6.3 Common Dermatological & Psychiatric Manifestations in Internal Medicine
Key Takeaways
- Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) represent a spectrum of severe mucocutaneous reactions defined by total body surface area (TBSA) of epidermal detachment: SJS < 10%, SJS/TEN overlap 10–30%, and TEN > 30%, exhibiting a positive Nikolsky sign.
- Erythema Nodosum is a septal panniculitis presenting as painful, tender erythematous nodules on the anterior shins; it is a major cutaneous marker for Sarcoidosis (Löfgren syndrome), Tuberculosis, Streptococcal infection, and Inflammatory Bowel Disease.
- Delirium is an acute, fluctuating disturbance of attention and level of consciousness caused by underlying organic medical conditions, distinguishing it from Dementia which is characterized by chronic, progressive cognitive decline with preserved consciousness.
- Neuroleptic Malignant Syndrome (NMS) is caused by dopamine D2 receptor blockade, featuring hyperthermia, severe "lead-pipe" muscle rigidity, autonomic instability, and extreme Creatine Kinase (CK) elevation, treated with Dantrolene or Bromocriptine.
- Serotonin Syndrome is triggered by excessive serotonergic activity and is clinically differentiated from NMS by hyperreflexia, ocular/inducible clonus, hyperactive bowel sounds, and rapid onset (< 24 hours), managed with Cyproheptadine.
Common Dermatological & Psychiatric Manifestations in Internal Medicine
Cutaneous markers of systemic disease and acute neuropsychiatric emergencies frequently appear on UPSC CMS examination papers. Mastering severe cutaneous adverse reactions, systemic dermatoses, delirium, and life-threatening toxidromes like Neuroleptic Malignant Syndrome and Serotonin Syndrome is essential for clinical practice and board examinations.
1. Severe Cutaneous Adverse Reactions (SCARs): SJS & TEN
Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) represent life-threatening, cell-mediated, cytotoxic hypersensitivity reactions characterized by widespread destruction and detachment of the epidermis and mucosal membranes.
Pathophysiology
Triggered predominantly by drugs, cytotoxic T-lymphocytes (CD8+) and natural killer (NK) cells induce massive keratinocyte apoptosis through two primary pathways:
- Granulysin (a key cytotoxic protein secreted in blister fluid — single most important mediator).
- Fas - Fas Ligand (FasL) interactions and Perforin/Granzyme B pathway.
Disease Spectrum & Staging
The distinction between SJS and TEN is based strictly on the percentage of Total Body Surface Area (TBSA) exhibiting epidermal detachment:
| Condition | TBSA Epidermal Detachment | Mucosa Involved | Mortality Rate |
|---|---|---|---|
| Stevens-Johnson Syndrome (SJS) | < 10% TBSA | ≥ 2 mucosal sites (90%) | 1% – 5% |
| SJS / TEN Overlap | 10% – 30% TBSA | ≥ 2 mucosal sites (100%) | 10% – 15% |
| Toxic Epidermal Necrolysis (TEN) | > 30% TBSA | Severe involvement of multiple sites | 25% – 50% |
High-Risk Offending Drugs (Mnemonic: SATAN)
- S: Sulfonamides (Cotrimoxazole / Trimethoprim-Sulfamethoxazole, Sulfasalazine)
- A: Antiepileptics (Carbamazepine, Phenytoin, Lamotrigine, Phenobarbital)
- T: Toxic NSAIDs (Oxicams: Piroxicam, Meloxicam)
- A: Allopurinol (especially in patients with renal impairment or HLA-B*5801 allele)
- N: Nevirapine (NNRTI) / Non-nucleoside reverse transcriptase inhibitors
Clinical Features & Characteristic Signs
- Prodrome: High-grade fever, malaise, sore throat, and conjunctivitis preceding skin lesions by 1 to 3 days.
- Cutaneous Lesions: Dusky erythematous macules, targetoid atypical papules, coalescing into flaccid bullae that rupture, leaving extensive denuded, scalded-appearing dermis.
- Mucosal Involvement: Severe erosions of ocular (purulent conjunctivitis, corneal ulceration, symblepharon), oral (crusted hemorrhagic lips, painful stomatitis), and anogenital mucosa.
- Physical Signs:
- Nikolsky Sign: Positive (dislodgement of intact superficial epidermis by light lateral sliding manual pressure on unblistered skin).
- Asboe-Hansen Sign: Positive (extension of a bulla laterally into unblistered skin when direct vertical pressure is applied to the roof of the bulla).
Management Protocol
- Immediate Withdrawal: Stop all non-essential and potentially culprit medications instantly.
- Supportive Care: Transfer to a Specialized Burn Unit or ICU. Maintain room temperature at 30–32°C.
- Fluid & Electrolyte Balance: Warmed Ringer's Lactate (calcified using modified Parkland formula; fluid requirements are typically 2/3 of thermal burn requirements due to less edema).
