Sarcoidosis

It is a chronic, multisystem disorder of unknown cause.

• chronic multisystem disease of unknown etiology, characterized by noncaseating (hard) granulomas and lymphocytic alveol,
• Sarcoidosis is a noninfectious, multisystem granulomatous disease of unknown cause, commonly affecting young and middle-aged adults.
• Almost any other organ may be involved, including liver, spleen, lymph nodes, heart, and CNS.
• Also can be diagnosed in asymptomatic patients with abnormal CXRs
• Frequently presents with hilar adenopathy, pulmonary infiltrates, ocular and skin lesions
• Systems affected: Primarily Pulmonary but also Cardiovascular; GI; Hematologic/Lymphatic; Endocrine; Renal; Neurologic; Dermatologic; Ophthalmologic; Musculoskeletal

Sarcoidosis Diagnosis Characterized by :

• · T Iymphocytes and phagocytes
• · Granulomas (non-caseating) in various organs.
• No definitive test for diagnosis, but diagnosis is suggested by the following:
• Clinical and radiographic manifestations
• Exclusion of other diagnoses
• Histopathologic detection of noncaseating granulomas

Organs most commonly involved:

• · Lung
• · Skin
• · Eye
• · Liver

Course of Disease may be

• · Acute ,
• · Sub-acute
• · Chronic.

Sarcoidosis Etiology

• · Cause unknown
• · Self-antigens may be responsible for disease
• · Disease is due to exaggerated cellular immune response.

Sex

• · Females may be more susceptible
• · Male: Female 1: 1, both sexes equally affected usually.

Age

• · Common between 20 – 40 years
• · Children and elderly can also be affected.

Sarcoidosis Pathophysiology and Immunopathogenes’s

• · Accumulation of CD₄ + TH11ymphocytes in or- gan
• · Granulomas
• Thought to be due to exaggerated cell-mediated immune response to unknown antigen(s)
• In the lungs, the initial lesion is CD4+ T-cell alveolitis, causing noncaseating granulomata, which may resolve or undergo fibrosis.
• · Multinucleated giant cells/Langhans giant cells
• · Schaumann bodies–Conch-like (Shankh)
• · Asteroid bodies.

Sarcoidosis Clinical symptoms

• · Systemic disease
• · Lungs involved-respiratory symptoms mainly
• · May be asymptomatic (discovered on chest x­ray)
• · May present abruptly (suddenly) or slowly in weeks or months
• · Usually at ages <40 yrs.
• If signs indicate Löfgren syndrome, it is not necessary to perform a biopsy because prognosis is good with observation alone, and biopsy would not change management.

Constitutional symptoms are present:

• · Fever, fatigue, anorexia (loss of appetite), weight loss.

Respiratory symptoms: Cough, Dyspnoea Retrosternal chest discomfort Polyarthritis Lofgren‘s syndrome:

• · Erythema nodosum
• · Bilateral hilar adenopathy
• · Arthritis of ankles, knees, wrists, elbows.

Heerfordt- Waldenstrom syndrome:

• · Fever
• · Parotid enlargement
• · Anterior uveitis
• · Facial nerve palsy.

Lungs

• · Interstitial lung disease
• · Alveoli, small bronchi, small blood vessels in- volved
• · There is dyspnoea, dry cough
• · There are dry rales in lungs
• · Hemoptysis may be present
• · Lung collapse can occur due to : – Endobronchial sarcoidosis
• – Pressure from enlarged lymph nodes
• · Wheezing may be present.

Necrotizing sarcoidal granulomatosis

• · Pulmonary artery – granulomatous arteritis
• · Pleural effusion – usually unilateral
• · Chronic pleural thickening
• · Pneumothorax
• · Hydropneumothorax.

Lymph node enlargement

• · Discreet
• · Firm
• · Rubbery
• · Painless.

Lymphadenopathy – (usually of hilar nodes)

• · Paratracheal lymph node
• · Mediastinal lymph node
• · Cervical
• · Axillary
• · Inguinal
• · Mesenteric
• · Retroperitoneal.

Skin

• · Erythema nodosum
• · Plaques
• · Subcutaneous nodules
• · Maculopapular eruptions
• · Lupus pernio – purple, swollen and shiny patches on nose, cheeks, lips, ears, fingers
• · Clubbing of fingers
• ·Polyarthralgias may occur with skin lesions. Resolves in 2 to 4 weeks.
• Skin lesions are usually seen on face-around eyes and nose, buttocks, extremities, back.

Eyes

• · Can cause blindness
• · Can involve uveal tract, iris, ciliary body, choroid, conjunctiva
• ·Blurred vision, photophobia.

Keratoconjunctivitis sicca syndrome

• • Dry, painful eyes.

Upper respiratory tract

• · Nasal stuffiness
• · Tonsil involvement
• · Tongue involvement
• ·Larynx.

Symptoms

• · Hoarseness of voice
• · Dyspnoea
• · Wheezing
• · Stridor
• · Even complete obstruction of passage.

