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DERMATOPATHOLOGY OF LIFE THREATENIGN

DISORDERSOmar P. Sangüeza, MDProfessor and Director of

DermatopathologyWake Forest University School of

MedicineWinston Salem, NC

RUSH BIOPSY

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SCAR DISORDERS (SEVERE CUTANEOUS ADVERSE REACTIONS)

• Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome),

• Steven Johnson syndrome (SJS)• Toxic epidermal necrolysis (TEN)• Stevens-Johnson/toxic epidermal

necrolysis overlap syndrome• AGEP has the lowest mortality of the

group.

(DRESS syndrome)• Rare reaction to certain medications.• It is a widespread skin rash with fever,

lymphadenopathy, and characteristic hematologic abnormalities such as eosinophilia, thrombocytopenia, and atypical lymphocytosis.

• Often complicated by potentially life-threatening inflammation of internal organs: the syndrome has about a 10% mortality.

• Treatment consists of stopping the offending medication and providing supportive care.

• Systemic steroids are commonly used as well but no controlled clinical trials assess the efficacy of this treatment

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DRESS POR HIDANTOÍNA

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Toxic epidermal necrolysis (TEN)

• Potentially life-threatening dermatologic disorder characterized by widespread erythema, necrosis, and bullous detachment of the epidermis and mucous membranes.

• Can result in exfoliation and possible sepsis and/or death.

• Mucous membrane involvement can result in gastrointestinal hemorrhage, respiratory failure, ocular abnormalities, and genitourinary complications.

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Etiology

• Drugs– Antibiotics– antiepileptic drugs– nonsteroidal anti-inflammatory drugs

(NSAIDs)– ampicillin, allopurinol, corticosteroids (topical

and systemic), and antiretroviral drugs • Infection • Idiopathic

AGEP• Over 90% of cases of AGEP are provoked by

medications, most often beta lactam antibiotics (penicillins, cephalosporins and quinolones). Other drugs that may cause AGEP include:– Tetracyclines– Sulfonamides– Oral antifungals, particularly terbinafine– Calcium channel blockers such as diltiazem– Hydroxycholoroquine– Carbamazepine– Paracetamol.

AGEP

• Is a rare skin reaction that in 90% of cases is related to medication administration.

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AGEP• Usually, starts on the face or in the armpits and

groin, and then becomes more widespread, but it is more prominent in skin folds and often, there is facial swelling.

• It is characterised by the rapid appearance of areas of red skin studded with small sterile pustules.

• May be associated with fever and malaise, but often the patient is not particularly unwell.

• It may last for one to two weeks and then the skin peels off, as it resolves.

PEAG EN FASE DESCAMATIVA

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Herpes virus• Herpes Simplex virus (HSV) and

Varicella Zoster virus (VZV) are DNA viruses, members of the Herpesviridaefamily.

• HSV-1 is classically known to cause oral lesions while HSV-2 causes genital lesions, however, there is a crossover.

Varicella zoster virus• Varicella zoster virus is a unique member of

the herpesviridae family because it can cause two clinically distinct diseases

• Varicella primarily occurs in children with over 90% of infections occurring in children less than 10 years old

• Herpes Zoster is the other clinical manifestation of VZV which is more common in the elderly and immunocompromisedpatients.

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HERPES SIMPLEX IN HIV (+)

• Persistent herpetic infections:

Lesions of herpes simplex with no tendency to healing and poorly responsive to therapy: Suspect HIV infection.

• Herpetic folliculitis:

Persistent keratotic follicular lesions, often misdiagnosed aswarts: Suspect HIV infection.

• Genital herpetic ulcers:

Persistent genital or perianal ulcers: Suspect HIV infection.

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VHS-1

HERPES SIMPLEX

Kaposi’s varicelliform eruption (eczema herpeticum)

•Widespread cutaneous infections by HSV. •May also appear with other viral infections.•Usually: Localized vesiculous eruption followed

by disseminated lesions.•More frequent during primary HSV infections.•In patients with atopic dermatitis, Darier disease,

ichthyosis, mycosis fungoides, etc.

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VHS-1

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VARICELLA / ZOSTER

• VZV: Virus of the family Herpesviridae.

• Specific for human beings:

- Primary infection: Varicella.

