First Salvini, now Johnson, have been betrayed by their female companions.
On Monday evening the Prime Minister offered Mr Cain the vacant job of Downing Street chief of staff.
Who else could follow Cummings out the door?
Many of the most senior figures in Downing Street owe their loyalty to Dominic Cummings from Vote Leave days.
Lee Cain's resignation on Wednesday night had already caused deep frustration.
And there are fears that some could follow Mr Cummings out of the door now he has signalled his departure.
They include advisers Cleo Watson, Oliver Lewis - known as 'Sonic' - and data guru Ben Warner.
A source has said that while Brexit envoy Lord Frost was unhappy about Mr Cain's departure, he has no intention of quitting as talks with Brussels enter their final stages.
The move was backed by both Mr Cummings and the Cabinet Secretary, Simon Case, who argued that Mr Cain had been fulfilling part of the role for months.
However, news of the appointment was leaked to the Mail – prompting a furious backlash from senior Tories, who feared it would further embolden a Vote Leave faction contemptuous of the role of MPs.
Crucially, it also encountered the wrath of Ms Symonds, who dislikes Mr Cain's abrasive style. She told her fiancé it would be a 'mistake' to give him a promotion.
As news of the row behind the scenes became public, Mr Cain decided his role was untenable.
He will stay in post until the end of the year, when he will be replaced as director of communications by former Mail journalist James Slack, currently Mr Johnson's official spokesman. However, unlike Mr Cain, who was a political appointment, he will remain a civil servant.
Tory MPs warned Mr Johnson that the chaos in No 10 was undermining public confidence in the Government.
Sir Roger Gale said it was 'extraordinary and unacceptable that Downing Street should allow itself to be distracted by internal squabbles' in the midst of a pandemic.
He added: 'Frankly this is a distraction... the Prime Minister has got to get a grip on it.'
Other MPs urged Mr Johnson to ditch his special adviser.
One said: 'If they have got rid of one of the Kray brothers they have got to get rid of Cummings as well. To use a well-known phrase, Boris should take back control and be the real Boris that so many of his genuine friends and supporters believe he can be.'
The Prime Minister also faced questions over Ms Symonds' role in Downing Street.
'The question on everyone's lips is ''who will she go after next''... it looks like senior appointments now have to be approved by Carrie,' an insider said.
'That is a dangerous path for the Government to go down.'
Another adviser said the episode reflected poorly on the Prime Minister. 'It is disappointing that he has failed to return the loyalty of his most loyal lieutenant when the going got tough,' they said.
'It begs the question – who is making the decisions now?'
Looks like Britain has a new Lady Macbeth in the making. Boris Johnson actually looks afraid of her. Once again, the foolishness of placing any confidence in a "leader" who can't stop chasing women is underlined.
UPDATE: And now Johnson's best adviser has exited the sinking ship.
Boris Johnson's chief adviser Dominic Cummings has left Number 10 with immediate effect, BBC political editor Laura Kuenssberg says. Mr Cummings spoke to the PM earlier on Friday and it was decided it was best for him to go immediately after days of turmoil, our political editor said.