lunes, 20 de septiembre de 2010

Case Nº4 - FJM

A 68-year-old woman was admitted to our hospital with
general fatigue, palpitation, shortness of breath and leg
edema. She was diagnosed as having rheumatoid arthritis
(RA) at age 59 years at another hospital. She had since been
treated with nonsteroidal anti-inflammatory drugs, gold sodium
thiomalate and steroids. When she consulted our hospital,
clinical classification was stage IV and class II, due to
the bilateral erosive arthritis in her hands, wrists, knees and
feet.

In 1996 (at age 62 years), pancytopenia, which might
have been induced by gold sodium thiomalate, gradually developed.
This medication was discontinued, but the pancytopenia
persisted. Over the subsequent year, findings on gastrointestinal
endoscopy and abdominal computed tomography
revealed contracted liver, splenomegaly and esophageal
varices. Laboratory data showed no antigens or
antibodies for hepatitis virus, or antibodies for mitochondria
or smooth muscle, with the exception of antinuclear antibody
(ANA). Esophageal variceal banding ligature was thus performed.
Physical examination demonstrated deformities of the bilateral
joint of the hands, wrists, and feet. Swan-neck, boutonniere
deformity and radial deviation at the wrists with
ulnar deviation of the digits were noted in both hands.
Respiratory and heart sounds were normal. The spleen was
palpable about 5 cm below the left costal margin. Slight pitting
edema was observed in the bilateral lower extremities.

Laboratory findings are shown in Table 1. Urinalysis was
within the normal range. Neutropenia and hypoproteinemia
worsened, and hypoalbuminemia at 2.0 g/dl was detected.
Elevated levels of total bilirubin and aspartate aminotransferase
were observed, and the Child-Pugh classification was C (10 points).
ANA was positive at a titer of 640 (homogenous
and speckled), but other antibodies were negative.
Abdominal computed tomography revealed contracted liver,
splenomegaly, ascites and enlarged serpiginous
splenic vein.






























During admission, oral prednisolone was discontinued
due to various infections, including bacterial pneumonia and
methicillin resistant Staphylococcus aureus (MRSA) colitis.
Subcutaneous administration of granulocyte colony stimulating
factor (three times a week) was thus performed, while
ascites was simultaneously treated with diuretics. Laparoscopic
liver biopsy was not performed due to marked ascites
and neutropenia. Liver dysfunction worsened gradually and
ascites became prominent. She developed
hepatic encephalopathy and died from hepatic failure
and emaciation on March 31, 2003. Autopsy was not permitted.

¿What is the diagnosis?

Needle autopsy of the liver confirmed chronic hepatitis, the lobular architectures were maintained, while part of the portal field exhibited fibrosis including piecemeal necrosis, and was invaded by inflammatory cells and numerous lymphocytes with plasma cells (Fig. 3A, 3B). Pathological findings were consistent with a diagnosis of chronic hepatitis, which appeared to be AIH, although inflammatory cell invasion was not severe. According to the criteria of the International Autoimmune Hepatitis Group (Table 3A, 3B), the patient scored 19 points based on laboratory findings, pathophysiological consequences and clinical course, and her condition was diagnosed as AIH.

