• Exam prep - University exams, NEET PG, FMGE concepts
• Clinical questions - Cases, diagnoses, management protocols
• Drug/pharmacology queries
• Anatomy, physiology, pathology topics
• Career guidance - PG entrance strategy, internship tips

• Short notes on any topic
• Important questions for a subject
• Case-based explanations
• Differentials and management protocols
• Quick revision of high-yield topics

---

🫁 SARCOIDOSIS - Complete Study Notes

---

1. DEFINITION

• Chronic, systemic disease of unknown etiology
• Characterized by noncaseating granulomas in one or more organ systems
• Lungs and lymphatic system are most commonly affected
• Clinical picture: asymptomatic → multi-organ failure

---

2. EPIDEMIOLOGY

---

3. ETIOLOGY

• Exact cause unknown
• Exaggerated cellular immune response as etiological factor
• Triggered by antigens - both infectious (Mycobacterium tuberculosis, atypical mycobacteria, viruses, fungi, protozoa, pollen) and non-infectious
• Exogenous agent → immunologic sensitization by acting as a "hapten"
• Beryllium can produce an identical illness in humans
• Recent workers found evidence of mycobacterial DNA in sarcoid tissue
• Recurrence occurs in transplant recipients - suggesting a transmissible agent
• Genetic factors also play a role

---

4. PATHOGENESIS

• Unknown antigen triggers cell-mediated immune response
• First manifestation: accumulation of CD4+ T lymphocytes and mononuclear phagocytes in affected organs
• Followed by formation of noncaseating granulomas - aggregation of macrophages, epithelioid cells, multinucleated giant cells
• Organ dysfunction results from granulomas + accumulated inflammatory cells distorting tissue architecture
• Chronic inflammation → fibrosis and permanent damage
• Hypercalcemia: Vitamin D analogs produced by activated macrophages → nephrolithiasis, nephrocalcinosis → chronic kidney disease

---

5. CLINICAL MANIFESTATIONS

General

• Fever, malaise, weight loss, night sweats (resemble TB)

Respiratory (Most Common - 90%)

• Pulmonary involvement on chest X-ray
• Upper lobes > lower lobes
• Dyspnea, cough, crepitations on auscultation
• Severe: irreversible fibrosis and honeycombing
• Extrapulmonary disease can occur without pulmonary involvement (but rare)

Hematologic

• Lymphocytopenia, anemia of chronic disease
• Pancytopenia (granulomatous infiltration of bone marrow)
• Splenic sequestration → thrombocytopenia, leukopenia

CVS

• Conduction defects, arrhythmias, heart failure

Nervous System

• Facial nerve palsy (most common neurological manifestation)
• Seizures, meningitis, peripheral neuropathy, psychiatric symptoms

GIT

• Hepatosplenomegaly (common)
• Parotid involvement → bilateral swelling
• Pancreas can be involved

Skin

• Papules, nodules, erythema nodosum, infiltration of old scars, lupus pernio

Eye

• Anterior or posterior uveitis, conjunctival involvement, papilledema
• Heerfordt's syndrome (Uveoparotid fever): anterior uveitis + parotid gland enlargement + fever + facial palsy

Musculoskeletal

• Effusion into joints, myalgia, arthralgia

Endocrine

• Diabetes insipidus (hypothalamus lesions)
• Diabetes mellitus (pancreas)
• Hypopituitarism, hypothyroidism

---

6. INVESTIGATIONS

---

7. TREATMENT

When to treat?

• Symptomatic disease
• Organ dysfunction: ocular, cardiac, CNS, severe pulmonary
• Hypercalcemia
• ⚠️ Intrathoracic lymph node involvement - does NOT need treatment
• Lung parenchymal involvement - needs treatment

Drugs

---

8. NATURAL HISTORY & PROGNOSIS

• Often self-limiting
• 2/3rd recover without treatment
• Progressive disease → disability from organ involvement
• Major cause of death: respiratory failure from interstitial lung disease

---

⭐ HIGH-YIELD EXAM POINTS (Kerala University)

1. Noncaseating granulomas - hallmark
2. Tuberculin test is NEGATIVE - important differentiator from TB
3. Gold standard = biopsy showing noncaseating granulomas
4. ACE + Calcium elevated - key lab findings
5. Facial nerve palsy = most common neurological manifestation
6. Heerfordt's syndrome = uveoparotid fever
7. Kveim test - historical, not used now
8. 2/3rd recover without treatment
9. Upper lobe > lower lobe lung involvement
10. Occurs in non-smokers

---

---

🦠 HANSEN'S DISEASE (LEPROSY) - Complete Study Notes

---

1. DEFINITION

• Chronic infectious disease caused by Mycobacterium leprae (or M. lepromatosis)
• Intracellular bacteria that parasitize macrophages and Schwann cells
• Characterized by granulomas and neurotropism
• Predilection for skin and peripheral nerves

---

2. EPIDEMIOLOGY

• WHO classifies it as a "neglected tropical disease"
• New cases fell from >500,000 (2003) → <150,000 (2021) due to multidrug therapy (MDT)
• Primarily seen in tropical/subtropical Asia, Africa, Central and South America
• Incidence remains relatively high in patients <15 years of age
• Named after Gerhard Henrik Armauer Hansen who identified M. leprae in the 1870s
• Mitsuda created the skin test in 1919; sulfones reported useful in 1942