- Ophthalmologic Care: Daily examination by an ophthalmologist; lubricating eye drops, topical antibiotic drops, and breaking of synechiae to prevent permanent blindness and symblepharon.
- Specific Immunomodulatory Therapy: Cyclosporine (3–5 mg/kg/day), High-dose IVIG (Intravenous Immunoglobulin 1 g/kg/day for 3 days), or Plasma Exchange (Plasmapheresis). Prophylactic systemic antibiotics are NOT recommended.
2. Cutaneous Markers of Systemic Internal Diseases
A. Erythema Nodosum (EN)
Erythema Nodosum is a hypersensitivity reaction involving the subcutaneous fat (septal panniculitis without vasculitis).
- Clinical Presentation: Painful, tender, warm, erythematous, non-ulcerating nodules situated symmetrically over the anterior shins (tibial surfaces). Lesions evolve over 2–8 weeks like a bruise (changing from red/purple to yellowish-green / erythema contusiformis).
- Major Systemic Etiologies (Mnemonic: SHINS):
- S: Sarcoidosis (Löfgren Syndrome triad: Erythema Nodosum + Bilateral Hilar Lymphadenopathy + Acute Polyarthralgia).
- H: Histoplasmosis / Fungal infections.
- I: Infections (Streptococcal pharyngitis - most common cause in children; Primary Tuberculosis; Leprosy - Erythema Nodosum Leprosum / ENL Type 2 reaction).
- N: No cause identified (Idiopathic in up to 50% of cases).
- S: Systemic Inflammatory Bowel Disease (Ulcerative Colitis & Crohn's Disease) / Sulfonamides & Oral Contraceptive Pills.
B. Other High-Yield Cutaneous Manifestations
| Cutaneous Condition | Morphological Features | Associated Systemic Disease |
|---|---|---|
| Acanthosis Nigricans | Hyperpigmented, velvety, hyperkeratotic plaques in intertriginous areas (neck, axillae, groin) | Insulin Resistance (Type 2 DM, PCOS, Obesity); Gastrointestinal Malignancy (Gastric Adenocarcinoma - if rapid onset / tripe palms) |
| Pyoderma Gangrenosum | Extremely painful, rapidly enlarging ulcer with purplish/violaceous, undermined, rolled edges; exhibits pathergy | Inflammatory Bowel Disease (Ulcerative Colitis > Crohn's), Rheumatoid Arthritis, Acute Myeloid Leukemia |
| Erythema Multiforme (EM) | Typical targetoid lesions (3 concentric rings: central dusky blister, pale edematous zone, outer erythematous ring) | Infections: Herpes Simplex Virus (HSV 1 & 2) (90% of cases), Mycoplasma pneumoniae |
| Erythema Gyratum Repens | Wood-grain pattern of concentric erythematous rings with fine trailing scale, rapidly migrating | Malignancy (Paraneoplastic marker: Bronchogenic Carcinoma, Esophageal Carcinoma) |
3. Delirium vs. Dementia in General Hospital Wards
Distinguishing acute Delirium from Dementia is one of the most critical bedside skills in internal medicine wards.
Differential Features Matrix
| Diagnostic Feature | Delirium (Acute Confusional State) | Dementia (Major Neurocognitive Disorder) |
|---|---|---|
| Onset | Acute (hours to days) | Insidious (months to years) |
| Course | Fluctuating over 24 hours (lucid intervals, evening worsening / "sundowning") | Progressive, stable day-to-day decline |
| Consciousness / Alertness | Impaired / Altered (reduced, hyperalert, or lethargic) | Intact until very late stages |
| Attention | Severely Impaired (inability to focus, sustain, or shift attention) | Relatively intact in early/moderate stages |
| Memory | Immediate & short-term memory impaired secondary to inattention | Short-term memory severely impaired early; remote memory lost late |
| Perception | Frequent visual hallucinations and illusions | Hallucinations absent until late stages (except DLB) |
| Reversibility | Potentially Reversible once underlying cause is treated | Usually Irreversible (progressive neurodegeneration) |
Common Precipitating Causes of Delirium (Mnemonic: DELIRIUMS)
- D: Drugs (Anticholinergics, Benzodiazepines, Sedatives, Opioids, Steroids, Polypharmacy).
- E: Electrolyte Imbalance (Hyponatremia, Hypercalcemia, Hypomagnesemia).
- L: Lack of drugs (Alcohol or Benzodiazepine Withdrawal).
- I: Infection (Urinary Tract Infection, Pneumonia, Meningitis, Sepsis).
- R: Reduced sensory input / Retention (Urinary retention, Severe constipation).
- I: Intracranial pathology (Acute Ischemic Stroke, Subdural Hematoma, Encephalopathy).
- U: Uremia / Hepatic Failure / Hypoxia.