Discussion
In 1924, Felty first called attention to five cases with a
triad of RA, splenomegaly and neutropenia (5). This combination
of disorders was designated Felty’s syndrome in a
subsequent report by Hanrahan and Miller (6). This syndrome
frequently induces extra-articular features including
liver involvement, while common hepatic abnormalities are
nodular regenerative hyperplasia, abnormal lobular architecture,
portal fibrosis and cirrhosis (7–11). Thorne et al reported
a tendency for patients with abnormal liver findings to
have a higher incidence of vasculopathy and Felty’s syndrome
patients should be screened for portal hypertension as
they have an increased likelihood of bleeding from esophageal
varices (9). Indeed, in this patient, esophageal varices
were observed. The most common liver involvement in patients
with Felty’s syndrome is nodular regenerative
hyperplasia (12, 13). Goritsas et al recommended that signs
of portal hypertension and/or intrahepatic cholestasis in RA
patients should alert the physician to the possibility of nodular
regenerative hyperplasia, even in the absence of Felty’s
syndrome (14). However, the cause of hepatic nodular regenerative
hyperplasia in patients with Felty’s syndrome remains
unresolved.
In the present case, contracted liver was thought to be
clinically liver cirrhosis based on blood test, abdominal computed
tomography and ultrasonography findings. However,
liver autopsy findings revealed chronic hepatitis. Histological
findings showed a basically normal architecture and
338 Internal
a partly piecemeal necrosis in the portal triad field, in addition
to infiltration of lymphocytes with plasma cells, which
suggested AIH.
AIH was first reported by Mackay et al in 1965. The characteristic
pathologic features were chronic active hepatitis
with piecemeal necrosis, lobular involvement, and bridging
necrosis with lymphocytes and plasma cells (15). The clinical
features were similar to chronic viral hepatitis. For diagnosis
of AIH, it was recently recommended to use the
scoring system of the International Autoimmune Hepatitis
Group (16). According this scoring system, the present patient
was diagnosed as having autoimmune hepatitis with a
score 19 points. Kaise et al reported that one in 49 patients
with Felty’s syndrome exhibits concomitant AIH (11). Based
on that report, it is certain that AIH in Felty’s syndrome is
extremely rare.

Minimum Required Parameter



















Aditional Parameters



















Splenomegaly in patients with Felty’s syndrome might be
due to expansion of the sinusoidal pulp, as indicated by
wider separation of the periarterial lymphoid sheaths and
hyperplastic germinal center (17). In the present case, we are
convinced that increasing blood flow to the spleen due to
splenomegaly caused portal hypertension, congestion of
blood within the liver, and chronic hepatitis gradually worsened
to liver failure.
The present patient had contracted liver disease of unknown etiology. Chronic hepatitis compatible with AIH was
diagnosed based on an international scoring system and the
pathological findings of needle autopsy respectively. In patients
with Felty’s syndrome, severe hepatitis is rarely observed
and correlations with the liver are difficult to confirm.
When treating Felty’s syndrome patients with severe liver
dysfunction, AIH should be considered. Inaba et al reported
a case in which the patient had been treated by prednisolone
for AIH and was diagnosed as having Felty’s syndrome (18).
This report raises the possibility that our patient had AIH when she was diagnosed with RA and prednisolone therapy suppressed the clinical features of AIH. Retracing the clinical course, liver dysfunction may have developed after steroid therapy was discontinued. If this was the case scenario, the response to therapy in this patient should, in fact, be considered as a relapse with a score of 21 points. In the present
patient, the most difficult point was that steroid therapy had
to be discontinued due to life threatening infections (MRSA
colitis, recurrent pneumonia) which might have been due to
neutropenia and steroid therapy. Interruption of steroid therapy
in this patient may have been a crucial event in the ultimate
clinical course.

Reference

- Felty’s Syndrome with Chronic Hepatitis and
Compatible Autoimmune Hepatitis: A Case Presentation

domingo, 12 de septiembre de 2010

Leishmaniasis - Fitzpatrick Review




Cutaneous leishmaniasis (CL) of Old World (OWCL) and New World (NWCL) types, characterized by development of single or multiple cutaneous papules at the site of a sandfly bite, often evolving into nodules and ulcers, which heal spontaneously with a depressed scar.

Mucosal leishmaniasis (ML)

Diffuse (anergic) cutaneous leishmaniasis (DCL)

Visceral leishmaniasis (VL); kala-azar; post–kala-azar dermal leishmaniasis (PKDL)

Life Cycle Leishmania dimorphic. In mammalian host: amastigote (leishmanial) form—2 to 3 m in length, oval/round, aflagellate; lives intracellularly in cells of reticuloendothelial system. In GI tract of sandfly/in culture: promastigote (leptomonad) form—10 to 15 m in length, spindle-shaped, flagellated; extracellular. Speciation: isoenzyme patterns, kinetoplast DNA buoyant densities, specific phlebotomine vectors, monoclonal antibodies, DNA hybridization, DNA restriction endonuclease fragment analysis.

