A 43 y.o. with a hx of drug use comes to the ED complaining of sores in his mouth and skin lesions.

What could this be?

Our patient had pemphigus vulgaris which is an IgG related autoimmune disease that cause wide spread blisters on the skin and mucous membranes. Autoantibodies are formed against desmosome proteins of keratinocytes in the epidermis.  This happens either by direct antibody production or biochemical induction of cytokines.

Drugs are the leading cause of pemphigus.( Spoiler alert: the next paragraph contains chemistry.)

The most common drug groups causing pemphigus are thiols and phenols. Thiol drugs contain a sulfhydryl group(-SH) Captopril and penicillamine are in this group and can induce production of cytokines. Phenols(C6H6O) are aromatic organic compounds with a phenyl group( a six carbon ring) and a hydroxyl group(OH)    The most common phenols involved include aspirin, heroin, rifampin and levodopa. 

There may be a genetic predisposition to pemphigus in people of Jewish or  Mediterranean descent.

Clinically pemphigus can mimic lichen planus, Stevens Johnson syndrome  or staphylococcal scalded skin syndrome.

Cocaine induced pemphigus

Causes of pemphigus vulgaris  include :

Paraneoplastic syndromes-this is a rare cause of pemphigus associated with 90% mortality. Lymphomas, sarcomas, squamous cell cancers, lung and colon cancers have been implicated.

Drug related – cocaine, captopril, levodopa, cephalosporins, interferon, sulfa,  propranolol  rifampin,  NSAIDS and vaccines

Infection related- Hep C, herpes simplex, Epstein-Barr virus, CMV

PEMPHIGOID

Pemphigoid also presents with a blistering rash but since the autoimmune reaction is subepidermal; the deeper blisters are less fragile. The Nicolsky sign differentiates pemphigus from pemphigoid.  If lateral pressure is placed on a blister, the blister extends along the surface when the autoimmune reaction is in the epidermis.  This sign  is present in pemphigus, TEN, and Staphylococcal scalded skin syndrome.

INTERESTING FACT

While cocaine has been shown to cause pemphigus be aware that all “cocaine” does not actually contain cocaine. Liam Payne’s death was caused by pink cocaine. Pink cocaine or Tusi comes in the form of a pink powder.  It contains several drugs including MDMA, ketamine, caffeine and 2-CB, a psychedelic drug (4-bromo-2,5-dimethoxyphenethylamine)  It does not contain cocaine.

pink cocaine

Our patient was HepC positive . He was also positive for cocaine.   He was  treated with steroids and his lesions resolved.  It was not clear if the pemphigus was related to his hep C or his drug use.

Jimenez-Zarazua O, Guzman-Ramirez A, Velez-Ramirez L, et al. A case of acute pemphigus vulgaris relapses associated with cocaine use and review of the literature.  Dermatol Ther 2018 Nov 10;8(4):653-663.

Kasperkiewicz M, Ellebrecht C, Takahashi H, et al. Pemphigus. Nat rev Dis Primers 2017 May 11;3:17026

Kelly S, Schifter M, Fulcher D, Lin M. Praneoplastic pemphigus: two cases of intra-abdominal syndrome 20 years after. Int J Dermatol. 2011 Aug: 50(8):905-14.

Akel R, Fakhri G, Salem R, Boulos F, Habib K, Tfayli A. Paraneoplastic Pemphigus as a First Manifestation of an Intra-Abdominal Follicular Dendritic Cell Sarcoma: Rare Case and Review of the Literature. Case Rep Oncol. 2018 May-Aug;11(2):353-359.

Pile H, yarrarapu, Crane J.  Drug induced pemphigus. Stat Pearls 2024 https://www.ncbi.nlm.nih.gov/books/NBK499864/