- Latency

- Clinical reactivation: Herpes zoster

VARICELLA / ZOSTER

Varicella in immnunosuppressed patients:

• Longer disease• More systemic complications: Pneumonia, hepatitis, NCS

involvement.• Hemorrhagic lesions and abdominal pain• Higher mortality in:

- Children with hematologic malignancies or solid tumors- HIV+

• Before antiviral therapy: 32-50 % disseminated varicella,20 % pneumonia, 7-17 % death

Mucormycosis

• Group of diseases produced by members of the Mucorales order.

• The most common species associated with human infection are:– Rhizopus– Mucor– Absidia

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Aspergilosis

• Produced most commonly by the opportunistic fungi Aspergillus flavus.

• Primary cutaneous infection can occur when the skin is traumatized.

• Secondary infection of the skin occurs by hematogenous spread after colonization of the upper or lower respiratory tracts.

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Fusarium

• The organisms are ubiquitous and are found more commonly in the soil and are important pathogens for plants. – F. solani– F. oxysporum– F. moniliforme

Infection for Fusarium• Superficial skin lesions• Keratitis• Onychomycosis

• Deep and disseminated lesions produce ecthyma gangrenosum like lesions in the skin.

• Fever, positive blood cultures, sever myalgias, ocular symptoms and systemic symptoms.

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Candidiasis

• Mucocutaneous• Chronic Mucocutaneous

candidiasis• Systemic

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Protothecosis• Prototheca es un mutante aclorofilico de la alga

verde Chlorella. El organismo se encuentra diseminado en el medio ambiente, particularmente en lugares humedos. La infeccion ocurre usualmente como resultado de la inoculacion cuando el paciente se pone en contacto con agua contaminada. No existe transmision de persona a persona. Sin embargo, ha sido aislada de las uñas y otros sitios cutaneos en pacientes sanos.

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Graft vs. Host disease

• Transplanted organ contains immunocompetent cells

• Tissue antigens of the host are different from the donor

• The recipient is immunocompromised.

Pathogenesis of graft vs host disease

• Physiopathology– GVHD is initiated by the donor T-cells, which

react against the antigens present in the recipient cells. The activation of the T-cells and the damage produced to the tissues cause the liberation of cytokines which produce the clinical manifestations.

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Graft vs host disease.

• Acute– It is produced during the first 3 months after

the transplant and affect mainly skin, GI tract and liver.

• Chronic– Lesions are produced after 100 days and

affect mucosa, liver, muscle, peripheral nervous system and lung.

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Coma bullae

• Lesions that occur in the setting of a variety of neurological diseases. Although most commonly associated with barbiturate overdose, they can be seen in the setting of coma due to other etiologies.

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Coma bullae

• Hypoxia and external pressure seem to be pivotal factors.

• Blisters usually develop within 48–72 h after the onset of unconsciousness and tend to occur in pressure sites.

• Self-limited lesions that heal spontaneously over 1 or 2 weeks.

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Purpura fulminans

• Rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin that is rapidly progressive and is accompanied by vascular collapse and disseminated intravascular coagulation.

Purpura fulminans

• Neonatal• Idiopathic• Acute infectious.

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CryoglobulinemiasMonoclonal:Type I: Monoclonal IgG or Ig M

Mixed or polyclonal:Type II: Polyclonal IgG + Monoclonal IgMType III: Polyclonal IgG + Polyclonal IgM

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Mixed cryoglobulinemias

Precipitates of two or more Igs of the serum or plasma by cooling. An Ig behaves as antibody against the other one, resulting in the formation of an immunocomplex. The most common immunocomplex is IgG-IgM.Associated diseases:- Infections: HVC, HVB, HIV- Autoimmune disorders: SLE, RA

Type II Cryoglobulinemia• Type II (mixed) cryoglobulins (MC) consist of a

monoclonal antibody which binds to the Fc portion of polyclonal IgG demonstrating rheumatoid factor activity.

• Cryoglobulins can cause disease through two mechanisms: occlusion or immune complex vasculitis. – Simple occlusion with minimal early inflammation and often

retiform purpura/necrosis develops when cryoproteins gel on cold exposure (Often seen in type I cryoglobulinemia).

– Immune complex deposition often leads to inflammatory hemorrhage with palpable purpura (Often seen in mixed cryoglobulinemia).

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PAS

CALCIPHYLAXIS

• In 1962, Selye was the first to coin the term calciphylaxis to characterize this disease

CALCIPHYLAXIS

• Chronic renal failure• obesity,• diabetes mellitus• hypercalcemia, hyperphosphatemia• Elevated calcium-phosphate products• Secondary hyperparathyroidism• Hypercoagulable states

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