurated and showed poikilodermatous changes clinically Subsequent biopsy seven months later showed changes of chronic radiation dermatitis
Immunohistochemical studies on the infiltrate T-lymphocytes Majority were CD8 (+) Lymphocytes infiltrating into epidermis also TIA-1 (+), a protein in cytotoxic lymphocytes and natural killer cells that triggers apoptosis in target cells Authors suggested that radiation may induce antigenic changes in keratinocytes leading to autoimmune attack by cytotoxic lymphocytes and subsequent apoptosis
FDA threshod absorbed dose in skin of 2 rad/min (0.02 Gy,min) and 20 rad/min (0.2 Gy/min) of areas of skin irradiated by a stationary continuous fluorscopic beam Screening for pre-existing conditions Patients with genetic predisposition (ataxia-telangiectasia) Diabetes mellitus Connective tissue disease (SLE, SCL, MCTD)
FDA threshod absorbed dose in skin of 2 rad/min (0.02 Gy,min) and 20 rad/min (0.2 Gy/min) of areas of skin irradiated by a stationary continuous fluorscopic beam Screening for pre-existing conditions Patients with genetic predisposition (ataxia-telangiectasia) Diabetes mellitus Connective tissue disease (SLE, SCL, MCTD)
3x 3 cm distal left leg ulcer with non undermined border DP pulses on left foot were not palpable Patient had a skin biopsy performed for histology and culture (fungal, bacterial, and acid fast bacilli),
Focal granulation tissue with white to yellowish film in other area r/o vasculitis, carcinoma, infection, stasis ulcer, pyoderma gangrenosum Patient had a skin biopsy performed for histology and culture (fungal, bacterial, and acid fast bacilli),
Our case demonstrated a more lobular proliferation than that seen in previous cases
At the time of presentation, brown-black hyperkeratotic , hyperlinear, ridged, verrucous plaques were present over the extensor surfaces of the knees, elbows, and ankles. Similar plaques affected the flexural areas of the axilla, antecubital fossa, and popliteal fossa. (Fig )Yellow-brown, confluent, lichenified, and fissured hyperkeratotic plaques involved most of the palms and soles, with extension onto the dorsal aspects of the hands and feet. (Fig ) Polycyclic, psoriasiform, erythematous patches of variable size with annular scale involved sixty percent of the trunk and extremities. (Fig )Examination of the teeth, hair, and nails revealed no abnormal findings. A KOH from the leading edge of a scaly patch showed no fungal elements. A biopsy was taken from an annular, scaly patch on the left forearm.
Routine laboratory evaluation including a blood count, chemistry panel, and hepatic panel were within normal limits.
This is consistent with the fact that keratin 10 is not significantly expressed in acral skin and mutations in keratin 10 do not cause palmoplantar keratoderma
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