Reservoir Varies with geography and leishmanial species. Zoonosis involves rodents/canines. Mediterranean littoral—dogs. Southern Russia—gerbils. For L. major, desert rodents. For L. tropica, rats. For L. infantum, wild canines, dogs; in endemic areas of Spain, up to 20% of dogs tested harbored parasites in skin and viscera.

Vector Female sandflies of genus Phlebotomus (Old World) and genera Lutzomyia (New World). Breed in cracks in buildings, rubbish, rubble; rodent burrows, termite hills, rotting vegetation. Weak fliers; remain close to ground near breeding site, Ingest amastigotes while feeding on infected mammals, converting to promastigotes in the gut of the sandfly; replicate in gut.

Transmission Promastigotes deposited on skin of host into a small pool of blood drawn by probing sandfly

The clinical and immunologic spectrum of leishmaniasis parallels that of leprosy. CL occurs in a host with good protective immunity. MCL occurs in those with an intense inflammatory reaction. DCL occurs with extensive and widespread proliferation of the organism in the skin but without much inflammation or tendency for visceralization. VL occurs in the host with little immune response and/or in immunosuppression. Unlike leprosy, extent and pattern are strongly influenced by the specific species of Leishmania involved. Additional factors that affect the clinical picture: number of parasites inoculated, site of inoculation, nutritional status of host, nature of the last non-blood meal of vector. Infection and recovery are followed by lifelong immunity to reinfection by the same species of Leishmania. In some cases, interspecies immunity occurs

OWCL

L. major

Asia, Africa, Europe in tropical and subtropical zones; Middle East (Iran, Iraq, eastern Saudi Arabia, Jordan Valley of Israel and Jordan, Sinai Peninsula). More common in rural areas. Begins as small erythematous papule, which may appear immediately after sandfly bite but usually 2 to 4 weeks later. Papule slowly enlarges to 2 cm over a period of several weeks and assumes a dusky violaceous hue (Fig. 26-29). Eventually, lesion becomes crusted in center with a shallow ulcer and raised indurated border = vulcano sign (Fig. 26-30). In some cases, the center of the nodule becomes hyperkeratotic, forming a cutaneous horn. Small satellite papules may develop at periphery of lesion, and occasionally subcutaneous nodules along the course of proximal lymphatics. Rarely, lesions become locally invasive and extend into subcutaneous tissue and muscle. Peripheral extension usually stops after 2 months, and ulcerated nodule persists for another 3 to 6 months, or longer. The lesion then heals with a slightly depressed scar. In some cases, CL remains active with positive smears for 24 months (nonhealing chronic cutaneous leishmaniasis). The number of lesions depends on the circumstances of the exposure and extent of infection within the sandfly vector. May result in multiple lesions, up to 100 or more (Figs. 26-30 and 26-31).

NWCL

L. mexicana Complex

Mexico, Central America, as far north as Texas, as far south as Brazil. Lesions develop in similar fashion to those caused by L. major. Small erythematous papule develops at sandfly bite site, evolving into ulcerated nodule (Fig. 26-32). Eventually lesion heals with a depressed scar. Enlarges 3 to 12 cm with raised border. Nonulcerating nodules may become verrucous. Lymphangitis, regional lymphadenopathy. Isolated lesions on hand or head usually do not ulcerate; heal spontaneously. Ear lesions may persist for years, destroying cartilage (chiclero ulcers)

L. braziliensis Complex

Clinical lesions similar to those of OWCL. Some strains can invade mucous membranes of mouth, nose, pharynx, larynx to cause MCL

Mucosal Leishmaniasis

Characterized by nasooropharyngeal mucosal involvement, a metastatic complication of CL. Caused by Viannia subgenus, typically L. (V.) braziliensis, L. (V.) panamensis, and L (V.) guyanensis. Mucosal disease usually becomes evident several years after healing of original cutaneous lesions; cutaneous and mucosal lesions can coexist or appear decades apart. Edema and inflammatory changes lead to epistaxis and coryzal symptoms. In time, nasal septum, floor of mouth, and tonsilar areas destroyed (Fig. 26-34). Results in marked disfigurement (referred to as espundia in South America). Death may occur due to superimposed bacterial infection, pharyngeal obstruction, or malnutrition.