- M: Metabolic disturbances (Hypoglycemia, Diabetic Ketoacidosis, Thyroid storm).
- S: Sleep deprivation / Post-operative state.
4. Neuroleptic Malignant Syndrome (NMS) vs. Serotonin Syndrome
Both NMS and Serotonin Syndrome are life-threatening, drug-induced hyperthermic emergencies encountered in medical and psychiatric wards. A precise distinction is vital because their pharmacological treatments differ completely.
Comprehensive Comparison Matrix
| Clinical Parameter | Neuroleptic Malignant Syndrome (NMS) | Serotonin Syndrome |
|---|---|---|
| Etiology | Dopamine D2 receptor blockade or abrupt withdrawal of dopamine agonists (Levodopa) | Excessive central and peripheral serotonergic neurotransmission (5-HT1A / 5-HT2A) |
| Causal Agents | Typical Antipsychotics (Haloperidol, Fluphenazine), Atypical Antipsychotics (Olanzapine, Risperidone), Metoclopramide | SSRIs, SNRIs, MAOIs, TCAs, Tramadol, Linezolid, Fentanyl, MDMA ("Ecstasy"), St. John's Wort |
| Onset | Subacute / Slow (develops over 1 to 3 days or weeks after drug initiation/dose escalation) | Rapid / Acute (develops within 6 to 24 hours of drug initiation or combination) |
| Neuromuscular Signs | Severe generalized "Lead-pipe" Rigidity, bradykinesia, hyporeflexia | Hyperreflexia, Clonus (spontaneous, inducible, or ocular clonus), Tremor, Akathisia (Legs > Arms) |
| Gastrointestinal | Bowel sounds normal or decreased; no diarrhea | Hyperactive bowel sounds, abdominal cramps, profuse diarrhea |
| Pupils | Normal or sluggish | Mydriasis (dilated pupils), diaphoresis |
| Temperature | Extreme Hyperthermia (often > 40°C / 104°F) | Hyperthermia (mild to severe depending on toxicity) |
| Laboratory Profile | Marked elevation of Creatine Kinase (CK) (> 1,000–10,000+ U/L), Leukocytosis (10,000–40,000/mm³), Myoglobinuria | Normal or mildly elevated CK; normal WBC |
| Specific Antidote | Dantrolene (IV skeletal muscle relaxant) AND Bromocriptine / Amantadine (Dopamine agonist) | Cyproheptadine (Oral 5-HT1A / 5-HT2A receptor antagonist) |
Emergency Management Guidelines
- NMS Management:
- Immediately discontinue all causative antipsychotic agents.
- Initiate aggressive external cooling (cooling blankets, ice packs in axillae/groin) and IV fluid hydration to prevent renal failure from rhabdomyolysis.
- Administer Dantrolene (1 to 2.5 mg/kg IV bolus, max 10 mg/kg/day) to reduce muscle rigidity and heat generation.
- Administer Bromocriptine (2.5 to 5 mg orally/NG tube every 8 hours) to restore central dopaminergic tone.
- Serotonin Syndrome Management:
- Immediately discontinue all serotonergic agents.
- Provide supportive care and IV Benzodiazepines (Diazepam 5–10 mg IV) to control agitation, seizures, and muscle twitching.
- Administer Cyproheptadine (Initial dose: 12 mg orally/NG tube, followed by 2 mg every 2 hours if symptoms persist; maintenance 4–8 mg q6h).
A 42-year-old male treated with Cotrimoxazole for a urinary tract infection develops high fever, conjunctival redness, painful oral mucosal erosions, and widespread flaccid skin bullae. On physical examination, skin detachment covers 35% of his total body surface area (TBSA), and gentle lateral pressure on unaffected skin causes epidermal sloughing (positive Nikolsky sign). What is the definitive diagnosis?
A 26-year-old female presents with a 2-week history of tender, warm, erythematous nodules over both anterior shins, accompanied by ankle arthralgias and fever. Chest X-ray reveals bilateral hilar lymphadenopathy without parenchymal infiltrates. What is the diagnosis and characteristic histopathological finding of these cutaneous lesions?
A 74-year-old hospitalized patient on day 3 post-hip replacement surgery becomes acutely agitated, disoriented to time and place, and reports seeing insects crawling on the wall. His clinical symptoms fluctuate significantly throughout the day, with lucid intervals during the morning and severe worsening in the evening. Which single feature most reliably distinguishes Delirium from Dementia?
A 38-year-old psychiatric inpatient on high-dose Haloperidol develops a temperature of 40.2°C, extreme generalized "lead-pipe" muscle rigidity, diaphoresis, fluctuating blood pressure, and confusion. Serum lab testing reveals a Creatine Kinase (CK) level of 18,500 U/L and severe leukocytosis. What is the specific pharmacological antidote of choice for this condition?