---

3. PATHOGENESIS

Organism

• Very small, slightly curved acid-fast rods
• Obligate intracellular organisms
• Grow best at 27-33°C (prefer cooler body regions: nose, ear lobes, testes)
• Major sites: peripheral nerves, skin, mucous membranes, bones, viscera

Immunity & HLA

Immune Spectrum

• Tuberculoid (TT): Strong cell-mediated immunity (CMI), Th1 response, positive lepromin test, few bacilli
• Lepromatous (LL): Minimal CMI, Th2 response, negative lepromin test, increased humoral immunity, numerous bacilli

---

4. CLASSIFICATION

Ridley-Jopling Classification (1966) - Immunologic Basis

WHO Classification (Treatment-Based)

---

5. CLINICAL MANIFESTATIONS

General Features

• Primary skin lesion: erythematous or hypopigmented, often anesthetic
• Peripheral nerve involvement is a hallmark
• Most common cause of peripheral neuropathy in Southeast Asia, Africa, South America

Tuberculoid (TT) Leprosy

• Few (1-2) patches/plaques with sharply demarcated, raised borders
• Erythematous to hypopigmented
• Anesthesia / hypoesthesia (very characteristic)
• Unilateral neuropathic changes, digital resorption
• Pure neuritic leprosy = only neural involvement (no skin lesions)

Lepromatous (LL) Leprosy

• Multiple, poorly defined, erythematous macules, papules, nodules, plaques
• Widespread and symmetric distribution
• Sites: face, buttocks, extremities
• Leonine facies (forehead skin infiltration)
• Madarosis (loss of eyebrows/eyelashes)
• Saddle nose deformity
• Infiltration of both earlobes
• Acquired ichthyosis (lower extremities)
• Anesthesia in stocking-glove distribution
• Enlarged peripheral nerves
• Ocular: lagophthalmos (inability to fully close eyes), corneal anesthesia

Borderline (BB) Leprosy

• "Swiss cheese" annular plaques - characteristic!
• BT: asymmetric, larger lesions
• BL: numerous, symmetric, variable morphology
• Neuropathies most common in borderline leprosy

Special Forms

• Histoid leprosy: Dermatofibroma-like papules/nodules; variant of LL
• Lucio leprosy: Non-nodular, diffuse LL; caused by M. lepromatosis; seen in Mexico/Central America

Nerve Involvement

• Superficial cutaneous nerves of ears and distal limbs
• Mononeuropathy, multiple mononeuropathies, or symmetric sensorimotor polyneuropathy
• Commonly affected nerves:
  • Ulnar nerve (at elbow) → claw hand
  • Common peroneal → foot drop
  • Greater auricular, radial cutaneous, sural nerves - thickened/palpable
  • Facial nerve → lagophthalmos
  • Trigeminal → corneal anesthesia

---

6. LEPRA REACTIONS (Acute inflammatory episodes - occur in ~30-50% patients)

---

7. INVESTIGATIONS

---

8. TREATMENT

WHO MDT Regimen (2018 Guidelines) - 3 drugs for ALL patients

After first dose, patient is no longer infectious

US National Hansen Disease Program

• PB: 1 year; MB: 2 years
• Single lesion PB: ROM scheme - Rifampicin + Ofloxacin + Minocycline (single dose option)

Reactions Treatment

• Type 1 (Reversal): Oral prednisone
• Type 2 (ENL): Thalidomide (principal therapy) ± corticosteroids
• Lucio phenomenon: Systemic corticosteroids

Drug Resistance

• Rifampicin resistance: mutation in rpoB gene
• Dapsone resistance: mutation in folp1 gene

---

9. DISABILITY GRADING (WHO)

---

⭐ HIGH-YIELD EXAM POINTS (Kerala University)

1. Causative organism: Mycobacterium leprae (acid-fast, obligate intracellular)
2. Grows at 27-33°C → prefers cool areas (nose, ear lobes, testes)
3. Tuberculoid: few lesions, well-defined, anesthetic, strong CMI, Th1, Mitsuda positive
4. Lepromatous: multiple symmetric lesions, Th2, Mitsuda negative, leonine facies, madarosis, saddle nose
5. Borderline = highest risk for lepra reactions; "Swiss cheese" in BB
6. Gold standard: skin biopsy - noncaseating granulomas (TT) vs foamy macrophages + bacilli (LL)
7. Fite stain for bacilli
8. Mitsuda test = PROGNOSTIC (not diagnostic)
9. Type 1 reaction → borderline → treat with steroids
10. Type 2 (ENL) → lepromatous → treat with thalidomide
11. MDT = Rifampicin + Dapsone + Clofazimine (WHO 2018: 3 drugs for all)
12. PB = 6 months; MB = 12 months
13. Not infectious after first dose of MDT
14. False-positive VDRL, ANA in lepromatous leprosy
15. Most common peripheral neuropathy in SE Asia = leprosy

---