Diffuse Cutaneous Leishmaniasis

Resembles lepromatous leprosy; large number of parasites in macrophages in dermis; no visceral involvement. In Old World, occurs in 20% of individuals with leishmaniasis in Ethiopia and Sudan. In South America, attributed to a member of L. braziliensis complex. Presents as a single nodule, which then spreads locally, often through extension from satellite lesions, and eventually by metastasis. In time, lesions become widespread with nonulcerating nodules appearing diffusely over face, trunk. Responds poorly to treatment.

Leishmaniasis Recidivans (LR)

Complication of L. tropica infection. Dusky-red plaques with active, spreading borders and healing centers, giving rise to gyrate and annular lesions. Most commonly affects face; can cause tissue destruction and severe deformity.

Post–kala-Azar Dermal Leishmaniasis (PKDL)

Sequel to VL that has resolved spontaneously or during/after adequate treatment. Lesions appear 1 y after course of therapy with macular, papular, nodular lesions, and hypopigmented macules/plaques on face, trunk, extremities. Resembles lepromatous leprosy when lesions are numerous. Develops in 20% of Indian patients treated for VL caused by L. donovani and in a small percentage of Ethiopian patients with VL caused by L. aethiopica.

Visceral Leishmaniasis

Can remain subclinical or become symptomatic, with acute, subacute, chronic course. Inapparent VL cases outnumber clinically apparent cases. Malnutrition is risk factor for clinically apparent VL. Bone marrow, liver, spleen are involved. Term kala-azar (Hindi for 'black fever,' some patients had gray color) refers to profoundly cachectic febrile patients with life-threatening disease. Patients present with fever, splenomegaly, pancytopenia, wasting.

Dermatopathology: Large macrophages filled with 2- to 4-m amastigotes (Leishman-Donovan bodies); mixed lymphocytic, plasmacytic infiltrate. In Wright- and Giemsa-stained preparations, the amastigote cytoplasm appears blue, nucleus relatively large and red; distinctive kinetoplast is rod-shaped and stains intensely red

Culture Novy-MacNeal-Nicolle medium at 22°C to 28°C for 21 days grows motile promastigotes – PCR

Course and Prognosis

CL

Whether caused by L. tropica or L. mexicana, CL is self-limited. Scarring is increased by secondary bacterial infection.

MCL

May extend to secondary sites. Superinfection common. Death from pneumonia.

DCL

Progressive; refractory to treatment; cures rare

No chemoprophylaxis for travelers exists

Lesional Therapy

Local injection of antimonials (Pentostam), usually at weekly intervals; up to 1 mg/kg may be injected in borders of lesions. Also cryosurgery, ultrasound-induced hyperthermia, excision, electrosurgery. Topical 15% paramomycin sulfate, 12% methylbenzethonium chloride in white paraffin twice daily for 10 days

Cutaneous Larva Migrans and Larva Currens

Ancylostoma braziliense is most common cause in central and southeastern United States. Other penetrating nematode larvae: A. caninum, Uncinaria stenocephala (hookworm of European dogs), Bunostomum phlebotomum (hookworm of cattle).

Ova of hookworms are deposited in sand and soil in warm, shady areas, hatching into larvae that penetrate human skin. Activities and occupations that pose risk include contact with sand/soil contaminated with animal feces: playing in sandbox, walking barefoot or sitting on beach, working in crawl spaces under houses, gardeners and plumbers, farmers, electricians, carpenters, pest exterminators.