Bone marrow / Spleen

• · Anaemia
• · Neutropenia
• · Eosinophilia
• · Thrombocytopenia
• · Splenomegaly.

Liver

• · Hepatomegaly
• · Usually mild features
• · Jaundice
• · Portal hypertension.

Kidney

• Rare involvement
• Granulomas produce 1, 25 dihydroxy-vitamin D which can lead to increased calcium absorption in the gut causing nephrolithiasis.
• Tubular, glomerular, renal artery disease can occur.

Nervous system

• · Seventh nerve involvement with facial paralysis sudden, transient (for short period)
• · Optic nerve dysfunction
• · Papilledema
• · Hypothalamic and pituitary abnormalities
• · Chronic meningitis
• · Granulomas (space occupying lesions)
• · Seizures
• · Peripheral neuropathy
• · Spinal disease.

Musculoskeletal system

• · Involvement of bones, joints, muscles
• · Swelling of digits
• · Arthritis
• · Deformities of joints
• · Polymyositis.

Heart

• • LVH
• .’ Arrhythmias
• · Conduction defects (CHB)
• · Sudden death
• · Papillary muscle dysfunction (PMD)
• · Pericarditis
• · CHF
• · Corpulmonale.

Endocrine and Reproductive system

• · Diabetes insipidus
• · Hypopituitarism
• · Addison’s syndrome,

Pregnancy

• · Patient may improve during pregnancy but wors­ens after del ivery.

Parotids involvement

• • Bilateral non-tender, smooth enlargement.

Gastrointestinal system (GIT)

• • Rare,

Death

• · Occurs due to respiratory disease
• · CHF,

Diagnosis Test —

Sarcoidosis INVESTIGATIONS

• Lymphocytopenia Increased ESR Hyperglobuli.nemia
• Increased ACE (angiotensin converting enzyme) lev­els,

Chest x-ray

• · Type I-
• · Type II
• bilateral hilar lymphadenopathy
• – bilateral hilar lymphadenopathy with parenchymal changes
• Type III – no hilar lymphadenopathy, only dif­fuse parenchymal changes
• Type I – acute, reversible
• Type Il, III – chronic, progressive

X-Ray findings

• · Egg-shell calcification of lymph nodes
• · Pleural effusion
• · Cavitation
• Collapse Pneumothorax Cardiomegaly
• Pulmonary hypertension changes,

Lung function tests

• · Decreased lung volumes
• · Airflow limitation,
• Gallium 67 lung scan
• • Diffuse uptake.
• Bronchoalveolar lavage (BAL)
  • • IncreasedCD₄+THl.

Sarcoidosis TREATMENT

• Therapy of choice is glucocorticoids : Prednisone­1 mg/kg for 4-6 weeks, tapered in 3 months.
• Others are:
  • Methotrexate – 5-15 mg/week single dose orally.
  • Indomethacin
  • Chloroquine
  • Pentoxifylline
  • Allopurinol
  • Levamizole
  • Azothiaprine
  • Cyclophosphamide
  • Cyclospori ne,
• There is spontaneous remission or cure in 50% of patients, However glucocorticoids may be given in symptomatic patients or patients with organ derange­ment,

First Line TREATMENT

• No treatment may be necessary in asymptomatic individuals, but treatment may be needed for specific indications, such as cardiac, CNS, or ocular involvement.
• ›Systemic therapy is clearly indicated for hypercalcemia, cardiac disease, neurologic disease, and eye disease not responding to topical therapy.
• ›Treatment of pulmonary and skin manifestations is done on the basis of impairment. The symptoms that necessitate systemic therapy remain controversial.
• Systemic corticosteroids in the symptomatic individual:
• ›If no relapse, 15–20 mg/d × 8–12 months
• ›If stable, taper by 5 mg/wk to 15–20 mg/d over the next 6 weeks
• ›Relapse is common.
• ›Usually prednisone initially, 40–60 mg/d × 1st 6 weeks
• Contraindications: Patients with known problems with corticosteroids
• In patients with skin or ocular disease, topical steroids may be effective.
• Precautions: Careful monitoring in patients with diabetes mellitus and/or hypertension
• Significant possible interactions: Refer to the manufacturer’s profile of each drug .

Second Line TREATMENT

• Azathioprine: 50–100 mg/d
• Cyclophosphamide: 25–50 mg/d, increasing to goal white blood cell (WBC) count of 4,000–7,000/mm³
• Hydroxychloroquine (Plaquenil): 100–400 mg/d
• Infliximab, a chimeric monoclonal antibody, has been useful in refractory cases. Dose is 3–5 mg/kg IV initially, 2 weeks later, then q4–6wk.
• Methotrexate: 10–15 mg/wk
• Thalidomide has been used for chronic skin lesions. The anti-tumor necrosis factor (TNF) agent infliximab also has been used in some refractory cases
• Use of immunosuppressants such as methotrexate or azathioprine will require regular monitoring of CBC and LFTs.