Larva Currens

Filariform larvae of Strongyloides stercoralis can penetrate skin (usually on buttocks), producing similar lesions, i.e., larva currens

Humans are aberrant, dead-end hosts who acquire the parasite from environment contaminated with animal feces. Larvae remain viable in soil/sand for several weeks. Third-stage larvae penetrate human skin and migrate up to several centimeters a day, usually between stratum germinativum and stratum corneum. Parasite induces localized eosinophilic inflammatory reaction. Most larvae are unable to develop further or invade deeper tissues and die after days or months. Migration to viscera causes Loeffler's síndrome

Larva Currens

Caused by S. stercoralis. Papules, urticaria, papulovesicles at the site of larval penetration (Fig. 26-25). Associated with intense pruritus. Occurs on skin around anus, buttocks, thighs, back, shoulders, abdomen. Pruritus and eruption disappear when larvae enter blood vessels and migrate to intestinal mucosa


Treatment: Thiabendazole, orally 50 mg/kg per day in two doses (maximum 3 g/d) for 2 to 5 days; also effective when applied topically under occlusion. Ivermectin, 6 mg bid. Albendazole, 400 mg/d for 3 days; highly effective

Source - Fitzpatrick dermatology

sábado, 11 de septiembre de 2010

Rosacea - A fitzpatric review

Rosacea (40-50)

Females predominantly, but rhinophyma occurs mostly in males.

The rosacea diathesis: episodic erythema, "flushing and blushing"

Stage I: Persistent erythema with telangiectases.

Stage II: Persistent erythema, telangiectases, papules, tiny pustules.

Stage III: Persistent deep erythema, dense telangiectases, papules, pustules, nodules; rarely persistent "solid" edema of the central part of the face

Acne may have preceded the onset of rosacea by years; nevertheless, rosacea may and usually does arise de novo without any preceding history of acne or seborrhea.

Early

Pathognomonic flushing; tiny papules and papulopustules (2 to 3 mm), pustule often small (<1>No comedones

Late

Red facies and dusky-red papules and nodules (Figs. 1-5, 1-6, and 1-7) Scattered, discrete lesions. Telangiectases. Marked sebaceous hyperplasia and lymphedema in chronic rosacea, causing disfigurement of the nose, forehead, eyelids, ears, and chin

Distribution

Characteristic is the symmetric localization on the face (Fig. 1-7). Rarely, neck, chest (V-shaped area), back, and scalp

Rhinophyma (enlarged nose, Fig. 1-8), metophyma (enlarged cushion-like swelling of the forehead), blepharophyma (swelling of the eyelids), otophyma (cauliflower-like swelling of the earlobes), and gnathophyma (swelling of the chin) result from marked sebaceous gland hyperplasia and fibrosis. Upon palpation: soft, rubber-like.

Dermatopathology

Nonspecific perifollicular and pericapillary inflammation with occasional foci of "tuberculoid" granulomatous areas; dilated capillaries. Foci of neutrophils high and within the follicle. Later stages: diffuse hypertrophy of the connective tissue, sebaceous gland hyperplasia, epithelioid granuloma without caseation, and foreign-body giant cells.

DIferential Dx: Facial Papules/Pustules

Acne (in rosacea there are no comedones), perioral dermatitis, S. aureus folliculitis, gram-negative folliculitis, D. folliculorum infestation.

Facial Flushing/Erythema

Seborrheic dermatitis, prolonged use of topical glucocorticoids, systemic lupus erythematosus; dermatomyositis

Topical

Metronidazole gel or cream, 0.75%, twice daily—very effective

Metronidazole cream, 1%, once daily

Sodium sulfacetamide , sulfur lotions 10% and 5%

Topical antibiotics (e.g., erythromycin gel) are less effective.

Systemic

Oral antibiotics are more effective than topical treatment.

Minocycline or doxycycline , 50 to 100 mg twice daily, first-line antibiotics; very effective (doxycycline is a phototoxic drug and its use limits exposure to sunlight in summer).

Tetracycline , 1 to 1.5 g/d in divided doses until clear; then gradually reduce to once-daily doses of 250 to 500 mg.

A dose of 50 mg minocycline or doxycycline or 250 to 500 g tetracycline is given as maintenance.

Oral Isotretinoin

For individuals with severe disease (especially stage III) not responding to antibiotics and topical treatments. A low-dose regimen of 0.1 to 0.5 mg/kg body weight per day is effective in most patients, but occasionally 1 mg/kg may be required. (For side effects and precautions see Severe Acne




RINOPHYMA